Neurological complications of infection by the mosquito-borne Zika virus (ZIKV) include Guillain-Barré syndrome (GBS), an acute inflammatory demyelinating polyneuritis. GBS was first associated with recent ZIKV epidemics caused by the emergence of ZIKV Asian lineage in South Pacific. Here, we hypothesize that ZIKV-associated GBS relates to a molecular mimicry between viral envelope E (E) protein and neural proteins involved in GBS. Analysis of ZIKV epidemic strains showed that glycan loop (GL) region of the E protein includes an IVNDT motif which is conserved in voltage-dependent L-type calcium channel subunit alpha-1C (Cav1.2) and Heat Shock 70 kDa protein 12A (HSP70 12A). Both VSCC-alpha 1C and HSP70 12A belong to protein families which have been associated with neurological autoimmune diseases in central nervous system. The purpose of our in silico analysis is to point out that IVNDT motif of ZIKV E-GL region should be taken in consideration for the development of safe and effective anti-Zika vaccines by precluding the possibility of adverse neurologic events including autoimmune diseases such as GBS.

Background: COVID-19 booster uptake remained poor among healthcare workers (HCW) despite evidence of improved immunity against Delta and Omicron variants. While most studies used a questionnaire to assess hesitancy, this study aimed to identify factors affecting true booster hesitancy by examining actual vaccine uptake across time. Method: COVID-19 vaccination database records among HCW working at 7 Singaporean public primary care clinics between January to December 2021 were extracted, with gender, profession, place of practice, vaccination type and dates. Time to booster was calculated from the date of vaccination minus date of eligibility. Chi-square test was used to compare relationship between 1st dose and booster hesitancy, Kaplan-Meier method and Log-rank test were adopted to evaluate differences in cumulative booster uptake. Multivariate cox regression was used to investigate predictors for timely booster vaccination. Vaccination rate was charted across time and corroborated with media releases pertaining to legislative changes. Results: 877 of 891 (98.9%) primary care HCW were fully vaccinated, 73.8% of eligible HCW had taken the booster. HCW were less booster hesitant [median 16 (5-31.3) days] compared to the 1st dose [median 39 (13-119.3) days]. 1st dose hesitant HCW were more likely to be booster hesitant (OR=3.66, 95%CI 2.61-5.14). Adjusting for sex, workplace and time to 1st dose, ancillary (HR=1.53, 95%CI 1.03-2.28), medical (HR=1.8, 95%CI 1.18-2.74) and nursing (HR=1.8, 95%CI 1.18-2.37) received boosters earlier compared with administrative staff. No temporal relationship was observed between booster uptake, legislative changes and COVID-19 infection numbers. Conclusion: Vaccine hesitancy among HCW had improved from booster to 1st dose, with timely booster vaccination among medical and nursing staff. Tailored education, risk messaging and strategic legislation might help to reduce delayed booster vaccination.

Despite the remarkable success of SARS CoV-2 vaccines, the rise of variants, some of which are more resistant to the effects of vaccination, highlights the potential need for additional COVID-19 vaccines. We used the Multiple Antigen Presenting System (MAPS) technology, in which proteins are presented on a polysaccharide polymer to induce antibody, Th1, Th17 and CD8+ T cell responses, to engineer a novel vaccine targeting SARS CoV-2. This vaccine contains a fragment of the spike (S) protein receptor-binding domain (RBD) sequence of the original D614G strain and was used to immunize nonhuman primates (NHP) for assessment of immunological responses and protection against SARS CoV-2 challenge. The SARS CoV-2 MAPS vaccine generated robust neutralizing antibodies as well as Th1, Th17 and cytotoxic CD8 T-cell responses in NHPs. Furthermore, MAPS-immunized NHPs had significantly lower viral loads in the nasopharynx and lung compared to control animals. Taken together, these findings support the use of the MAPS platform to make a SARS CoV-2 vaccine. The nature of the platform also could enable its use for the inclusion of different variants in a single vaccine.

The novel coronavirus disease (COVID-19) has created immense threats to public health on various levels around the globe. The unpredictable outbreak of this disease and the pandemic situation are causing severe depression, anxiety and other mental as physical health related problems among the human beings. To combat against this disease, vaccination is essential as it will boost the immune system of human beings while being in the contact with the infected people. The vaccination process is thus necessary to confront the outbreak of COVID-19. This deadly disease has put social, economic condition of the entire world into an enormous challenge. The worldwide vaccination progress should be tracked to identify how fast the entire economic as well as social life will be stabilized. The monitor ofthe vaccination progress, a machine learning based Regressor model is approached in this study. This tracking process has been applied on the data starting from 14^th December, 2020 to 24^th April, 2021. A couple of ensemble based machine learning Regressor models such as Random Forest, Extra Trees, Gradient Boosting, AdaBoost and Extreme Gradient Boosting are implemented and their predictive performance are compared. The comparative study reveals that the AdaBoostRegressor outperforms with minimized mean absolute error (MAE) of 9.968 and root mean squared error (RMSE) of 11.133.

Eastern (EEEV) and Venezuelan (VEEV) equine encephalitis viruses (EEVs) are related, (+)ssRNA arboviruses that can cause severe, sometimes fatal, encephalitis in humans. EEVs are highly infectious when aerosolized, raising concerns for potential use as biological weapons. No licensed medical countermeasures exist; given the severity/rarity of natural EEV infections, efficacy studies require animal models. Cynomolgus macaques exposed to EEV aerosols develop fever, encephalitis, and other clinical signs similar to humans. Fever is nonspecific for encephalitis in macaques. Electrocardiography (ECG) metrics may predict onset, severity, or outcome of EEV-attributable disease. Macaques were implanted with thermometry/ECG radiotransmitters and exposed to aerosolized EEV. Data was collected continuously, and repeated-measures ANOVA and frequency-spectrum analyses identified differences between courses of illness and between pre-exposure and post-exposure states. EEEV-infected macaques manifested widened QRS-intervals in severely ill subjects post-exposure. Moreover, QT-intervals and RR-intervals decreased during the febrile period. VEEV-infected macaques suffered decreased QT-intervals and RR-intervals with fever onset. Frequency-spectrum analyses revealed differences in the fundamental frequencies of multiple metrics in the post-exposure and febrile periods compared to baseline and confirmed circadian dysfunction. Heart rate variability (HRV) analyses revealed diminished variability post-exposure. These analyses support using ECG data alongside fever and clinical laboratory findings for evaluating medical countermeasure efficacy.

mRNA vaccines have attracted widespread research attention with clear advantages in terms of molecular flexibility, rapid development, and potential for personalization. However, current mRNA vaccine platforms have not been optimized for induction of CD4/CD8 T cell responses. In addition, mucosal administration of mRNA based on lipid nanoparticle technology faces challenges in clinical translation. In contrast, adenovirus-based vaccines induce strong T-cell responses and have been approved for intranasal delivery. To leverage the inherent strengths of both the mRNA and adenovirus platforms, we developed a novel modular adenoviral mRNA delivery platform based on Tag/Catcher bioconjugation. Specifically, we engineered adenoviral vectors integrating Tag/Catcher proteins at specific locales on the Ad capsid proteins, allowing us to anchor mRNA to the surface of engineered Ad viruses. In proof-of-concept studies, the Ad-mRNA platform successfully mediated mRNA delivery and could be optimized via the highly flexible modular design of both the Ad-mRNA and protein bioconjugation systems.

The novel coronavirus (COVID-19) was first reported in the U.S. on December 29, 2019 and has spread rapidly throughout the country, affecting individuals with varying severity due to their risk status. According to the Centers for Disease Control and Prevention, it is estimated that 45.4% of US adults are at higher risk for complications from coronavirus disease because of cardiovascular disease, diabetes, respiratory disease, hypertension, or cancer. In this study, we developed a mathematical model to assess the impact of a COVID-19 vaccine among low and high risk groups. Numerical simulations shows vaccinating both low and high risk groups simultaneously, rather than prioritizing the vaccine on high risk group only, further reduces the daily mortality. The result supports the need for an aggressive vaccination program, regardless of whether individuals are within the low or high risk population.

Despite the research conducted worldwide, there is no treatment specific for SARS-CoV-2 infection with efficacy proven by randomized controlled trials. A chance for a breakthrough is vaccinating the majority of the global population. The public opinion surveys on vaccine hesitancy prompted our team to investigate the Polish medical community's attitude towards the SARS-CoV-2 and influenza vaccinations. In-person and online surveys of Healthcare Workers (HCWs): doctors, nurses, medical students, and other allied health professionals (n=419) took place between 14.09.2020 and 5.11.2020. In our study, 68.7% of respondents would like to be vaccinated with the COVID-19 vaccine. The safety and efficacy of vaccination against COVID-19 would persuade 86.3% of hesitant and those who would refuse to be vaccinated. 3.1% of all respondents claimed that no argument would convince them to get vaccinated. 61.6% of respondents declared a willingness to receive an influenza vaccination, of which 83.3% were also inclined to receive the planned COVID-19 vaccination. Although a significant part of respondents - 62.5% (262/419) indicated, they trusted the influenza vaccine more than the COVID-19 vaccine in direct comparison, more respondents intended to get the COVID-19 vaccination than the influenza vaccine in the 2020/2021 season.

The adverse relationship between viral hepatitis and pregnancy in developing countries was seen as a reflection of retrospective biased hospital-based data collection by the West. However, the discovery of HEV from an epidemic of non-A, non-B hepatitis in Kashmir and documenting increased incidence and severity of hepatitis E in pregnancy from a house-to-house survey unmasked the unholy alliance. Among the family of HEV’s, genotype (gt)-1, with a unique ORF4-encoded protein enhancing viral polymerase activity and viral replication, is the sole HEV that shows this adverse relationship. The epidemics caused by HEV-gt1 and not by HEV-gt2 show adverse relationship with pregnancy. The pathogenesis of the unholy alliance is complex and at present not well understood. Possibly multiple factors play a role in causing severe liver disease in the mother including: infection, replication and damage to the maternal-foetal interface by HEV-gt1; vertical transmission of HEV to foetus causing severe foetal/neonatal hepatitis; and combined viral and hormone related immune dysfunction of diverse nature in the mother promoting viral replication. Management is multidisciplinary and needs a close watch for the development and management of ALF. Preliminary data suggest beneficial maternal outcomes by early termination of pregnancy in patients with lower grades of encephalopathy.

Vaccination remains an important mitigation tool against COVID-19. We report 1-month safety and preliminary immunogenicity data from a substudy of an ongoing, open-label, phase 2/3 study of monovalent Omicron XBB.1.5-adapted BNT162b2 (single 30-μg dose). Healthy, participants ≥12 years old (N=412 [12‒17 years, N=30; 18‒55 years, N=174; >55 years, N=208]) who previously received ≥3 doses of a US-authorized mRNA vaccine, the most recent being an Omicron BA.4/BA.5-adapted bivalent vaccine ≥150 days before study vaccination, were vaccinated. Serum 50% neutralizing titers against Omicron XBB.1.5, EG.5.1, and BA.2.86 were measured 7 days and 1 month after vaccination in a subset of ≥18-year-olds (N=40) who were positive for SARS-CoV-2 at baseline. Seven-day immunogenicity was also evaluated in a matched group who received bivalent BA.4/BA.5-adapted BNT162b2 in a previous study (NCT05472038). There were no new safety signals; local reactions and systemic events were mostly mild to moderate in severity, adverse events were infrequent, and none led to study withdrawal. The XBB.1.5-adapted BNT162b2 induced numerically higher titers against Omicron XBB.1.5, EG.5.1, and BA.2.86 than BA.4/BA.5-adapted BNT162b2 at 7 days and robust neutralizing responses to all 3 sublineages at 1 month. These data support a favorable benefit-risk profile of XBB.1.5-adapted BNT162b2 30 μg. NCT05997290

Introduction: The top priority of active immunoprophylaxis of pertussis is immunisation of infants as they can develop severe multiple-organ complications or even die from this disease. Objectives: The aim of the work is the identification of factors negatively affecting vaccine immunity to pertussis in preschool children prior to the administration of the first booster. Patients and Methods: The research was conducted on 352 children from 4.5 to 5.9 years of age who were hospitalised in the University Children’s Hospital in Lublin (Poland) from 1 January 2012 to 31 December 2015. The children taking part in the study had been administered all the mandatory vaccines from their birth to the age of 2 or 2.5 years old according to the Polish Immunisation Program 2008-2009. The immunoenzymatic method ELISA was applied to assess vaccine immunity to tetanus, diphtheria, pertussis, Haemophilus influenzae type b (Hib), poliomyelitis (IPV), mumps, rubella and measles. The level of vaccine antibodies to hepatitis type B was determined chemilumiscently. Results: The protective antibody titer was not found in 41 (11.65%) children before the administration of the booster. To verify the collective impact of parameters analised on antibody titer to pertussis, the Generalized Linear Model (GLZ) was used. Gender, type of vaccine, asthma, Hib and mumps antibody titers have been shown to be predicators of vaccine immunity to pertussis. Conclusions: Immunomodulation considered on the example of titer of IgG antibody to pertussis can serve as a useful model of the assessment of development of acquired immunity after mandatory vaccinations.

As the number of infections and deaths caused by the recent COVID-19 pandemic is increasing dramatically day-by-day, scientists are rushing towards developing possible counter-measures to fight the deadly virus, SARS-CoV-2. Although many efforts have already been put forward for designing and developing potential vaccines, however, most of them are proved to possess negative consequences. Therefore, in this study, the methods of immunoinformatics were exploited to design novel epitope-based subunit vaccine against the SARS-CoV-2, targeting four essential proteins of the virus i.e., spike glycoprotein, nucleocapsid phosphoprotein, membrane glycoprotein, and envelope protein. The highly antigenic, non-allergenic, non-toxic, non-human homolog and 100% conserved (across other isolates from different regions of the world) epitopes were used for constructing the vaccine. In total, fourteen CTL epitopes and eighteen HTL epitopes were used to construct the vaccine. Thereafter, several in silico validations i.e., the molecular docking, molecular dynamics simulation (including the RMSF and RMSD studies), and immune simulation studies were also performed which predicted that the designed vaccine should be quite safe, effective, and stable within the biological environment. Finally, in silico cloning and codon adaptation studies were also conducted to design an effective mass production strategy of the vaccine. However, more in vivo and in vitro studies are required on the predicted vaccine to finally validate its safety and efficacy.

The human antibody response to influenza virus infection or vaccination is as complicated as it is essential for protection against flu. The constant antigenic changes of the virus to escape human herd immunity hinder the yearly selection of vaccine strains since it is hard to predict which virus strains will circulate for the coming flu season. A "universal" influenza vaccine that could induce broad cross-influenza subtype protection would help to alleviate this burden. However, the human antibody response is intricate and often obscure, with factors like antigenic seniority or original antigenic sin "OAS", and back-boosting ensuring that each person mounts a unique immune response to infection or vaccination with any new influenza virus strain. Notably, the effects of existing antibodies on cross-protective immunity after repeated vaccinations are unclear. More research is needed to characterize the mechanisms at play, but traditional assays such as hemagglutinin inhibition (HAI) and microneutralization (MN) are excessively limited in scope and too resource-intensive to effectively meet this challenge. In the past ten years, new multiple dimensional assays (MDAs) have been developed to help overcome these problems by simultaneously measuring antibodies against a large panel of influenza hemagglutinin (HA) proteins with a minimal amount of sample in a high throughput way. MDAs will likely be a powerful tool for accelerating the study of the humoral immune response to influenza vaccination and the development of a universal influenza vaccine.

Significant recent advances in cancer immunotherapeutics include the vaccination of cancer patients with tumor antigen-associated peptide-pulsed dendritic cells (DCs). DC vaccines with homogeneous, mature, and functional activities are required to achieve effective acquired immunity; however, the yield of autologous monocyte-derived DCs varies in each patient. Priming with a low dose of recombinant human granulocyte colony-stimulating factor (rhG-CSF) 16–18 h prior to apheresis resulted in 50% more harvested monocytes, with a significant increase in the ratio of CD11c+CD80+ DCs/apheresed monocytes. The detection of antigen-specific cytotoxic T lymphocytes after Wilms’ tumor 1-pulsed DC vaccination was higher in patients treated with rhG-CSF than those who were not, based on immune monitoring using tetramer analysis. Our study is the first to report that DC vaccines for cancer immunotherapy primed with low-dose rhG-CSF are expected to achieve higher acquired immunogenicity.

Dengue is one of the life-threatening common neglected tropical diseases of the world, yet to develop any therapeutic for its treatment and prevention. Although there is a licensed vaccine reported, but becomes less efficacious due to the presence of multiple serovars of the dengue virus (DENV). Thus, an efficacious dengue vaccine potent to work against all the serovars is very crucial and time-demanding. Here we used a comprehensive hierarchical reverse vaccinology approach to design an epitope-based vaccine, targeted against multiple serovars of the DENV. Conservancy and population coverage analysis of the promiscuous epitopes revealed the robust immune response against multiple serovars of the DENV and various ethnicities. Final vaccine constructs comprising of B and T-cell epitopes, Universal pan-HLA DR or PADRE (AKFVAAWTLKAAA) sequence, and an adjuvant (β-defensin) at N-terminal of the construct with suitable linkers. Physiochemical properties and secondary structure profiling of the vaccine protein secured its hydrophilic, thermostable, and other structural nature. Molecular docking analysis indicates the deep binding of the proposed vaccine in the binding groove of the human immune TLR4 receptor present on the dendritic cell. In addition, disulfide engineering was coped to extend its stability. Furthermore, molecular dynamics simulation of the modeled vaccine-TLR8 complex showed minimum deformability. Finally, in silico cloning approach of the vaccine construct within an expression vector (pET28a+) assure good expression. Proposed vaccine may give novel insights for treatment of dengue patients.

Marburg virus disease (MVD) is a hemorrhagic fever and cause death up to 88% of people and is the same as Ebola virus, It is transmitted through skin contact or mucous membrane in the eyes, nose or mouth with blood or body fluids like urine, saliva sweat, feces and by object contaminated with body fluids. Despite these facts, yet there is no approved vaccine have been developed for the eradication of Marburg virus infections. Therefore, this study described a multi epitope-based peptide vaccine against Marburg virus viral protein 35, using several immunoinformatics tools combined with molecular docking studies. Utilizing Vaxijen 2.0 server, the V35 protein revealed to be antigenic with a score of 0.4316. Prediction of the T-cell and B-cell epitopes was then conducted. RTFDAFLGV epitope was found to be the most promising one with binding affinity to the highest numbers of MHC I alleles, a positive score in the Class I immunogenicity study and non-allergen. These results were further confirmed by the good interaction of RTFDAFLGV to the groove of HLA-A*02:01 with binding energy of -8.1 kcal/mole. Finally, the vaccine was cloned in silico to ensure its validity and efficiency of expression. To ensure its safety and immunogenic profile, in-vitro and in-vivo bioassays are recommended to confirm these findings.

We aimed to assess awareness, knowledge, and attitudes of healthy pregnant women towards human papillomavirus (HPV), to estimate factors associated with a positive attitude towards HPV immunization and to assess the uptake of the vaccine among their children. A cross-sectional study was conducted at the University Clinic of Gynecology and Obstetrics, Belgrade, Serbia among pregnant women attending their regular gynecological check-ups at the 12th gestational week. Knowledge about HPV and HPV vaccine was assessed using a specifically designed 12-item and 5-item questionnaires. Out of total 265 included women, 79.3% had heard of HPV, and 37.5% knew that HPV vaccine exists. HPV vaccine knowledge score was associated with higher odds for a positive attitude towards vaccination of both female (OR = 4.10, 95% CI 1.50-11.29) and male (OR = 3.71, 95% CI 1.52-9.01) child. The number of children (OR = 1.32, 95% CI 1.04-1.67) and high vaccine knowledge score (OR = 1.64 95% CI 1.13-2.39) were independent predictors associated with willingness to vaccinate child against HPV. The gynecologist was the preferable point of reference for information seeking about the HPV vaccine. Despite relatively high HPV awareness and knowledge among pregnant women in Serbia, about one-third of them are HPV vaccine aware, and are willing to vaccinate their children against HPV.

We aimed to evaluate the safety of maternal Tdap we assessed health events by examining the difference in birth and hospital-related outcomes of infants with and without fetal exposure to Tdap. This was a retrospective cohort study using linked administrative datasets. The study population were all live-born infants in New Zealand (NZ) weighing at least 400 grams at delivery and born to women who were eligible for the government funded, national-level vaccination program in 2013. Infants were followed from birth up to one year of age. There were a total of 69,389 eligible infants in the cohort. Of these, 8,299 infants were born to 8,178 mothers exposed to Tdap (12%), primarily between 28-38 weeks gestation as per the national schedule. Among the outcomes, we found a reduced risk for moderate to late preterm birth, low birth weight, small for gestational age, large for gestational age, respiratory distress syndrome, transient tachypnea of newborn, tachycardia or bradycardia, haemolytic diseases, other neonatal jaundice, anaemia, syndrome of infant of mother with gestational diabetes, and hypoglycemia in infants born to vaccinated mothers. There was no association between maternal Tdap and stillbirth, infant Apgar score at 5 minutes after birth, microcephaly, asphyxia, sepsis or infection, or hypoxic ischemic encephalopathy. Infant exposure to Tdap during pregnancy was associated with a higher mean birthweight (not clinically significant) and higher odds for ankyloglossia and neonatal erythema toxicum diagnoses. There were insufficient observations to allow examination of the effect of Tdap on extreme preterm and very preterm birth, and infant death. Overall, we found no outcomes of concern associated with the administration of Tdap during pregnancy.

The worldwide outbreak of a novel coronavirus, SARS-CoV-2 has caused a pandemic of respiratory disease. Due to this emergency, researchers around the globe have been investigating the evolution of the genome of SARS-CoV-2 in order to design vaccines. Here I examined the evolution of GC content of SARS-CoV-2 by comparing the genomes of the members of the group Betacoronavirus. The results of this investigation revealed a highly significant positive correlation between the GC contents of betacoronaviruses and their divergence from SARS-CoV-2. The betacoronaviruses that are distantly related to SARS-CoV-2 have much higher GC contents than the latter. Conversely, the closely related ones have low GC contents, which are only slightly higher than that of SARS-CoV-2. This suggests a systematic reduction in the GC content in the SARS-CoV-2 lineage over time. The declining trend in this lineage predicts a much-reduced GC content in the coronaviruses that will descend/evolve from SARS-CoV-2 in the future. Due to the three consecutive outbreaks (MERS-CoV, SARS-CoV and SARS-CoV-2) caused by the members of the SARS-CoV-2, the scientific community is emphasizing the need for universal vaccines that are effective across many strains including those, that will inevitably emerge in the near future. The reduction in GC contents implies an increase in the rate of GC→AT mutations than that the mutational changes in the reverse direction. Therefore, understanding the evolution of base composition and mutational patterns of SARS-CoV-2 could be useful in designing broad-spectrum vaccines that could identify and neutralize the present and future strains of this virus.

Vaccination against Newcastle disease (ND), a devastating viral disease of chicken, is often hampered by thermal inactivation of the live vaccines, in particular in tropical and hot climate conditions. In the past “thermostable” vaccine strains (I-2) have been proposed to overcome this problem. In the current study, we compared the thermal stability of 6 commercially available ND vaccines. Subjected to 37°C as lyophilized preparation, two vaccines containing I-2 strains were more sensitive to inactivation than a third I-2 vaccine or when compared to three other vaccines based on different strains. However, after reconstitution strains proved to have a comparable tenacity. Interestingly, all vaccines retained a sufficient virus dose for protection (106 EID50) after 1 day at 37°C, still. However, experiments exposing ND-vaccines to elevated temperatures of 51°C and 61°C, clearly demonstrated inactivation of all dissolved vaccines within 2 to 4 hours. The data indicate preparation that specific factors may influence thermal stability rather than strain specific characteristics. Regardless of the ND strain used, the appropriate cold chain is mandatory for live ND-vaccines.

Influenza B virus (IBV) is considered a major respiratory pathogen responsible for seasonal respiratory disease in humans, particularly severe in children and the elderly. Seasonal influenza vaccination is considered the most efficient strategy to prevent and control IBV infections. Live attenuated influenza virus vaccines (LAIVs) are thought to induce both humoral and cellular immune responses by mimicking a natural infection, but their effectiveness have recently come into question. Thus, the opportunity exists to find alternative approaches to improve overall influenza vaccine effectiveness. Two alternative IBV backbones were developed with re-arranged genomes, re-arranged M (FluB-RAM) and a re-arranged NS (FluB-RANS). Both re-arranged viruses showed temperature sensitivity in vitro compared to the WT type B/Bris strain, were genetically stable over multiple passages in embryonated chicken eggs and were attenuated in vivo in mice. In a prime-boost regime in naïve mice, both re-arranged viruses induced antibodies against HA with hemagglutination inhibition titers considered of protective value. In addition, antibodies against NA and NP were readily detected with potential protective value. Upon lethal IBV challenge, mice previously vaccinated with either FluB-RAM or FluB-RANS were completely protected against clinical disease and mortality. In conclusion, genome re-arrangement renders efficacious LAIV candidates to protect mice against IBV.

High throughput multiplex serological systems enable the small developer to set up tests at small cost, for microbes for which there are no commercial tests, and for aspects which have not been addressed by them. An example is testing for Zika and Tick Borne Encephalitis virus antibodies, where antigenic cross-reactions make diagnosis problematic. Our technique variant, Suspension Multiplex Immunoassay (SMIA) allows many samples to be tested for antibodies to many antigens in a short time. Computational compensation for cross-reactions is possible if a SMIA panel contains most of the potentially cross-reacting antigens. Using antibody avidity and pattern of reactivity to whole virus and nonstructural protein, antibodies due to vaccination and infection, respectively, as well as probable degree of protection, can be determined with high throughput. These multiplex techniques hold great promise for future diagnostic development. Theoretically, even large scale serological monitoring, like blood donor pathogen testing, could be done inexpensively and rationally with multiplex serology developed in house. However, the quality control demands are steep and in most cases out of scope for a single laboratory. There remain however a number of clinical applications where in house multiplex serology can be performed with adequate quality control under high throughput conditions.

Artificially designed, chimeric peptide-based recombinant vaccines are novel approaches to combat the phylogenetically diverse Foot and Mouth Disease (FMD) Virus (FMDV) strains. Among seven distinct serotypes, only serotype O and A are dominantly circulating in Bangladesh and neighbouring countries of Asia, where transboundary transmission, recurrent outbreaks and emergence of novel lineages FMDV are highly prevalent. The objective of this study was to develop multi-epitope recombinant peptides, procuring immunogenicity against circulating diverse subtypes of FMDV serotype O and A. Two chimeric peptides, named B1 (41.0 kDa) and B3 (39.3 kDa), have been designed to incorporate potential B-cell and T-cell epitopes selected from multiple FMDV strains, including previously reported and newly emerged sub-lineages. After expression, characterization and immunization of guineapigs with considerable antigen load of B1 and B3 followed by the serological assays revealed the significant protective immunogenicity, developed from the higher (100 µg) doses of both antigens, against most of the currently prevalent serotype O and A strains of FMDV. The efficient expression, antigenic stability, and multivalent immunogenic potency of the chimeric peptides strongly indicate their credibility as novel vaccine candidates for FMDV serotypes O and A circulating in Bangladesh and surrounding territories.

The RV144 trial represents the only vaccine trial to demonstrate any protective effect against HIV-1 infection. While the reason(s) for this protection are still being evaluated, it serves as justification for widespread efforts aimed at developing new, more effective HIV-1 vaccines. Advances in our knowledge of HIV-1 immunogens and host antibody responses to these immunogens are crucial to informing vaccine design. While the envelope (Env) protein is the only viral protein present on the surface of virions, it exists in a complex trimeric conformation and is decorated with an array of variable N-linked glycans, making it an important but difficult target for vaccine design. Thus far, efforts to elicit a protective humoral immune response using structural mimics of native Env trimers have been unsuccessful. Notably, the aforementioned N-linked glycans serve as a component of many of the epitopes crucial for the induction of potentially protective broadly neutralizing antibodies (bnAbs). Thus, a greater understanding of Env structural determinants, most critically Env glycosylation, will no doubt be of importance in generating effective immunogens. Recent studies have identified the HIV-1 Env signal peptide (SP) as an important contributor to Env glycosylation. Further investigation into the mechanisms by which the SP directs glycosylation will be important, both in the context of understanding HIV-1 biology and in order to inform HIV-1 vaccine design.

Aleutian mink disease virus (AMDV) is known to cause the most significant disease in the mink industry. It is globally widespread and manifested as a deadly plasmacytosis and hyperglobulinemia. So far, measures to control viral spread have been limited to manual serological testing for AMDV-positive mink. Further, due to the persistent nature of this virus, attempts to eradicate Aleutian disease (AD) have largely failed. Therefore, effective strategies to control viral spread are of crucial importance for wildlife protection. One potentially key tool in the fight against this disease is by immunization of mink against AMDV. Throughout many years, several researchers have tried to develop AMDV vaccines and demonstrated varying degrees of protection in mink by those vaccines. Despite these attempts, there are currently no vaccines available against AMDV, allowing the continuation of the spread of Aleutian disease. Herein, we summarize previous AMDV immunization attempts in mink as well as other preventative measures with the purpose to shed light on future studies designing such a potentially crucial preventative tool against Aleutian disease.

Objective: This study aimed to evaluate the antibody responses in two adult age groups after diphtheria vaccination. Study Design: An observational analytic study was carried out to determine the difference in serum titer of anti-diphtheria antibody. Methods: Serum antibody titers were measured just before and 3 months after injection of Diphtheria toxoid vaccine. Vaccine was given to two adult age groups of health care personnel in hospital: the young (< 40 years) and the middle-aged (≥ 40 years). Data were analyzed using the Mann-Whitney test (p < 0.05). Results: Significant increase in serum anti-diphtheria antibody titers were recorded after vaccination in both age group (p < 0.001 in young adult and p = 0.001 in middle-aged adult, respectively). There were no substantial differences between the two groups in terms of antibody titer before vaccination (p = 0.741), 3 months after vaccination (p = 0.317) and in the increase of antibody titer (p = 0.479). Conclusions: This study showed that there was no significant difference in the increase of anti-diphtheria antibody titers between the two age groups, proving that both young and middle-aged adults had an equal immune response to a given diphtheria vaccine.

Staphylococcus aureus mastitis remains a major challenge for dairy farming. Here, 24 mice were immunized and divided into four groups: G1: control; G2: Granulocyte Macrophage Colony-Stimulating Factor (GM-CSF) DNA vaccine; G3: F0F1 ATP synthase subunit α (SAS), succinyl-diaminopimelate (SDD), and cysteinyl-tRNA synthetase (CTS) recombinant proteins; and G4: SAS+SDD+CTS plus GM-CSF DNA vaccine. The lymphocyte subpopulations and the intracellular interleukin-17A (IL-17A) and interferon-γ production in the draining lymph node cells were immunophenotyped by flow cytometry. The immunophenotyping and lymphocyte proliferation was determined in spleen cells cultured with and without S. aureus stimulus. Immunization with S. aureus recombinant proteins generated memory cells in draining lymph nodes. Immunization with the three recombinant proteins plus GM-CSF DNA led to an increase in the percentage of IL-17A+ cells among overall CD44+ (memory), T CD4+, CD4+ T CD44+ CD27-, γδ TCR, γδ TCR+ CD44+ CD27+ and TCRVγ4+ cells. Vaccination with S. aureus recombinant proteins associated with GM-CSF DNA vaccine downregulates TH2 immunity. Immunization with the three recombinant proteins plus the GM-CSF DNA led to a proliferation of overall memory T, CD4+ and CD4+ TEM cells upon S. aureus stimulus. This approach fostered type 3 immunity, suggesting the development of a protective immune response against S. aureus.

This study aimed to evaluate the mixed and homogeneous application of the inactivated SARS-CoV-2 vaccine CoronaVac (CV) and the mRNA vaccine BNT162b2 (BNT). This prospective cohort study included 235 health care workers, who had received two prime shots with CoronaVac. They were divided into three cohorts after the third month: Cohort-I (CV/CV); Cohort-II (CV/CV/CV) and Cohort-III (CV/CV/BNT). Anti-S-RBD-IgG and total an-ti-spike/anti-nucleocapsid-IgG antibody concentrations were examined in vaccinated health workers at the 1st, 3rd and 6th months following the second dose of the vaccination. The mean age of 235 health care workers who participated in the project was 39.51±10.39 (min-max: 22-64). At the end of the 6th month, no antibodies were detected in 16.7% of Cohort-I participants, and anti-S-RDB IgG levels showed a decrease of 60% compared to the levels of the 3rd month. The antibody concentrations of the 6th month were found to have increased by an average of 5.13 times compared to the 3rd-month levels in the Cohort-II and 20.4 times in Cohort-III. The heterologous vaccination strategy “CoronaVac and BNT162b2 regimen” is able to induce a stronger immunity and it will help remove inequalities in the developing world where CoronaVac was the initial prime.

African swine fever (ASF) is a pandemic threat to the global pig industry and wild suids. A safe and efficacious vaccine could monumentally assist in disease eradication. In the past years, promising live attenuated vaccine candidates emerged in proof-of-concept experiments, among them, “ASFV-G-∆MGF”. In our study, we tested the vaccine candidate in three animal experiments intramuscularly in domestic pigs one orally in wild boar. Further, a macrophage-grown vaccine virus and a virus grown on permanent cells could be employed. Irrespective of the production system of vaccine virus, a two-dose intramuscular immunization could induce close to sterile immunity with full clinical protection against challenge infection. After oral immunization, 50% of the vaccinees seroconverted and all responders were completely protected against subsequent challenge. All non-responders developed ASF upon challenge with two acute lethal infections and two mild and transient courses. The latter results show a lower efficiency after oral administration that would have to be taken into consideration when designing vaccination-based control measures. Our findings suggest that “ASFV-G-∆MGF” could help to contain the disease under an appropriate vaccination campaign. Further research is needed to characterize safety aspects and define possible improvements of oral efficiency.

A model to predict the relative levels of respiratory and fecal-oral transmission potentials of coronaviruses (CoVs) by measuring the percentage of protein intrinsic disorder (PID) of the M (Membrane) and N (nucleoprotein) proteins in their outer and inner shells, respectively, was built before the MERS-CoV outbreak. Application of this model to the 2003 SARS-CoV indicated that this virus with M_PID = 8.6% and N_PID = 50.2% falls into group B, which consists of CoVs with intermediate levels of both fecal-oral and respiratory transmission potentials. Further validation of the model came with MERS-CoV (M_PID = 9%, N_PID = 44%) and SARS-CoV-2 (M_PID = 5.5%, N_PID = 48%) falling into the groups C and B, respectively. Group C contains CoVs with higher fecal-oral but lower respiratory transmission potentials. Unlike SARS-CoV, SARS-CoV-2 with M_PID = 5.5% has one of the hardest outer shells among CoVs. This shell hardness is believed to be responsible for high viral loads in the mucus and saliva making it more contagious than SARS-CoV. The hard shell is able to resist the anti-microbial enzymes in body fluids. Further searches have found that high rigidity of outer shell is characteristic for the CoVs of burrowing animals, such as rabbits (M_PID = 5.6%) and pangolins (M_PID = 5-6%), which are in contact with the buried feces. A closer inspection of pangolin-CoVs from 2017-19 reveals that these animals provided a unique window of opportunity for the entry of an attenuated SARS-CoV-2 precursor into the human population in 2017 or earlier, with the subsequent slow and silent spread as a mild cold that followed by its mutations into the current more virulent form. Evidence of this lies in the similarity of shell disorder and genetic proximity of the pangolin-CoVs to SARS-CoV-2 (~90%). A 2017 pangolin-CoV strain shows evidence of higher levels of attenuation and higher fecal-oral transmission associated with lower human infectivity via having lower N_PID (44.8%). Our shell disorder analysis also revealed that lower inner shell disorder is associated with the lesser virulence in a variety of viruses.

Influenza B virus (IBV) is a major respiratory pathogen of humans, particularly in the elderly and children and vaccines are the most effective way to control it. In previous work, incorporation of two mutations (E580G, S660A) along with the addition of a HA epitope tag in the PB1 segment of B/Brisbane/60/2008 (B/Bris) resulted in an attenuated strain that was safe and effective as a live attenuated vaccine. A third attempted mutation (K391E) in PB1 was not always stable. Interestingly, viruses that maintained the K391E mutation were associated with the mutation E48K. To explore the contribution of the E48K mutation for stability of the K391E mutation, a vaccine candidate was generated by inserting both mutations along with attenuating mutations E580G and S660A in PB1 of B/Bris (B/Bris PB1att 4M). Serial passage of the B/Bris PB1att 4M vaccine candidate in eggs and MDCK indicated high stability. In silico structural analysis revealed a potential interaction between amino acids at positions 48 and 391. In mice, B/Bris PB1att 4M was safe and provided complete protection against homologous challenge. These results confirm the compensatory effect of mutation E48K to stabilize the K391E mutation, resulting in a safer, yet still protective, IBV LAIV vaccine.

Mosquitoes conveying Plasmodium store parasites into the skin of the mammalian host. Parasites make a trip through the circulation system to the liver, where they cross a few hepatocytes prior to building up a disease. Inside the last hepatocyte the parasite goes through morphogenesis and afterward abiogenetically partitions to become more than 20,000 blood-infective parasites, called merozoites. On account of P. vivax, P. ovale, and P. cynomolgi, the parasites can stay lethargic in the liver in structures called hypnozoites. The merozoites are delivered once again into the circulation system, where they start the repetitive blood stage. Inside erythrocytes, a little division of parasites separate into male or female gametocytes. These gametocytes are ingested by the mosquito during blood taking care of, where they will duplicate explicitly, in the long run prompting the arrangement of sporozoites

The development of universal influenza vaccines, i.e. vaccines that can provide broad protection against seasonal and potentially pandemic influenza viruses, has been a priority for more than 20 years. Several approaches have been proposed that redirect the adaptive immune responses from immunodominant hypervariable regions to low-immunogenic but highly conserved regions of viral proteins. Here we induced broadly reactive anti-hemagglutinin (HA) stalk antibody by sequential immunizations with live attenuated influenza vaccines (LAIVs) expressing chimeric HA (cHA). These vaccines contained the HA stalk domain from H1N1pdm09 virus but antigenically unrelated globular head domains from avian influenza viruses H5N1, H8N4 and H9N2. In addition, the source of the viral nucleoprotein (NP) of the LAIV strains was changed from A/Leningrad/17 master donor virus (MDV) to wild-type (WT) H1N1pdm09 virus, in order to induce CD8 T-cell immune responses more relevant to current infections. To avoid any difference in protective effect of the various anti-neuraminidase (NA) antibodies, all LAIVs were engineered to contain the NA gene of Len/17 MDV. Naïve ferrets were immunized with three doses of (i) classical LAIVs containing non-chimeric HA and NP from MDV (LAIVs (NP-MDV)); (ii) cHA-based LAIVs containing NP from MDV (cHA LAIVs (NP-MDV)); and (iii) cHA-based LAIVs containing NP from H1N1pdm09 virus (cHA LAIVs (NP-WT)). A high-dose challenge with H1N1pdm09 virus induced significant pathology in the control, non-immunized ferrets, including high virus titers in respiratory tissues, clinical signs of disease and histopathological changes in nasal turbinates and lung tissues. All three vaccination regimens protected animals from clinical manifestations of disease: immunized ferrets did not lose weight or show clinical symptoms, and their fever was significantly lower than in the control group. Further analysis of virological and pathological data revealed the following hierarchy in the cross-protective efficacy of the vaccines: cHA LAIVs (NP-WT) > cHA LAIVs (NP-MDV) > LAIVs (NP-MDV). This ferret study showed that prototype universal LAIVs that combine the two approaches of inducing anti-HA stalk antibody and more relevant CD8 T-cell immune responses are highly promising candidates for further clinical development.

Porcine Circovirus 2 (PCV2) vaccines are based on either inactivated whole virion, or recombinant ORF2 capsid protein assembled into Virus-like Particles (VLPs). No data are available instead about the immunizing properties of free, non-assembled capsid protein. To investigate this issue, ORF2 of a reference PCV2b strain was expressed in a Baculovirus-based expression system without assembly into VLPs. The free purified protein was formulated into an oil vaccine at three distinct Ag payloads: 10.8 / 3.6 / 1.2 micrograms /dose. Each dose was injected intramuscularly into five, 37-day old piglets, carefully matched for maternally-derived antibody. Five control piglets were injected with sterile PBS in oil adjuvant. Twenty-eight days later, all the pigs were challenged intranasally with 200,000 TCID50 of PCV2b strain DV6503. After challenge infection, all the pigs remained in good clinical conditions. The recombinant vaccine did not induce significant antibody and PCV2-specific IFN-gamma responses. ELISPOT and lymphocyte proliferation data confirmed poor induction of cell-mediated immunity. In terms of PCV2 viremia, there was no significant difference between vaccinated and control animals. The histological data indicated the absence of a detectable viral load and of PCVAD lesions in both vaccinated and control animals, as well as of histiocytes and multi-nucleated giant cells. We conclude that free, non-assembled ORF2 capsid protein does not induce protective immunity.

Sporotrichosis is a subcutaneous mycosis affecting humans and other animals that can be transmitted a zoonosis with cats as the main vector. The conventional anti-fungal therapy is especially inefficient in immunocompromised patients, who tend to develop the most severe forms of the disease, thus prompting the search for alternative therapies. Given their antigen-presenting properties, dendritic cells (DCs) have been used in both prophylactic and therapeutic vaccination strategies. Hence, this study aims to assess the use of DCs as a prophylactic tool in sporotrichosis by evaluating the immune profile induced by Sporothrix schenckii cell wall proteins (SsCWP)-stimulated bone-marrow-derived DCs (BMDCs). Mouse BMDCs were stimulated with SsCWP for 24 hours and analyzed for the surface expression of co-stimulatory molecules and TLR-4, as well as the secretion of proinflammatory cytokines and IL-10. Following that, activated BMDCs were cocultured with splenocytes for 72 hours and had the same cytokines measured in the supernatant. SsCWP-stimulated BMDCs showed higher expression of CD80, CD86, and CD40, but not TLR-4, and higher secretion of IL-6, IL-17A, and TNF. On the other hand, higher levels of IFN-γ, IL-10, and IL-2 were found in the supernatants of the coculture as compared with the BMDCs alone; TNF secretion was almost completely abrogated, whereas IL-6 was only partially inhibited and IL-17A was unaffected. Our results thus suggest SsCWP-stimulated BMDCs are able to induce a Th1-prone cytokine profile, known to be protective against other fungal diseases. This result could lead to evaluate the development of prophylactic and/or therapeutic DC-based tools against sporotrichosis.

Mosquito-borne viral disease dengue is a global public health problem causing a wide spectrum of clinical manifestations ranging from mild dengue fever to severe dengue with plasma leakage and bleeding which are often associated to fatality. To date, there are no specific medications to treat dengue and prevent the risk of hemorrhage. Dengue is caused by one of the four related antigenically distinct serotypes, DENV-1 to DENV-4. The growing burden that represents the four DENV serotypes has intensified both basic and applied researches to better understand the dengue physiopathology. It has been proposed a significant role for the secreted soluble DENV nonstructural protein 1 (sNS1) glycoprotein in the pathogenesis of severe dengue. Here, we provided an overview on current knowledge about the role of sNS1 in the immunopathogenesis of dengue disease. The reasons for the consideration of sNS1 in the design of future dengue vaccine candidates will be discussed.

In the present day and age, cancer is still a life-limiting factor whose one of the therapeutic strategies is immunotherapy with vaccines. This research aims to prepare and characterize nanoliposomal vaccine formulation attached to HER2/neu-derived peptide (AE36) with or without CpG-ODN, and to evaluate its immunological responses to the therapy using BALB/c mice with HER2 overexpressing breast cancer. Methods: AE36 was conjugated to the liposomes containing DOTAP, DOPE and Cholesterol. Such formulations are able to produce CD8+ and CD4+ responses and induce synthesis of cytokines detectable via Enzyme-linked immunosorbent assay kits, cytotoxicity testing and intracellular cytokine staining combined with flow cytometry. Therapeutic and prophylactic effectiveness were evaluated through the formulation in samples. The highest effectiveness was found in DDC-peptide + CpG-ODN in both prophylactic and therapeutic studies, which decreased the size of tumors significantly and increased time of survival. These nanoliposomes linked to AE36 could be regarded as an appropriate candidate for the treatment and also for prophylaxis of HER2+ breast cancer; however further studies are needed.

Although vaccinating the world is adopted by the WHO to limit COVID-19 transmission, people’s worries about vaccines may suppress their desire for vaccination despite vaccine availability. This study aimed to evaluate the levels of stress and anxiety among 250 Jordanians who received their first vaccine dose at a local community health center. The respondents completed the stress and anxiety subscales of the Depression Anxiety and Stress scale 21 (DASS-21) pre- and post-vaccination. The respondents expressed more moderate-severe levels of stress pre than post vaccination (20.8% and 13.2%, respectively). Meanwhile, 37.2% and 45.2% of the respondents expressed moderate-severe anxiety pre and post vaccination, respectively. Wilcoxon signed-rank test revealed that the drop in the level of stress from pre (median (IQR) = 5 (1-8)) to post vaccination (median (IQR) = 3 (1-7)) was statistically significant (z = -3.81, p = 0.001, r = 0.17) while the increase in anxiety was not. Anxiety median significantly dropped among individuals experiencing mild to severe anxiety pre vaccination. Similarly, stress and anxiety significantly increased among individuals expressing normal anxiety pre vaccination (z = -3.57 and -8.24, p values = 0.001, r = 0.16 and 0.37, respectively). Age positively correlated with post vaccination anxiety among respondents with mild pre vaccination anxiety, and it negatively correlated with pre vaccination level of stress in the normal anxiety group. Gender, marital status, respondents’ level of education, and history of COVID-19 infection had no significant correlation with anxiety or stress at either point of measurement. Overcoming their hesitancy to receive COVID-19 vaccine, individuals with normal levels of anxiety experienced a rise in their distress symptoms following immunization. On the contrary, vaccination seemed to desensitize anxious individuals. Policymakers need to formulate a population-specific plan to increase vaccine preparedness and promote psychological well-being over all during the pandemic.

Little is known about the long-term durability of the induced immune response in subjects af-fected by obesity, particularly in those with an abdominal distribution of adipose tissue. We evaluated SARS-CoV-2-specific antibody response after BNT162b2 vaccine booster dose, com-paring individuals with abdominal obesity (AO) with those without, discerning between indi-viduals previously infected or not. IgG-TrimericS were measured in 511 subjects at baseline, 21 days after vaccine dose-1 and at one, three, six and nine months after dose-2 and at one and three months after booster dose. Nucleocapsid antibodies were assessed at baseline and at the end of the study to detect SARS-CoV-2 infection. To evaluate the three-months difference in absolute variation of IgG-TrmicericS levels from booster dose we used multivariable linear regression that showed interaction between AO and SARS-CoV-2 infection status (p=0.016). AO is associated with higher absolute IgG-TrimericS variation in prior infected individuals, regardless of possi-ble confounders and IgG-TrimericS levels at booster dose (p=0.0125). No interaction was evinced using BMI in the same regression model (p=0.418). The robust response in the development of antibodies after booster dose, observed in people with OA and previous infection, may support the recommendations to undergo the booster dose also in this population group.

We reviewed the association between seasonal influenza vaccination and the risk of SARS-CoV-2 infection or complicated illness or poor outcome (e.g. severe disease, need for hospitalization or ventilatory support, or death) among COVID-19 patients. None of the studies that were reviewed (n=12) found a significant increase in the risk of infection or in the illness severity or lethality, while some reported significantly inverse associations. Our findings support measures aimed at raising influenza vaccination coverage in the coming months.

Middle East Respiratory Syndrome coronavirus (MERS-CoV) infects dromedary camels and zoonotically infects humans, causing a respiratory disease with severe pneumonia and death. With no approved antiviral or vaccine interventions for MERS, vaccines are being developed for camels to prevent virus transmission into humans. We have previously developed a chimpanzee adenoviral vector-based vaccine for MERS-CoV (ChAdOx1 MERS) and reported its strong humoral immunogenicity in dromedary camels. Here, we looked back at total RNA isolated from three immunised dromedaries pre and post-vaccination during the first day; and performed RNA sequencing and bioinformatic analysis in order to shed light on the molecular immune responses following a ChAdOx1 MERS vaccination. Our finding shows that a number of transcripts were differentially regulated as an effect of the vaccination, including genes that are involved in innate and adaptive immunity, such as type I and II interferon responses. The camel Bcl-3 and Bcl-6 transcripts were significantly upregulated, indicating a strong activation of Tfh cells, B cell, and NF-kB pathways. In conclusion, this study gives an overall view of the first changes in the immune transcriptome of dromedaries after vaccination; it supports the potency of ChAdOx1 MERS as a potential camel vaccine to block transmission and prevent new human cases and outbreaks.

Chronic HCV infection and associated liver cancer impose a heavy burden on the healthcare system. Direct acting antivirals eliminate HCV, unless it is drug resistant, and partially reverse liver disease, but they cannot cure HCV-related cancer. Possible remedy could be a multi-component immunotherapeutic vaccine targeting both HCV-infected and malignant cells, also those not infected with HCV. To meet this need we developed a two-component DNA vaccine based on the highly conserved core protein of HCV to target HCV-infected cells, and a renowned tumor associated antigen telomerase reverse transcriptase (TERT) based on the rat TERT, to target malignant cells. Their synthetic genes were expression-optimized, and HCV core was truncated after aa 152 (Core152opt) to delete the domain interfering with immunogenicity. Core152opt and TERT DNA were highly immunogenic in BALB/c mice, inducing IFN-γ/IL-2/TNF-α response of CD4+ and CD8+ T cells. Also, DNA-immunization with TERT enhanced cellular immune response against luciferase encoded by a co-delivered plasmid (Luc DNA). However, DNA-immunization with Core152opt and TERT mix resulted in abrogation of immune response against both components. A loss of bioluminescent signal after co-delivery of TERT and Luc DNA into mice indicated that TERT affects the in vivo expression of luciferase directed by the immediate early cytomegalovirus and interferon-β promoters. Panel of mutant TERT variants was created and tested for their expression effects. TERT with deleted N-terminal nucleoli localization signal and mutations abrogating telomerase activity still suppressed the IFN-β driven Luc expression, while the inactivated reverse transcriptase domain of TERT and its analogue, enzymatically active HIV-1 reverse transcriptase, exerted only weak suppressive effects, implying that suppression relied on the presence of the full-length/nearly full-length TERT, but not its enzymatic activity. The effect(s) could be due to interference of the ectopically expressed xenogeneic rat TERT with biogenesis of mRNA, ribosomes and protein translation in murine cells, affecting the expression of immunogens. HCV core can aggravate this effect, leading to early apoptosis of co-expressing cells, preventing the induction of immune response.

The COVID-19 pandemic has highlighted the adverse consequences created by an infodemic specifically on compliance with public health guidance and vaccine uptake. COVID-19 vaccine hesitancy is a complex construct that is related to health beliefs, misinformation exposure, and perceptions of governmental institutions. This study draws on theoretical models and current data on the COVID-19 infodemic to explore the association between perceived risk of COVID-19, levels of misinformation endorsement, and opinions about the government response on vaccine uptake. We surveyed a sample of 2,697 respondents from the US, Canada, and Italy using a mobile platform between 21-28 May, 2021. Using multivariate regression, we found that country of residence, risk perception of contracting and spreading COVID-19, perception of government response and transparency, and misinformation endorsement was associated with the odds of vaccine hesitancy. Higher perceived risk was associated with lower odds of hesitancy, while lower perceptions of government response, and higher misinformation endorsement were associated with higher hesitancy.

On 17 June 2022, the U.S. FDA authorized the Pfizer-BioNTech and Moderna COVID-19 (SARS-CoV-2) vaccines for emergency use in children ages 6 months – 4 years. Seroprevalence has increased during the current Omicron variant wave for children under 5 years and the burden of hospitalization for this age group is similar or exceeds other pediatric vaccine preventable diseases. Research following the October 2021 approval of vaccines for children 5 – 11 indicates high prevalence of parental vaccine hesitancy and low uptake, underscoring the urgency of understanding attitudes and beliefs driving parental COVID-19 vaccine rejection and acceptance for younger children. One month prior to FDA approval, in the present study 411 U.S. female guardians of children 1 – 4 years from diverse racial/ethnic, economic, and geographic backgrounds participated in a mixed method online survey assessing determinants of COVID-19 pediatric vaccine hesitancy. Only 31.3% of parents intended to vaccinate their child, 22.6% were unsure, and 46.2% intended not to vaccinate. Logistic regression indicated significant barriers to vaccination uptake including: Concerns about immediate and long-term vaccination side effects for young children, the rushed nature of FDA approval and distrust in government and pharmaceutical companies, lack of community and family support for pediatric vaccination, conflicting media messaging, and lower socioeconomic status. Vaccine-resistant and unsure parents were also more likely to believe children were not susceptible to infection and that the vaccine no longer worked against new variants. Findings underscore the need for improved public health messaging and transparency regarding vaccine development and approval, the importance of community outreach, and increased pediatrician attention to parental concerns to better improve COVID vaccine uptake for young children.

In addition to the risk of vaccine failure caused by strain mismatch, the production of inactivated FMD vaccines is dangerous if adequate biosafety cannot be maintained. Using a high-throughput sequencing protocol optimized for short nucleic acid fragments, the composition of a local inactivated vaccine was analyzed in depth. The serotype O strain identified in the vaccine was genetically identical to viruses found in recent FMD outbreaks in Egypt.

Efficient textual data distributions (TDD) alignment and generation are open research problems in textual analytics and NLP. It is presently difficult to parsimoniously and methodologically confirm that two or more natural language datasets belong to similar distributions, and to identify the extent to which textual data possess alignment. This study focuses on addressing a segment of the broader problem described above by applying multiple supervised and unsupervised machine learning (ML) methods to explore the behavior of TDD by (i) topical alignment, and (ii) by sentiment alignment. Furthermore we use multiple text generation methods including fine-tuned GPT-2, to generate text by topic and by sentiment. Finally we develop a unique process driven variation of Kullback-Leibler divergence (KLD) application to TDD, named KL Textual Distributions Contrasts (KL-TDC) to identify the alignment of machine generated textual corpora with naturally occurring textual corpora. This study thus identifies a unique approach for generating and validating TDD by topic and sentiment, which can be used to help address sparse data problems and other research, practice and classroom situations in need of artificially generated topic or sentiment aligned textual data.

Background: Renewed measles outbreaks in recent years indicate that despite the routine availability of vaccines for a disease that is considered contagious, dangerous and deadly, many anti-vaccinationists do not vaccinate their children, which consequently endangers public health. This study aimed to investigate the factors that influence mothers to vaccinate their children, and whether the Health Belief Model (HBM) could predict compliance or non-compliance. Methods: This was a quantitative correlational research, utilizing a 40-item questionnaire administered to 181 mothers in Israel. Results: The findings indicated two main factors that affected mothers' intention to vaccinate their children against measles: first, their perception of the vaccine's advantages, and second, their perception of the severity of the disease. It was also found that the HBM variables significantly affected the intention to administer vaccines. Conclusion: Consequently, raising public awareness of the vaccine's advantages and importance to preventing mass infection, as well as attempts by the health system and practitioners to understand the motivations of anti-vaccinationists (including health beliefs and cultural sensitivities) could significantly increase the percentage of vaccinated children, and eradicate the measles epidemic.

All vaccines exhibit specific and nonspecific effects. Specific effects are shown by the efficacy against the target pathogen, while nonspecific effects can be detected by the change in all-cause mortality. The real-world non-COVID-19 all-cause mortality (NCACM) data for the population of England between January 2021 and May 2023 was assessed. All vaccines administered were based on the original Wuhan antigen. Each gender and age group, along with COVID-19 variant shows its own unique NCACM vaccination benefit/disbenefit time profile. The efficacy of COVID-19 vaccination against COVID-19 disease/death per se is undisputed, however, the nonspecific outcomes of COVID–19 vaccination is far more nuanced than have been widely appreciated. This confirms an earlier study on the unanticipated nonspecific effects of influenza vaccination against all-cause winter mortality. Interestingly, a high proportion of NCACM beneficial effects occurred during the first 21 days following COVID-19 vaccination, while the worst example of increased NCACM occurred during the fourth dose of COVID-19 vaccination in 19–40-year-olds for the interval &gt;21 days post vaccination which led to NCACM 3- to 10-times higher than in the unvaccinated. By the time of the Omicron variant, NCACM outcomes in those aged 90+ are mostly adverse. The beneficial nonspecific effects of COVID-19 vaccination increase with age and reach their maximum effect during the second week post vaccination for age groups below 50 years, rising to during the third week for those aged 70+. Finally, we discuss the mechanisms by which COVID-19 vaccination could induce wider nonspecific effects. Most of these mechanisms seem to depend on gene regulation by noncoding RNAs which also interact with mRNAs. We suggest that further international studies are required to discern the nonspecific NCACM effects of the different COVID-19 variants other than the three variants prevalent in the UK, and different types/manufacturer of COVID-19 vaccines which have been employed around the world. We can only speculate regarding the nonspecific effects of the COVID-19 vaccines administered to persons with an asymptomatic infection, and during vaccine waning. Vaccines not only need to be effective against the target pathogen, as primarily determined by antibody production, but need to minimize any unanticipated adverse nonspecific effects against all-cause mortality.

Background: This study describes the attitudes and practices of Brazilian adults regarding the mandatory vaccination for COVID-19 and the hesitancy to children´s vaccination. Methods: The participants answered an online questionnaire disseminated on social networks. An adaptation of the SAGE-WG questionnaire was used to measure the children's vaccination hesitancy. Results: Among 1,007 participants, 677 (67.4%) believed that vaccination for COVID-19 among adults should be mandatory. Just over half of the participants (51.5%) believe that parents and guardians should be free to decide whether their children should be vaccinated against COVID-19, and 9.1% were unsure about this. Younger, non-religious people who have higher self-perceptions of risk for COVID-19, and who evaluate the federal government's performance in combating the disease as bad or very bad, have a higher agreement with mandatory vaccination, a lower agreement that parents and guardians should be free to vaccinate their children, and lower child vaccination hesitancy scores. Conclusion: In Brazil, mandatory COVID-19 vaccination for adults is far from a consensus, and an expressive part of the population believes that parents and guardians should be free to choose whether or not to vaccinate their children. These perceptions and vaccine hesitancy for children are associated with religious and political inclinations.

Dengue is a viral mosquito-borne disease that rapidly spreads in tropical and subtropical countries, including the Philippines. One of its most distinguishing characteristics is the ability of the Dengue Virus (DENV) to easily surpass the innate responses of the body, thus activating B cells of the adaptive immunity to produce virus-specific antibodies. Moreover, Dengvaxia® is the only licensed vaccine for DENV, but recent studies showed that seronegative individuals become prone to increased disease severity and hospitalization. Owing to this limitation of the dengue vaccine, this study determined and compared consensus and unique B cell epitopes among each DENV (1-4) Philippine isolate to identify potential areas of interest for future vaccine studies and therapeutic developments. An in silico-based epitope prediction of forty (40) DENV 1-4 strains, each serotype represented by ten (10) sequences from The National Center for Biotechnology Information (NCBI), was conducted using Kolaskar and Tongaonkar antigenicity, Emini surface accessibility, and Parker hydrophilicity prediction in Immune Epitope Database (IEDB). Results showed that five (5) epitopes were consensus for DENV-1 with no detected unique epitope, one (1) consensus epitope for DENV-2 with two (2) unique epitopes, one (1) consensus epitope for DENV-3 plus two (2) unique epitopes, and two (2) consensus epitopes and one (1) unique epitope for DENV-4. The findings of this study would contribute to determining potential vaccine and diagnostic marker candidates for further research studies and immunological applications against DENV (1-4) Philippine isolates.

Knowing the “point of view” of the immune system is essential to understand the characteristic of a pandemic, such as that generated by the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2, responsible for the Coronavirus Disease (COVID)-19. In this review, we will discuss the general host/pathogen interactions dictating protective immune response or immunopathology, addressing the role of immunity or immunopathology in influencing the clinical infection outcome, and debate the potential immunoprophylactic and immunotherapy strategies required to fight the virus infection.

Influenza virus imprinting is now understood to significantly the influence immune responses and clinical outcome of influenza virus infections that occur later in life. Due to the yearly cycling of influenza viruses, humans are imprinted with the circulating virus of their birth year to subsequently build a complex influenza virus immune history but very little is known about how the imprinting strain influences vaccine responses. To investigate the imprinted host immune responses to split-virion vaccination, we imprinted ferrets with a sublethal dose of the historical seasonal H1N1 strain A/USSR/90/1977. After a +60 day recovery period was given to build immune memory, ferrets were immunized and the challenge at Day 123. Samples were collected throughout the time course and immunological assays were performed to investigate recall mechanisms. The preimmune-vaccinated ferrets did not experience significant disease during challenge while naïve-vaccinated ferrets had severe disease. Hemagglutination inhibition assays showed preimmune ferrets had a more robust antibody response post vaccination, increased virus neutralization activity. Virus specific immunoglobulins were of predominantly the IgG isotype suggesting B cell maturity and plasticity at vaccination. These results are important and should be considered for vaccine design.

The incidence and mortality rates of cervical cancer are rising among young women in Japan. In November 2021, the Japanese Ministry of Health, Labour and Welfare reinstated the active recommendation for the human papillomavirus (HPV) vaccine, which was discontinued in June 2013 due to reports of adverse reactions, including chronic pain and motor dysfunction, following vaccination. However, vaccine hesitancy among the younger generation remains, and it is essential to identify the barriers in vaccination uptake. Therefore, we aim to conduct a randomized study using different methods of providing educational contents to improve health literacy regarding cervical cancer and HPV vaccination among female students in Japan. Here, we present the results of our preliminary report and discuss current topics related to HPV vaccination in Japan. Data were collected from 27 female students—divided into three groups: no intervention, print-based intervention, and SNS-based intervention—using the Health Literacy Scale and Communicative and Critical Health Literacy scale. Our primary results indicate that participants’ knowledge and health literacy improved post intervention. Therefore, medical professionals must provide accurate scientific knowledge regarding routine HPV vaccination and the risk of cervical cancer to young women to improve their health literacy and subsequently increase the HPV vaccination rates.

Rift Valley Fever virus (RVFV) is a zoonotic arbovirus of the Phenuiviridae family. Infection causes abortions in pregnant animals, high mortality in neonate animals and mild to severe symptoms in both people and animals. There is currently an ongoing effort to produce safe and efficacious veterinary vaccines against RVFV in livestock to protect against both primary infection in animals and zoonotic infections in people. To test the efficacy of these vaccines it is essential to have a reliable challenge model in relevant target species, including ruminants. We evaluated two goats breeds (Nubian and LaMancha), three routes of inoculation (intranasal, mosquito-primed subcutaneous and subcutaneous) using an infectious dose of 10⁷ pfu/ml, a virus strain from the 2006-07 Kenyan/Sudan outbreak and compared the effect of using virus stocks produced in either mammalian or mosquito cells. Our results demonstrated that Nubian goats achieved the highest levels and longer duration of viremia. In the Nubian goats, all three routes of inoculation were equally efficient at producing clinical signs, consistent viremia (peak viremia: 1.2x10³ - 1.0x10⁵ pfu/ml serum), nasal and oral shedding of viral RNA (1.5x10¹ – 8x10⁶ genome copies/swab), a systemic infection of tissues, and robust antibody responses. The Nubian goat breed and a needle-free intranasal inoculation technique could both be utilized in future vaccine and challenge studies.

Vaccination is one of the best approaches to control and eradicate foot-and-mouth disease (FMD). To achieve this goal, vaccines with inactivated FMD virus antigen in suitable adjuvants are being used in addition with other control measures. However, only a limited number of vaccine strains are commercially available which often have a restricted spectrum of activity against the different FMD virus strains in circulation. As a result, when new strains emerge, it is important to measure the efficacy of the current vaccine strains against these new variants. This is important for countries where FMD is endemic but also for countries that hold an FMD vaccine bank to be prepared for emergency vaccination. The emergence and spread of the O/ME-SA/Ind-2001 lineage of viruses posed a serious threat to countries which had OIE-endorsed FMD control plans and had not reported FMD for many years. In vitro vaccine matching results showed a poor match (r1-value &lt;0.3) to the more widely used vaccine strain O Manisa and less protection in a challenge test. This paper describes the use of O3039 vaccine strain as an alternative either alone or in combination with the O Manisa vaccine strain with virulent challenge by a O/ME-SA/Ind-2001d sub-lineage virus from Algeria (O/ALG/3/2014). The experiment included challenge at 7 days post vaccination (to study protection and emergency use) and 21 days post vaccination (as would be done in standard potency studies). The results indicated that the O3039 vaccine strain alone as well as the combination with O Manisa is effective against this strain of the O/ME-SA/Ind/2001d lineage offering protection from clinical disease even after 7 days post vaccination and with reduction in viraemia and virus excretion.

Background: Relatively little is known and inconclusive about social inequality in human papillomavirus (HPV) vaccination among teenagers in the United States. This study aims to investigate whether there is a social disparity in HPV vaccination among teenagers and if so, whether it can differ by the source of teen vaccination information (parental reports and provider records). 
Methods: We used the data from the 2019 National Immunization Survey-Teen (NIS-Teen; 42,668 teenagers, aged 13-17) including parental reported vaccination status. Among them, 18,877 teenagers had adequate provider reported vaccination records. Two socioeconomic status (SES) measures were used: mother’s education and annual family income. Multivariate logistic analyses were conducted. 
Results: False negatives of parental reports against provider records were more than two times higher (p < 0.001) in low SES teens than in high SES teens. In both SES measures, the proportion of HPV unvaccinated teenagers were lowest in the highest SES level in analyses with parental reports. However, it was the opposite in analyses with provider records. Interestingly, regardless of vaccination information source, the HPV unvaccinated rate was highest in the middle SES teens (>12 years, non-college graduates; and above poverty level, but not > $75K). 
Conclusion: A significant social inequality in HPV vaccination among teenagers exists in the United States. The pattern of social inequality in HPV vaccination can be distorted when only parent reported vaccination information is used.

ccJE+Advax is an inactivated cell culture Japanese encephalitis (JE) vaccine formulated with Advax™, a novel polysaccharide adjuvant based on delta inulin. This vaccine has previously shown promise in murine and equine studies and the current study sought to better understand its mechanism of action and assess the feasibility of single dose vaccine protection. Mice immunised with ccJE-Advax had higher serum neutralisation titres than those immunised with ccJE alone or with alum adjuvant. ccJE+Advax induced extraordinarily broad cross-neutralising antibodies against multiple flaviviruses including West Nile virus (WNV), Murray Valley Encephalitis Virus (MVEV), St Louis Encephalitis virus (SLE) and Dengue-1 and -2 viruses. Notably, the DENV-2 cross-neutralising antibodies from ccJE+Advax immunised mice uniquely had no DENV-2 antibody dependent enhancement (ADE) activity, by contrast to high ADE activity seen with DENV-1 cross-reactive antibodies induced by mbJE or ccJE alone or with alum adjuvant. JEV-stimulated splenocytes from ccJE+Advax immunised mice showed increased IL-17 and IFN-γ production, consistent with a mixed Th1 and Th17 response, whereas ccJE-alum was associated with production of mainly Th2 cytokines. There is an ongoing lack of human vaccines against particular flaviviruses, including WNV, SLE and MVEV. Given its ability to provide single-dose JEV protection as well as to induce broadly neutralising antibodies free of ADE activity, ccJE+Advax vaccine could be highly useful in all situations where rapid protection is desirable but ADE needs to be avoided, e.g. during a local outbreak or for use in travellers or the military requiring rapid travel to JEV endemic regions.

Feline infectious peritonitis (FIP), caused by the feline coronavirus (FCoV), is a devastating dis-ease in cats. Based on its antigenicity, FCoV can be divided into two serotypes: FCoV-I and FCoV-II. Furthermore, according to its pathogenicity, FCoV can be divided into feline enteric coronavirus (FECV) and feline infectious peritonitis virus (FIPV). There are numerous factors that affect the pathogenesis of FIP, among which host immunity and viral genetics can play an es-sential role in the development of FIP. Owing to the lack of specific symptoms, existing individual diagnostic methods can only support the suspicion of FIP, and multiple diagnostic methods and test data need to be combined to make a diagnosis. Although there are still no effective FIPV vaccines or commercial drugs available in the market, various studies have shown that some compounds can be used for treatment. Therefore, FIP is no longer incurable in cats

Several COVID-19 platforms have been licensed across the world thus far, but vaccine platforms research that can lead to effective antigen delivery is still ongoing. Here, we constructed AdCLD-CoV19 that could modulate humoral immunity by harboring SARS-CoV-2 antigens onto a chimeric adenovirus 5/35 platform that was effective in cellular immunity. By replacing the S1/S2 furin cleavage sequence of the SARS-CoV-2 Spike (S) protein mounted on AdCLD-CoV19 with the linker sequence, high antigen expression was confirmed in various cell lines. The high levels of antigen expression contributed to antigen-specific antibody activity in mice and non-human primates (NHPs) with single vaccination of AdCLD-CoV19. Furthermore, the adenovirus-induced Th1 immune response was specifically raised for the S protein, and these immune responses protected the NHP against live viruses. While AdCLD-CoV19 maintained neutralizing antibody activity against various SARS-CoV-2 variants, it was reduced to single vaccination for β and ο variants, and the reduced neutralizing antibody activity was restored with booster shots. Hence, AdCLD-CoV19 can prevent SARS-CoV-2 with single vaccination, and the new vaccine administration strategy that responds to various variants can maintain the efficacy of the vaccine.

Since 2015, outbreaks of foot-and-mouth disease (FMD) in the Middle East have been caused by a new emerging viral lineage, A/ASIA/G-VII. In-vitro vaccine matching data indicated that this virus poorly matched (low r1-value) with vaccines that were being used in the region as well as most other commercially available vaccines. The aim of this study was to assess the performance of two candidate vaccines against challenge with a representative field virus from the A/ASIA/G-VII lineage. The results from an initial full dose protection study provided encouraging data for the A/MAY/97 vaccine, while the A22/IRQ/64 vaccine only protected 2/7 vaccinated animals. In view of these promising results, this vaccine was tested in a potency test (PD50) experiment in which 5 cattle were vaccinated with a full dose, 5 cattle with a 1/3 dose and 5 cattle with a 1/9 dose of vaccine. Vaccines were prepared as would be done during an emergency vaccination campaign using a double oil emulsion adjuvant. At 21 days post vaccination these vaccinated cattle and 3 control cattle were subsequently challenged intradermolingually with a field isolate from the A/ASIA/G-VII lineage. All cattle from the full vaccine dose, 4 cattle from the 1/3 vaccine dose and 2 cattle from the 1/9 vaccine dose were clinically protected against challenge with FMDV A/ASIA/G-VII, resulting in a heterologous potency of 6.5 PD50/dose. These data support previous studies showing that a high potency emergency vaccine can protect against clinical disease when challenged with a heterologous strain of the same serotype. Not only the r1-value of the vaccine, but also the homologous potency of a vaccine should be taken into account when advising vaccines to control an outbreak.

This prospective cohort study aimed to evaluate the efficacy of COVID-19 vaccine schemes, ho-mologous versus heterologous vaccine strategies, and vaccine-induced anti-S-RBD-IgG antibody response in preventing COVID-19 among 942 healthcare workers one year after vaccination with the inactivated and/or mRNA vaccines. All participants received the first two primary doses of vaccines, 13.6% of them lacked the dose-3, 50.5% the dose-4, and 90.3% the dose-5. Antibody lev-els increased with the increase in number of vaccine doses and also in heterologous vaccine regi-mens. In both inactive and mRNA vaccines, infection rates were significantly higher in 2-dose-receivers, but lower in 4- or 5-dose receivers and increasing the total number of vaccine doses resulted in more protection against infection: the 3-dose regimen yielded 4.71 times more protection, the 4-dose 11.76 times and 5-dose 38.46 times more protection from COVID-19 infec-tion, compared to any 2-dose vaccination regimens. Antibody levels at the end of the first year of 4- or 5-dose-receivers were significantly higher than 2- or 3-dose-receivers. To conclude; increased number of total vaccine doses and anti-S-RBD antibody levels increased the protection from COVID-19 infection. Therefore, four or more doses are recommended in one year, for effective protection, especially in risk groups.

Vaccination against tick-borne encephalitis (TBE) is based on the use of formalin-inactivated, culture-derived whole-virus vaccines. Immune response following vaccination is primarily directed to the viral envelope (E) protein, the major viral surface antigen. In Europe, two TBE vaccines are available in adult and pediatric formulations, FSME-IMMUN® (Pfizer) and Encepur® (GlaxoSmithKline). Herein, we analyzed the content of these vaccines using mass spectrometry (MS). The MS analysis revealed that the Encepur vaccine contains not only proteins of the whole virus particle, but also viral non-structural protein 1 (NS1). MS analysis of the FSME-IMMUN vaccine failed due to the high content of human serum albumin used as a stabilizer in the vaccine. However, the presence of NS1 in FSME-IMMUN was confirmed by immunization of mice with six doses of this vaccine, which led to a robust anti-NS1 antibody response. NS1-specific western blot analysis detected anti-NS1 antibodies also in sera of humans who received multiple doses of either of these two vaccines; however, most vaccinees who received ≤3 doses were negative for NS1-specific antibodies. The contribution of NS1-specific antibodies to protection against TBE was demonstrated by immunization of mice with purified NS1 antigen, which led to a significant (p < 0.01) prolongation of the mean survival time after lethal virus challenge. This indicates that stimulation of anti-NS1 immunity by the TBE vaccines may increase their protective effect.

Vaccination attitudes among healthcare workers (HCWs) is a vital factor for measuring their level of vaccination uptake and intention to recommend vaccinations to their patients. To our knowledge, no study has been conducted in South Africa to assess hesitancy to influenza vaccines among HCWs. We used questionnaire adapted from Betsch and colleagues to conduct an online and face-to-face cross-sectional study among HCWs at the start of COVID-19 vaccine roll-out prior to the flu season. Main outcome was influenza vaccine hesitancy. We used multivariate logistic regression to assess predictors of influenza vaccine hesitancy. Of 401 participants, 64.5% were women, 49.2% nurses, and 12.5% physicians. A total of 54.9% were willing to accept vaccination, 20.4% were undecided, and 24.7% intended to refuse. Older participants above 17-25 years and physicians were likely to receive the vaccine. Key predictors of vaccine acceptance were confidence in the effectiveness, consideration of benefits and risks, and willingness to be vaccinated to protect others. Influenza vaccine hesitancy was highest in those who did not trust that influenza vaccines are safe. For future flu seasons, tailored education programs targeting younger HCWs and more information about the composition of flu vaccines would be vital to improve vaccine uptake.

Immune complexes (ICs) made of antibody-bound antigens exhibit immunomodulatory activities exploitable in a vaccination strategy to optimize vaccine efficacy. The modulatory effects of ICs are typically attributed to the Fc fragments of the antibody components, which engage Fc receptors, complement and complement receptors on various immune cells. These Fc-mediated functions facilitate the critical interplay between innate and adaptive immune systems to impact the quality and quantity of the elicited adaptive responses. In addition to the Fc contribution, the Fab fragment also plays an immunoregulation role. The antigen-binding domains of the Fab fragment can bind their specific epitopes at high affinity to sterically occlude these antigenic sites from recognition by other antibodies. Moreover, the Fab-mediated binding have been demonstrated to induce allosteric alterations at nearby or distant antigenic sites. In this review article, we survey published studies to illuminate how the immunomodulatory functions of ICs have been investigated or utilized in a vaccination strategy to fight against an array of infectious pathogens, culminating with IC vaccine designs aimed at preventing HIV-1 infection. In particular, we highlight IC vaccine candidates that exploit Fab-mediated steric and allosteric effects to direct antibody responses away or toward the V1V2 domain, the V3 loop, and other antigenic sites on the HIV-1 envelope gp120 glycoprotein. Like other HIV-1 vaccine approaches, the path for IC-based vaccines to reach the clinic faces major hurdles yet to be overcome; however, investigations into this vaccine strategy have provided insights into the multifaceted activities of antibodies beyond their conventional roles in the host defense against HIV-1 and other microbial pathogens.

Schistosomiasis, a disease historically associated with poverty, lack of sanitation and social inequalities, is a chronic, debilitating parasitic infection, affecting hundreds of millions of people in endemic countries. Although schistosomiasis control approach has shown that chemotherapy is capable of reducing morbidity in humans, rapid re-infection is a reminder that the impact of drug treatment on transmission control or elimination initiatives is marginal. In addition, and regardless of more than two decades of well-executed control activities based on large-scale chemotherapy, the disease is expanding in many areas including Brazil. The development of the Sm14/GLA-SE schistosomiasis vaccine is an emblematic open knowledge innovation that has successfully completed Phase I and Phase IIa clinical trials, with Phase II/III trials underway in the African continent and to be followed in Brazil. Discovery and experimental phases were long term achievements leading to a robust collection of data that are strongly supporting the presently ongoing Clinical Phase. This paper reviews the development of the Sm14 vaccine formulated with GLA-SE (Glucopyranosyl Lipid A), from the earlier experimental developments to clinical trials including the recent status of Phase II studies.

Bovine herpesvirus (BoHV)-5 is a worldwide distributed pathogen usually associated with a lethal neurological disease (meningoencephalitis) in dairy and beef cattle resulting in important economic losses due to the cattle industry. Using recombinant glycoprotein D of BoHV-5 (rgD5), we evaluated the long-duration humoral immunity of the recombinant vaccines in a cattle model. Here we report that two doses of intramuscular immunization, particularly with the rgD5ISA vaccine, are superior to iBoHV-5ISA immunization in the induction of long-lasting antibody responses. Recombinant gD5 antigen elicited tightly mRNA transcription of the Bcl6 and the chemokine receptor CXCR5 which mediate memory B cells and long-lived plasma cells in germinal centers (GCs). In addition, using an in-house Enzyme-Linked Immunosorbent Assay (ELISA) we observed higher and earlier responses of rgD5-specific IgG antibody and the upregulation of mRNA transcription of IL2, IL4, IL10, IL15 and IFN-γ cytokines in rgD5 vaccinated cattle, indicating a mixed immune response. We further show that rgD5 immunization provides protection against both BoHV -1 and -5. Our findings indicate that the rgD5-based vaccine represents an effective vaccine strategy to induce an efficient control of alpha-herpesviruses.

Severe Acute Respiratory Syndrome Coronavirus 2 commonly known as SARS-CoV-2 is the utmost challenging pandemic that attracted scientific community to discover therapeutics as well as vaccination solutions to control SARS-CoV-2. Different diagnostic and detection methods have been improved and re-introduced from the previous observations of SERS and MERS. Due to the high mortality rate and fast spread, researchers all around the globe gathered to develop an effective vaccine. The review article summarizes various types of vaccines, mutants of virus, strategies in tackling virus, vaccine development and its global distribution with the focus on the use of mix and match of vaccines to fight the virus. The reported studies depict the design and production of successful COVID-19 vaccines with good efficacy as the selected vaccine population embrace high-risk personages i.e. above the age of 60, frontline workers and other essential service workers. We have targeted at delivering an outline of the determinations devoted to an effectual vaccine for novel Covid-19 that has restricted the domain by means of human health, economy, as well as life.

This proposal was prepared in the very first weeks of 2020 because of the outbreak of COVID-19.There is good reason to suppose that rotavirus vaccine can be used as protection tool to effectively and safely fight and mitigate SARS-CoV-2 infection and the impact caused by COVID-19 in adult humans, due to the development of cross and trained immunity following rotavirus vaccination. Up-to-date, some rotavirus vaccines are available and approved, two of them have a large experience in results and safety. Little experience has been achieved in the use of rotavirus vaccine in adults. However, it can be expected that it would be safe and effective in adults and in the elderly as well. This proposal explains the background.

The presence of a non-structural protein 1 (NS1) in tick-borne encephalitis (TBE) vaccines and the possible induction of an NS1-specific immune response in vaccinated individuals remains a somewhat controversial topic. Previously, we detected the presence of NS1 in Encepur TBE vaccine by mass spectrometry and found the induction of NS1-specific IgG antibodies in mice vaccinated with FSME-Immun TBE vaccine. Here, in this follow-up study, we examined the dynamics and extent of the NS1-specific IgG response in mice vaccinated with these two vaccines in more detail and compared it with the IgG response to the whole virus (WV). Mice were vaccinated at two-week intervals with a total of six doses of each vaccine, and levels of IgG antibodies to TBE virus WV and NS1 were measured by ELISA after each dose. Both vaccines elicited a robust anti-WV IgG response after two doses. The Encepur vaccine did not elicit NS1-specific IgG even after all six doses. In contrast, FSME-Immun vaccine triggered production of NS1-specific IgG after four doses. The results indicate that FSME-Immun is the only vaccine that elicits an NS1-specific antibody response in mice. However, compared to WV-specific IgG, the NS1-specific response is weaker, and a higher number of doses is required to induce detectable levels of NS1-specific IgG antibodies.

World Health Organization (WHO) has announced the monkeypox (MPX) epidemic a global public health emergency due to its re-emergence, remarkable increase in the number of MPX cases worldwide, and its potential spread. This paper introduces the symptoms, complications, and features of MPX; its transmission, diagnosis and testing, vaccines and treatment; MPX and sexually transmitted diseases, especially the human immunodeficiency virus (HIV); possible natural hosts or reservoirs of the monkeypox virus (MPXV). A useful tool for MPX and surgical safety recommendations are presented. The challenges in fighting the MPX epidemic, One Health strategy, and future research are discussed.

An important step towards COVID-19 pandemic control is adequate knowledge and adherence to mitigation measures, including vaccination. We assessed the level of COVID-19 knowledge, attitudes, and practices among residents from an urban informal settlement in the City of Nairobi (Kibera), and a rural community in western Kenya (Asembo). A cross-sectional survey was implemented from April to May 2021 among randomly selected adult residents from a population-based infectious diseases surveillance (PBIDS) cohort in Nairobi and Siaya Counties. Factors associated with the level of COVID-19 KAP, were assessed using multivariable regression methods. COVID-19 vaccine acceptance was 83.6% for the participants from Asembo and 59.8% in Kibera. The reasons cited for vaccine hesitancy in Kibera were safety concerns (34.0%), insufficient information available to decide (18.0%), and a lack of belief in the vaccine (21.0%), while the reasons in Asembo were safety concerns (55.0%), insufficient information to decide (26.0%) and lack of belief in the vaccine (11%). Our study findings suggest the need for continued public education to enhance COVID-19 knowledge, attitudes, and practices to ensure adherence to mitigation measures. Urban informal settlements require targeted messaging to improve vaccine awareness, acceptability, and uptake.

Seasonal influenza is a common cause of hospital admission, especially in older people and those with comorbidities. The objective of this study was to determine influenza vaccine effectiveness (VE) in preventing intensive care admissions and shortening the length of stay (LOS) in hospitalized laboratory-confirmed influenza cases (HLCI) in Catalonia (Spain).A retrospective cohort study was carried out during the 2017-2018 season in HLCI aged ≥ 18 years from 14 public hospitals. Differences in means and proportions were assessed using a t-test or a chi-square test as necessary and the differences were quantified using standardized effect measures; Cohen’s d for quantitative and Cohen’s w for categorical variables. Adjusted influenza vaccine effectiveness in preventing severity was estimated by multivariate logistic regression where the adjusted VE = (1-adjusted odds ratio) ·100%; adjustment was also made using the propensity score.We analyzed 1414 HLCI aged ≥ 18 years; 465 (33%) were vaccinated, of whom 437 (94%) were aged ≥ 60 years, 269 (57.8%) were male and 295 (63.4%) were positive for influenza type B. ICU admission was required in 214 (15.1%) cases. There were 141/1118 (12.6%) ICU admissions in patients aged ≥ 60 years and 73/296 (24.7%) in those aged < 60 years (p<0.001). The mean LOS and ICU LOS did not differ significantly between vaccinated and unvaccinated patients. There were 52/465 (11.2%) in vaccinated cases) ICU admissions in vaccinated cases vs. 162/949 (17.1%) in unvaccinated cases. Patients admitted to the ICU had a longer hospital LOS (mean: 22.4 [SD 20.3] days) than those who were not (mean: 11.1 [SD14.4] days); p<0.001. Overall, vaccination was associated with a lower risk of ICU admission. Taking virus types A and B together, the estimated adjusted VE in preventing ICU admission was 31% (95% CI 1-52; p=0.04). When stratified by viral type, the aVE was 40% for type A (95% CI -11-68; p = 0.09) and 25% for type B (95% CI -18-52; p = 0.21). Annual influenza vaccination may prevent ICU admission in cases of HLCI. A non-significantly shorter mean hospital stay was observed in vaccinated cases. Our results support the need to increase vaccination uptake and public perception of the benefits of influenza vaccination in groups at a higher risk of hospitalization and severe outcomes.

The severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) Omicron variant of concern has been the dominant cause of worldwide COVID-19 cases since 2022. All the Omicron sublineage viruses have demonstrated high transmissibility and an ability to escape vaccine-induced immunity. While first-generation vaccines, including monovalent vaccines, continue to provide protection against severe disease, hospitalization and mortality, their efficacy against Omicron sub variants remains sparse. These vaccines have also been associated with rapidly waning protection against primary COVID-19 and COVID-19 reinfections conferred by evolving Omicron sublineages.. This led to the development and deployment of updated vaccines and the introduction of the bivalent booster. Through this review, we highlight the brief journey of the variants of concern leading to the dominance of Omicron and the effectiveness of the key vaccines against these variants, including the updated (bivalent) boosters.

New Jersey was among the first states impacted by the COVID-19 pandemic, with one of the highest overall death rates in the nation. Nevertheless, relatively few reports have been published focusing specifically on New Jersey. Here we report on molecular, clinical, and epidemiologic observations from the largest healthcare network in the state, in a cohort of vaccinated and unvaccinated individuals with laboratory-confirmed SARS-CoV-2 infection. We conducted molecular surveillance of SARS-CoV-2-positive nasopharyngeal swabs collected in nine hospitals from December 2020 through June 2022, using both whole genome sequencing (WGS) and a real-time RT-PCR screening assay targeting spike protein mutations found in variants of concern (VOC) within our region. De-identified clinical data were obtained retrospectively, including demographics, COVID-19 vaccination status, ICU admission, ventilator support, mortality, and medical history. Statistical analyses were performed to identify associations between SARS-CoV-2 variants, vaccination status, clinical outcomes, and medical risk factors. A total of 5,007 SARS-CoV-2-positive nasopharyngeal swabs were successfully screened and/or sequenced. Variant screening identified three predominant VOC, including Alpha (n =714), Delta (n =1,877), and Omicron (n =1,802). Omicron isolates were further sub-typed as BA.1 (n =899), BA.2 (n =853), and BA.4/BA.5 (n =50); the remaining 614 isolates were classified as “Other”. Approximately 31.5% (1,577/5,007) of the samples were associated with vaccine breakthrough infections, which increased in frequency following the emergence of Delta and Omicron. Severe clinical outcomes included ICU admission (336/5007 = 6.7%), ventilator support (236/5007 = 4.7%), and mortality (430/5007 = 8.6%), with increasing age being the most significant contributor to each (p &lt;0.001). Unvaccinated individuals accounted for 79.7% (268/336) of ICU admissions, 78.3% (185/236) of ventilator cases, and 74.4% (320/430) of deaths. Highly significant (p &lt;0.001) increases in mortality were observed in individuals with cardiovascular disease, hypertension, cancer, diabetes, and hyperlipidemia, but not with obesity, thyroid disease, or respiratory disease. Significant differences (p &lt;0.001) in clinical outcomes were also noted between SARS-CoV-2 variants, including Delta, Omicron BA.1, and Omicron BA.2. Vaccination was associated with significantly improved clinical outcomes in our study, despite an increase in breakthrough infections associated with waning immunity, greater antigenic variability, or both. Underlying comorbidities contributed significantly to mortality in both vaccinated and unvaccinated individuals, with increasing risk based on the total number of comorbidities. Real-time RT-PCR-based screening facilitated timely identification of predominant variants using a minimal number of spike protein mutations, with faster turnaround time and reduced cost compared to WGS. Continued evolution of SARS-CoV-2 variants will likely require ongoing surveillance for new VOCs, with real-time assessment of clinical impact.

There are scarce data regarding flu vaccination among people with HIV infection (PWHIV). The goal of this explorative study is to assess hesitancy toward influenza vaccination in a group of PWHIV during the pandemic. A questionnaire was administered to 219 patients vaccinated at our clinic during the 2020-2021 campaign. It evaluated subjects’ adherence over the last 3 seasonal vaccination campaigns, vaccine confidence, complacency and convenience, and the effect of the pandemic on the choice to vaccinate. The population was divided into two groups: fully adherent (all 3 campaigns, 117 patients) and non-fully adherent (1 or 2 campaigns, 102 patients). Adherence increased in non-fully adherent group in 2020-2021, but the pandemic did not affect the choice. Misbelieves emerged: influenza vaccine was considered protective SARS-CoV-2 (22.8% of total population); almost half of all patients thought influenza vaccine could improve their CD4+ cell level (57.3% in fully adherent, 40.2% in non-fully adherent, p<0.05). A quarter of the non-fully adherent group would not have vaccinated in a location other than our clinic (24.5% vs 11.9% in fully adherent group, p<0.05). Conclusively, offering a secure and private space for vaccination seems to encourage vaccination; healthcare professionals should improve counselling to increase adherence and correct misbeliefs.

Maternal-derived immunity is a critical component for survival and success of offspring in pigs to protect from circulating pathogens like Type 2 Porcine Reproductive and Respiratory Syndrome Virus (PRRSV-2). The purpose of this study was to investigate the transfer of anti-PRRSV immunity to piglets from gilts that received modified-live virus (MLV) alone (TRT 0), or in combination with one of two autogenous inactivated vaccines (AIVs, TRT 1+2). Piglets from these gilts were challenged with the autogenous PRRSV-2 strain at two weeks of age and their adaptive immune response (IR) was evaluated until 4 weeks post inoculation (wpi). The systemic humoral and cellular IR was analyzed in the pre-farrow gilts, and in piglets, pre-inoculation, and at 2- and 4-wpi. Both AIVs partially protected the piglets with reduced lung pathology and increased weight gain; TRT 1 also lowered piglet viremia best explained by the AIV-induced production of neutralizing antibodies in gilts and their transfer to the piglets. In piglets, pre-inoculation, the main systemic IFN-γ producers were CD21α+ B cells. From 0 to 4 wpi, the role of these B cells declined and CD4 T cells became the primary systemic IFN-γ producers. In lungs, CD8 T cells were the primary and CD4 T cells the secondary IFN-γ producers including a novel subset of porcine CD8α-CCR7- CD4 T cells, potentially terminally differentiated CD4 TEMRA cells. In summary, this study demonstrates that maternal AIV vaccination can improve protection of pre-weaning piglets against PRRSV-2; it shows the importance of transferring neutralizing antibodies to piglets; and it introduces two novel immune cell subsets in pigs – IFN-γ producing CD21α+ B cells and CD8α-CCR7- CD4 T cells.

A pandemic happens when a novel influenza A virus is able to infect and transmit efficiently to a new, distinct host species. Although the exact timing of pandemics is uncertain, it is known that both viral and host factors play a role in their emergence. Species-specific interactions between the virus and the host cell determine the virus tropism. These include binding and entering cells, replicating the viral RNA genome within the host cell nucleus, assembling, maturing, and releasing the virus to neighbouring cells, tissues, or organs before transmitting it between individuals. Influenza has a vast and antigenically varied reservoir. In wild aquatic birds, the infection is typically asymptomatic. Avian influenza virus (AIV) can cross into new species, and occasionally, it can acquire the ability to transmit from human to human. A pandemic might occur if a new influenza virus acquires enough adaptive mutations to maintain transmission between people. This review highlights the key determinants AIV must achieve to initiate a human pandemic and describes how AIV mutates to establish tropism and stable human adaptation. Understanding the tropism of AIV may be crucial in preventing virus transmission in humans and may help design vaccines, antivirals and therapeutic agents against the virus.

Background: To our knowledge, the sudden onset of symptomatic pulmonary hypertension after COVID-19 vaccination has not been described. Both cases presented here resulted in functional limitations and likely permanent organ damage. Case Summary: We report two cases of acute onset pulmonary hypertension in previously healthy adult males within three weeks of receiving the second dose of the Pfizer (BNT162b2) mRNA COVID-19 vaccine from different lots. Both patients experienced the sudden onset of severe fatigue and dyspnea on exertion with negative COVID-19 PCR testing. The diagnosis was made by serial transthoracic echocardiography in the first case and by both transthoracic echocardiography and right heart catheterization in the second. Discussion: Pulmonary hypertension is a serious disease characterized by damage to lung vasculature and restricted blood flow through narrowed arteries from the right to left heart. The onset of symptoms is typically insidious, progressive and incurable, leading to right heart failure and premature death. The World Health Organization (WHO) classifies pulmonary hypertension into 5 categories and recently re-defined as a resting mean pulmonary artery pressure greater than 20 mmHg. Sudden onset pulmonary hypertension would only be expected in the settings of surgical pneumonectomy or massive pulmonary emboli with compromise of at least 50% of the lung vasculature.

Six-Transmembrane Epithelial Antigen of the Prostate 1-4 (STEAP1-4) compose a family of metalloproteinases involved in iron and copper homeostasis and other cellular processes. Thus far, five homologs are known: STEAP1, STEAP1B, STEAP2, STEAP3, and STEAP4. In prostate cancer, STEAP1, STEAP2, and STEAP4 are overexpressed while STEAP3 expression is downregulated. Although the metalloreductase activities of STEAP1-4 are well-documented, their other biological functions are not. Furthermore, the properties and expression levels of STEAP heterotrimers, homotrimers, heterodimers, and homodimers are not well-understood. Nevertheless, studies over the last few decades have provided sufficient impetus to investigate STEAP1-4 as potential biomarkers and therapeutic targets for prostate cancer. In particular, STEAP1 is the target of many emerging immunotherapies. Herein, we give an overview of the structure, physiology, and pathophysiology of STEAP1-4 to provide context for past and current efforts to translate STEAP1-4 into the clinic.

To develop a modern plague vaccine, we used hypo-endotoxic Yersinia pestis bacterial ghosts (BGs) with combinations of genes encoding the bacteriophage ɸX174 lysis-mediating protein E and/or holin-endolysin systems from λ or L-413C phages. Expression of the protein E gene resulted in the BGs that retained the shape of the original bacterium. Co-expression of this gene with genes coding for holin-endolysin system of the phage L-413C caused formation of structures resembling collapsed sacs. Such structures, which have lost their rigidity, were also formed as a result of the expression of only the L-413C holin-endolysin genes. Similar holin-endolysin system from phage λ containing mutated holin gene S and intact genes R-Rz coding for the endolysins caused generation of mixtures of BGs that had (i) practically preserved and (ii) completely lost their original rigidity. The addition of protein E to the work of this system shifted the equilibrium in the mixture towards the collapsed sacs. The collapse of the structure of BGs can be explained by endolysis of peptidoglycan sacculi. Immunizations of laboratory animals with the variants of BGs followed by infection with a wild-type Y. pestis strain showed that bacterial envelopes protected only cavies. BGs with peptidoglycan maximally hydrolyzed had a greater protectivity compared to BGs with preserved peptidoglycan skeleton.

There is a growing public health need for effective preventive interventions against dengue, and a safe, effective and affordable dengue vaccine against the four serotypes would be a significant achievement for disease prevention and control. Two tetravalent dengue vaccines, Dengvaxia (Sanofi Pasteur) and DENVax (Takeda Pharmaceutical Company), have now completed phase 3 clinical trials. While Dengvaxia resulted in serious adverse events and is restricted to individuals with prior dengue infections, DENVax has shown, at first glance, some encouraging results. Using the available data for the TAK 003 trial, we estimate, via the Bayesian approach, vaccine efficacy (VE) of the post-vaccination surveillance periods. Although better measurement over long time was expected for the second part of the post-vaccination surveillance, variation in serotype-specific efficacy needs careful consideration. Besides observing that individual serostatus prior to vaccination is determinant of DENVax vaccine efficacy, we also compare the VE estimations for 12 and 18 months and we observe that the efficacy is decreasing over time. The comparison of efficacies over time is informative and very important, bring up the discussion of the role of temporary cross-immunity in dengue vaccine trials and the impact of serostatus prior to vaccination in the context of dengue fever epidemiology.

Vaccination is the most promising approach for ending or containing the SARS-CoV2 pandemic. However, serious post-COVID vaccine reactions including immunocytopenia (ITP) syndrome has been increasingly reported. Several factors cause increased risks including multiple doses, age-dependent heterogeneity in immune-responses, platelet cross-reactions with microbial components, and Long-COVID syndrome. Thus, in the absence of a widely available specific therapeutics, vigilance is important while more studies are imperative. Using a structured questionnaire sent to different regions in Saudi Arabia, we conducted a comprehensive investigation on the frequency, rates, disease patterns, and patient demographics of post-COVID-19 side effects on febrile patients after three major vaccines. Results indicated the majority administered Pfizer BioNtech vaccine (81%, n=809); followed by AstraZeneca (16%, n=155); and Moderna (3%, n=34). In overall 998 participants, 74% (n=737) had no serious symptoms; however, 26.2% (n=261) revealed typical syndrome. In a focused group of 722, shortness of breath (20%), bruises or bleeding (18%), inattention (18%), GIT symptoms (17.6%), skin irritation (8.6%), and anosmia and ageusia (8%) were the most prominent. The onset time was mostly in 1-3 days in 49% (n=128), followed by 4-7 days in 21.8% (n=57), 8-14 days in 16.5% (n=43), and more than a month in 12.6% (n=33). The onsets occurred mostly after the first, second, or both doses 9%, 10%, and 7%, respectively. The frequency of symptoms was significantly higher among after Moderna ® vaccine (P-value = 0.00006) and it was significantly lower in participants who received Pfizer (P-value 0.00231). We did not find significant difference in symptoms related to differences in regions. Similarly, the region, age, gender, education, and nationality had no influence in the dose and onset timings. The findings of this study have significant clinical implications in disease management strategies, preventive measures, and vaccine development. Future vertical studies would reveal more insights into the mechanisms of post-COVID vaccine syndrome.

Appropriate vaccine selection is crucial in the control of foot-and-mouth disease (FMD). Vaccination can prevent clinical disease and reduces viral shedding, but there is a lack of cross-protection between the seven serotypes and their sublineages, making the selection of an adequately protective vaccine difficult. Since the exact composition of their vaccines is not consistently disclosed by all manufacturers, incompatibility of the strains used for vaccination with regionally circulating strains can cause vaccination campaigns to fail. Here, we present a deep sequencing approach for polyvalent inactivated FMD vaccines that can identify all component strains by their genome sequences. The genomes of all strains of a commercial pentavalent FMD vaccine were de-novo assembled and the vaccine composition determined semi-quantitatively. The genome assembly required high stringency parameters to prevent misassemblies caused by conserved regions of the genome shared by related strains. In contrast, reference-guided assembly is only recommended in cases where the number of strains is previously known and appropriate reference sequences are available. The presented approach can be applied not only to any inactivated whole-virus FMD vaccine, but also to vaccine quality testing in general and allows for better decision-making for vaccines with unknown composition.

The global COVID-19 pandemic has affected all spheres of human life, resulting in millions of deaths and overwhelming medical facilities. Moreover, the world has witnessed great financial hardship because of job losses resulting in economic havoc. Many sections of society have contributed in different ways to slow the spread of the virus and protect public health. For example, medical scientists are praised for their efforts to develop COVID-19 vaccines. Clinical trials have shown that the COVID-19 vaccines are highly effective in preventing symptomatic COVID-19 infections. However, many people around the world have been hesitant to get vaccinated. Vaccine misconceptions have emerged and increased due to a combination of factors, including the availability of information on the Internet and the influence of celebrities and opinion leaders. In this context, we have analyzed ChatGPT responses to relevant queries on vaccine misconceptions. The positive responses and supportive opinions provided by the AI chatbot could be instrumental in shaping people’s perceptions of vaccines and in encouraging users to get vaccinated and reduce misconceptions.

Objective: Despite increasing interest in understanding factors influencing awareness, knowledge, and acceptability of the human papilloma virus (HPV) vaccine among Latino parents to date, limited information is available specific to Latino fathers living in the United States. Methods: This descriptive qualitative study explored Latino fathers’ awareness, knowledge, and acceptability of the HPV vaccine for their adolescent children. Data were collected through individual, semi-structured interviews and analyzed using a hybrid method of thematic analysis that incorporated deductive and inductive approaches. Results: Nineteen, majority foreign-born Latino fathers (63.2%; n = 12) fathers of male and female adolescents participated in the study. Four main themes and two subthemes emerged from the analyses. Results found fathers’ low awareness and knowledge of HPV and the HPV vaccine. Results also identified fathers’ positive attitude toward vaccines in general. Moreover, results revealed fathers’ trust in healthcare providers. This trust translated into an increased willingness to vaccinate their children against HPV if recommended by their child’s primary healthcare provider. Conclusion: Findings indicate the need for increased efforts to raise awareness and knowledge among Latino fathers of HPV and the HPV vaccine. In addition, findings underscore the critical role of healthcare providers’ recommendation of the HPV vaccine. Given the limited research focused on Latino fathers, this study’s findings are valuable in building a knowledge foundation needed for developing future studies and interventions to promote the HPV vaccine by targeting Latino fathers living in the United States. Future research should quantify Latino fathers' awareness, knowledge, and acceptability of the HPV vaccine for their children, and preferences for educational interventions to promote HPV vaccination.

The reason for this dissertation is to establish the effects of vaccination on the elderly (>65 years old) in Hong Kong in reducing flu infection. Influenza vaccine uptake in the elderly (˃65 years old) in Hong Kong significantly increased in 2003 after the SARS epidemic. The exact impacts of influenza vaccine among the elderly in Hong Kong are a subject of contention. The effectiveness of the influenza vaccine comes from observed studies which may be prejudiced since it is difficult to identify and justify the evidence. A review of various literatures has shown that influenza causes serious illness and death particularly highly vulnerable groups such as adults aged 65 years and above. Therefore, more efforts should be initiated to reduce mortality caused by influenza among the elderly. According to the WHO (2005), vaccination is among the most effective approach for preventing death associated with influenza to vulnerable groups such as the elderly.

Foot-and-mouth disease virus (FMDV) causes the highly contagious foot-and-mouth disease, which is characterized by the appearance of vesicles in and around the mouth and feet of cloven-hoofed animals. BHK21 cells are the cell line of choice for the propagation of FMDV for vaccine production world-wide but vary in their susceptibility for different FMDV strains. Previous studies showed that the FMDV resistance of a certain BHK cell line can be overcome by using a closely related but permissive cell line for the pre-adaptation of the virus, but the adapted strains were found to harbor several capsid mutations. In this study, these adaptive mutations were introduced into the original Asia-1 Shamir isolate individually or in combination to create a panel of 17 Asia-1 mutants by reverse genetics and examine the effects of the mutations on receptor usage, viral growth, immunogenicity and stability. A single amino acid exchange from glutamic acid to lysine at position 202 in VP1 turned out to be of major importance for productive infection of the suspension cell line BHK-2P. In consequence, two traditionally passage-derived strains and two recombinant viruses with a minimum set of mutations were tested in vivo. While the passaged-derived viruses showed a reduced particle stability, the genetically modified viruses were more stable but did not confer a protective immune response against the original virus isolate.

During the SARS-CoV-2 vaccination campaign, people with CF (pwCF) were considered a clinically vulnerable population. However, data on immunogenicity of anti-SARS-CoV-2 vaccines in pwCF are lacking. We conducted a prospective study enrolling all patients aged >12 and followed-up in our CF centre, who received two doses of the BNT162b2 vaccine in March-­­­October 2021. They underwent a blood sample for quantification of antibodies to the SARS-CoV-2 spike protein receptor binding domain immediately before receiving the first dose and after 3 and 6 months from the second dose. We enrolled 143 patients (median age: 21 years, range: 13-38); of whom 16 had a previous infection. Median antibody titer (interquartile range) after 3 months from vaccination was 1288 U/mL (730-2115) and decreased to 918 U/mL (534-1488) after 6 months (P<0.0001). Median values were higher among previously infected patients as compared to those naïve to SARS-CoV-2 (9107 vs 1229 U/mL at 3 months and 4810 vs 829 U/mL at 6 months, P<0.0001) with no significant differences in the rate of decline over time (P=0.135). All pwCF mounted an antibody response after two-doses of BNT162b2 vaccine that waned at 6 months from vaccination. Age ≥30 years and use of inhaled corticosteroids were associated with a lower humoral response.

Abstract Background COVID-19 vaccination program among Adults in India is one of the highly successful vaccination drives globally. Indian children aged 15–18 years old became eligible for COVID-19 vaccination on 3rd January, 2022 followed by 12-14 years old children on 16th March, 2022. As parents are primary decision-makers for their children, we aimed to assess parents' perceptions and intentions regarding COVID-19 vaccination for children in India. Aim To assess parental perceptions and intention to get COVID-19 vaccination for their children (aged<18 years), Materials and Methods A cross-sectional anonymous web-based survey was designed. Healthcare workers of a tertiary care institute in Eastern U.P. having any children aged <18 years were the study population. They were recruited through snowball sampling and were sent the study questionnaire in Google form through email and WhatsApp. Cross-tabulation was performed by parents' intention to vaccinate their children against COVID-19 virus with socio-demographic characteristics and their risk perception toward COVID-19, trust in the healthcare system, and their history of vaccine hesitancy behavior routine childhood immunization. Bi-variate analysis was performed to find out the predictors of child vaccination intention among the parents. Results A total of 388 healthcare workers parents (HCWPs) having A child < 18 years of age completed the survey. Mean age of the parents were 40.28 ±11.34 years with majority(97.0%) completing recommended 2 doses of COVIID-19 vaccine. Around 91% of the parents agreed that COVID-19 vaccines are important for child’s health whereas about 89% agreed to the statement that COVID-19 vaccines are effective. A total 356 (91.7%) participants were willing to vaccinate their child against COVID-19, 91.3% of them liked to do so as soon as possible. The factors significantly associated with the stated likelihood of child vaccination among the participants were younger age, female gender, urban residence, absence of any chronic illness, lower monthly income, history of COVID-19 in child and the child/children completed with routine childhood vaccines. Parental concerns mainly centered around vaccine need, safety and side effects. Conclusion The healthcare worker parents(HCWPs) have good knowledge and positive attitude towards COVID-19 vaccination for children. Around 92% of them were willing to vaccinate their children with COVID vaccine currently, which implies very low vaccine hesitancy among the HCWPs . Further longitudinal studies are required to be conducted to assess the trend of parental acceptance of COVID vaccine.

The present study was conducted to evaluate encapsulated essential oils as an alternative anticoccidial in coccidiosis vaccine challenged broiler chickens. A total of 600 day-old male broiler chicks were provided with no-added corn-soybean meal-based control diet or diets that contained either salinomycin or EO at 60 and 120 mg per kg of diet. On day 21, half of the control groups were orally challenged with a coccidiosis vaccine at 25 times higher than the recommended vaccine dose. During 22 to 28 days (i.e., one-week post coccidiosis vaccine challenge), the challenged chickens had decrease (P < 0.05) in body weight gain and feed intake but increase in feed conversion ratio compared with the non-challenged, naïve control chickens. However, dietary EO significantly counteracted (P < 0.05) coccidiosis vaccine-induced depression in body weight gain and feed intake. Increasing dietary EO linearly decreased (P < 0.05) the concentrations of the volatile fatty acids. Dietary SAL and EO affected gut morphology in chickens at 20 days posthatch. Increasing dietary EO linearly (P = 0.073) increased serum catalase activity. Collectively, our study shows that dietary EO increased coccidiosis vaccine-induced growth depression and altered gut physiology in broiler chickens.

We determined the levels of neutralizing antibodies against the SARS-CoV-2 ancestral strain, Delta and Omicron variants of concern (VOCs) in 125 healthcare workers, who received Coro-naVac as their primary vaccination and later received either a single ChAdOx1 or a combination of two consecutive boosters using either two ChAdOx1 doses or a ChAdOx1 or BNT162b2 as the primary and second boosters, respectively, or 2 doses of BNT162b2. The titers 12 weeks after primary vaccination were inadequate to neutralize the all strains. After a single ChAdOx1 boost-er, the levels of neutralization at Day 30 varied significantly, only a small proportion of partici-pants developing neutralizing titers against Omicron at Day 7 and 30. The two doses of ChA-dOx1 as the booster induced lowest activity. A combination ChAdOx1 and BNT162b2 induced greater neutralization than by two doses of ChAdOx1. Two doses of BNT162b2 as the booster had the maximal activity against Omicron VOC.

Generating long-lived mucosal and systemic antibodies through respiratory immunization with protective antigens encapsulated in nanoscale biodegradable particles could potentially decrease or eliminate the incidence of many infectious diseases but requires incorporation of a suitable mucosal immunostimulant. We previously found that respiratory immunization with a model protein antigen (LPS-free OVA) encapsulated in PLGA 50:50 nanoparticles (~380 nm diameter) surface modified with complement peptide-derived immunostimulant 02 (CPDI-02; formerly EP67) through 2kDa PEG linkers increases mucosal and systemic OVA-specific memory T-cells with long-lived surface phenotypes in young, naïve female C57BL/6 mice. Here, we determined if respiratory immunization with LPS-free OVA encapsulated in similar PLGA 50:50 microparticles (~1 μm diameter) surface modified with CPDI-02 (CPDI-02-MP) increases long-term OVA-specific mucosal and systemic antibodies. We found that, compared to MP surface modified with inactive, scrambled scCPDI-02 (scCPDI-02-MP), intranasal administration of CPDI-02-MP in 50 μL sterile PBS greatly increased titers of short-term (14 days post-immunization) and long-term (90 days post-immunization) antibodies against encapsulated LPS-free OVA in nasal lavage fluids, bronchoalveolar lavage fluids, and sera of young, naïve female C57BL/6 mice. Thus, surface modification of biodegradable microparticles with CPDI-02 is likely to increase long-term mucosal and systemic antibodies against encapsulated protein antigen after respiratory and possibly other routes of mucosal immunization.

Healthy human subjects develop spontaneous CD8+ T cell responses to melanocyte antigens (MA) expressed by normal melanocytes, such as Tyrosinase, MAGE-A3, Melan/Mart-1, gp100, and NY-ESO-1. This natural autoimmunity directed against melanocytes might confer protection against the development of malignant melanoma (MM), where MA are present as overexpressed tumor-associated antigens. Consistent with this notion we report here that functional T cell reactivity to MA was found to be diminished in untreated MM patients: while 57.5% of healthy controls (n=40) exhibited high-frequency MA-specific T cell reactivity ex vivo, such was detected in only 12% of the untreated MM patients (n=24). Three lines of evidence suggest that the MA-reactive T cells present in healthy subjects undergo exhaustion once MM establishes itself. First, only the MA-specific T cell reactivity was affected in the MM patients; that to third party recall antigens was not. Second, in these patients, the residual MA-specific T cells, unlike third party antigen reactive T cells, were functionally impaired, showing a diminished per cell IFN-γ productivity. Third, successful immunotherapy with AGI-101H melanoma vaccine restored natural CD8+ T cell autoimmunity to MA in 85% of the vaccinated patients (n= 27). The role of natural T cell autoimmunity to tumor-associated MA is discussed based on discrete levels of T cell activation thresholds.

Nasal cavity is a primary checkpoint for the invasion of several respiratory pathogens. Numerous pathogens including SARS-CoV-2, S. pneumonia, S. aureus, etc., adhere to the nasal epithelium or mucus to invade and trigger an infection. IgA serves as the first line of defense against foreign antigens and pathogens. They exhibit cross-reactivity against a diverse variety of antigens through immune exclusion, which intercepts the invasion of pathogens through the mucosal lining. Advances in intranasal immunization technology underscore the elevated neutralizing IgA levels at local and distal mucosa in contrast to the parenteral vaccines. This review highlights the adjuvants that induce IgA class switching and the challenges of maintaining nominal IgA levels at the mucosal surface. Finally, the review features the paradigm-shifting of conventional immunization techniques to IgA-inducing vaccines to enhance protection against homologous and heterologous pathogens.

Background: Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory infection globally. There are vaccines in pipeline to prevent it but a systematic review on immunogenicity and safety of vaccine is lacking. Methods: This systematic review of RSV vaccine clinical trials was undertaken using 4 databases. Searches were conducted using both controlled vocabulary terms such as ‘Respiratory Syncytial Virus, Human’, ‘Respiratory Syncytial Virus Infections’, ‘Respiratory Syncytial Virus Vaccines’, ‘Immunization’, ‘Immunization Programs’ and ‘Vaccines’ and corresponding text word terms. The searches for published papers were limited to clinical trials published from January 2000 to August 6th, 2018. RSV infection case was defined as RSV associated medically attended acute respiratory illness (MAARI) or RSV infection by serologically-confirmed test (Western Blot) during the RSV surveillance period. We calculated the relative risk of each vaccine trial with RSV infection case. Results: Of 4395 publications, 24 were included and data were extracted covering 4 major types of RSV vaccine candidates, these being live-attenuated/chimeric (n=9), recombinant-vector (n=10), subunit (n=1) and nanoparticle vaccines (n=4). For RSV infection cases, 7 trials were involved and none of them showed a vaccine-related increased MAARI during RSV surveillance season. Conclusion: LID ∆M2-2, MEDI M2-2, and RSVcps2 (live-attenuated) were considered the most promising vaccine candidates in infant and children. In the elderly, a nanoparticle F vaccine candidate was considered as a potential effective vaccine. Although no promising vaccine was identified from pregnant-women test, RSV F-024 subunit vaccine candidate and an RSV F nanoparticle vaccine showed encouraging results in healthy non-pregnant women.

Mast cells are long-lived, granular, myeloid-derived leukocytes that have significant protective and repair functions in tissues. Mast cells sense disruptions in the local microenvironment and are first responders to physical, chemical and biological insults. When activated, mast cells release growth factors, proteases, chemotactic proteins and cytokines thereby mobilizing and amplifying the innate and adaptive immune system. Mast cells are therefore significant regulators of homeostatic functions and may be essential in microenvironmental changes during pathogen invasion and disease. During infection by helminths, bacteria and viruses, mast cells release antimicrobial factors to facilitate pathogen expulsion and eradication. Mast cell-derived proteases and growth factors protect tissues from insect/snake bites and exposure to ultraviolet radiation. Finally, mast cells release mediators that promote wound healing in the inflammatory, proliferative and remodeling stages. Since mast cells have such a powerful repertoire of functions, targeting mast cells may be an effective new strategy for immunotherapy of disease and design of novel vaccine adjuvants. In this review, we will examine how certain strategies that specifically target and activate mast cells can be used to treat and resolve infections, augment vaccines and heal wounds. Although these strategies may be protective in certain circumstances, mast cells activation may be deleterious if not carefully controlled and any therapeutic strategy using mast cell activators must be carefully explored.

Abstract: Diabetes mellitus (DM) is associated with severe COVID-19 infection and complications. This study assessed COVID-19 vaccine acceptance and hesitancy in diabetes and explored reasons for nonvaccinating. This was a web-based cross-sectional survey using a mixed-method approach conducted between March-May 2021 corresponding to most SSA countries' early vaccine rollout period. Participants were those aged ≥18 years with self-reported DM in 11 Sub-Saharan African (SSA) countries. Responses to comments on reasons for vaccine hesitancy and facilitators for vaccine uptake were analyzed. Of the 73 participants with DM, 65.8% were males older than 35 years (86.3%), had post-secondary education (90%), and a significant proportion was from South Africa (39.7%), Nigeria (28.8%) and Ghana (13.7%). 64.4% had COVID-19 symptoms, 46.6% were tested for COVID-19, of which 19.2% tested positive. Few participants (6.8%) had taken the COVID-19 vaccination, 65.8% were willing to take the vaccine, while 26.0% either refused or hesitated to take the vaccine. The main reasons identified for not taking the vaccine were: advice from religious leaders, concerns about the vaccine safety, its effects, and efficacy, mistrust of the pharmaceutical companies, the conspiracy theories around the vaccines, the process of production, and the personal belief of the participants. However, participants stated they would take the vaccine if given more education about it, receive positive feedback from those vaccinated, are rewarded for taking the vaccine or if vaccination becomes a condition for travel and employment. The findings of this study showed that uptake of the COVID-19 vaccine was very low in this high-risk group. It is imperative that efforts to increase the uptake of vaccines, such as the provision of education and relevant information, are made.

The 10-valent pneumococcal vaccine was introduced in Pakistan’s Expanded Program on Immunization (EPI) in 2013 as a 3+0 schedule without catchup. We conducted three annual cross-sectional surveys from 2014-2016 to measure vaccine-type (VT) carriage in infants from a rural part of Pakistan. Nasopharyngeal specimens were collected by random sampling of infants from 2 union councils of Matiari. Samples were then transported to Infectious Disease Research Laboratory (IDRL) at the Aga Khan University within 6-8 hours of collection. Serotypes were established using sequential multiplex PCR. Of the 665 children enrolled across three surveys, 547 were culture positive for pneumococcus. VT carriage decreased from 21·8% in 2014 to 12·7% in 2016 (p-value for trend <0·001). Those who were not vaccinated or partially vaccinated were found to be at higher risk of carrying a VT serotype (aOR 2·53, 95% CI 1·39, 4·63 for non-vaccinated) and (aOR 3·35, 95% CI 1·82, 6·16 for partially vaccinated). On the other hand, being enrolled in the most recent survey was negatively associated with VT-carriage (aOR 0·51, 95% CI 0·28, 0·93). We found that PCV10 was effective in decreasing the carriage of vaccine-type serotypes in Pakistani infants.

A major advance of drug discovery and targeted therapy directed to cancer cells may be achieved by exploitation and immunomodulation of their unique biological property. This re-view summarizes our efforts to develop novel chemo-thermo-immuno-therapy (CTI therapy) by conjugating a melanogenesis substrate, N-propionyl cysteaminylphenol (NPrCAP: amine analog of tyrosine), with magnetite nanoparticles (MNP). In our approach, NPrCAP provides a unique drug delivery system (DDS) because of its selective incorporation into melanoma cells. It also functions as a melanoma-targeted therapeutic drug because of its production of highly reactive free radicals (melanoma-targeted chemotherapy). Moreover, utilization of MNP is a platform to develop thermo-immunotherapy because of heat shock protein (HSP) generation upon exposure to an alternating magnetic field (AMF). The feasibility of our approach was successfully shown in experimental in vivo and in vitro mouse melanoma models and in preliminary clinical trials to a limited number of advanced melanoma patients.

Influenza virus infection causes severe respiratory illness in people worldwide, disproportionately affecting infants. The immature respiratory tract coupled with the developing immune system is thought to synergistically play a role in the increased disease severity in younger age groups. Although vaccines remain the best solution for protecting this vulnerable population, no vaccines are available for those under 6 months, and for infants aged 6 months to 2 years, the vaccine elicits a dampened immune response. Dampened immune responses may be due to unique features of the infant immune system and a lack of pre-existing immunity. Unlike older children and adults, the infant immune system is Th2 skewed and has less antigen presenting cells and soluble immune factors. Paradoxically, we know that a person’s first infection with the influenza virus during infancy or childhood leads to the establishment of life-long immunity toward that particular virus strain. This is called influenza imprinting. To provide better protection against influenza virus infection and disease in infants, more research must be conducted to understand the imprinting event. We contend that by understanding influenza imprinting in the context of the infant immune system and the infant’s immature respiratory tract, we will be able to design more effective influenza vaccines for both infants and adults. Working through the lens of imprinting, using infant influenza animal models such as mice and ferrets, which have proven useful for infant immunity studies, we will gain a better understanding of imprinting and its implications regarding vaccine design. This review examines literature regarding infant immune development, current vaccine strategies, respiratory development, and the importance of researching the imprinting event in infant animal models to develop more effective and protective vaccines for young children.