The two major global immunisation agenda framings (Missed Opportunity for Immunisation, MOI vs Immunisation Defaulting) are interchangeably and inappropriately used in public health research and practice with flawed or misleading strategies recommended and adopted in various settings globally. This is evident in the fact that many opportunities to adopt evidence/findings from immunisation coverage research in policy are grossly missed. Ineffectiveness of inappropriate interventions from biased evidence can discourage and mislead the governance to make radical decisions by discretion. This could be the reason for the inability of low-and middle-income countries to vaccinate 80% of their children and otherwise; this also poses a global health threat to capable nations. The current guideline and information on MOI and immunisation defaulting appear insufficient and a little clarification on it would assist forerunners in immunisation to achieve measurable progress in ensuring good coverage especially in low-and middle-income countries. Consequently, this paper is aimed at addressing this issue in immunisation practice with appropriate recommendations. Optimistically, this will stimulate further discussions, streamline differences, and gear global immunisation governance on the subject matter, to achieve the target coverage by 2030 in low-and middle-income countries.

Influenza is a disease that poses a significant health burden worldwide. Vaccination is the best way to prevent influenza virus infections. However, conventional vaccines are only effective for a short period of time due to the propensity of influenza viruses to undergo antigenic drift and antigenic shift. The efficacy of these vaccines is uncertain from year-to-year due to potential mismatching between the circulating viruses and vaccine strains, mutations arising due to egg adaptation, and potential contamination of the vaccine virus stock. Subsequently, the inability to store these vaccines long-term and vaccine shortages are challenges that need to be overcome. Conventional vaccines are also less effective for certain populations, including the young, old, and immunocompromised. This warrants for diverse efficacious vaccine developmental approaches, involving both active and passive immunization. As opposed to active immunization platforms (requiring the use of whole or portions of pathogens as vaccines), the rapidly developing passive immunization involves administration of either pathogen-specific or broadly acting antibodies against a kind or class of pathogens as a prophylactic treatment to corresponding acute infection. Several antibodies with broadly acting capacities have been discovered that may serve as means to suppress influenza viral infection and allow the process of natural immunity to engage opsonized pathogens whilst boosting immune system by antibody-dependent mechanisms that bridge the innate and adaptive arms. By that, passive immunotherapeutics approach assumes a robust tool that could aid control of influenza viruses. In this review, we comment on some improvements in influenza management and promising vaccine development platforms, with emphasis on the capacity of passive immunotherapeutics especially when coupled with the use of antivirals in the management of influenza infection.

The COVID-19 pandemic has raised questions about the possible cross immunity resulting from common vaccination programs and SARS-CoV-2 infection. Therefore, the Spanish Obstetric Emergency group performed a multicenter prospective study on the vaccination status of Influenza and Tdap (diphtheria, tetanus and pertussis vaccine boost administered in adulthood) in consecutive cases of SARS-CoV-2 infection in a pregnancy cohort, in order to assess its possible association with the clinical presentation and severity of symptoms of SARS-CoV-2 infection, as well as to determine the factors that may affect vaccination adherence. 1,150 SARS-CoV-2 positive pregnant women from 78 Spanish hospitals were analyzed: 183 had not received either vaccine, 23 had been vaccinated for Influenza only, 529 for Tdap only and 415 received both vaccines. No association was observed between the vaccination status and the clinical presentation of SARS-CoV-2 infection and/or the severity of symptoms. However, a lower adherence to the administration of both vaccines was observed in the Latin-American subgroup. Based on the results above, we reinforce the importance of maternal vaccination programs in the actual pandemic. Health education campaigns should be specially targeted to groups less likely to participate in these programs, as well as for a future SARS-CoV-2 vaccination campaign.

Immune checkpoint blockade therapy has shown successful clinical outcomes in multiple human cancers. In dogs, several types of tumors resemble human tumors in many respects. Therefore, several groups have developed the anti-dog programmed cell death ligand 1 (dPD-L1) monoclonal antibodies (mAbs) and showed efficacy in several canine tumors. To examine the abundance of dPD-L1 in canine tumors, anti-dPD-L1 diagnostic mAbs for immunohistochemistry are required. In this study, we immunized the peptide in the dPD-L1 intracellular domain, and established anti-dPD-L1 mAbs, L1Mab-352 (mouse IgG1, kappa) and L1Mab-354 (mouse IgG1, kappa). In enzyme-linked immunosorbent assay, L1Mab-352 and L1Mab-354 showed high binding affinity to the dPD-L1 peptide, and the dissociation constants (KD) were determined as 6.9 ×10-10 M and 7.2 ×10-10 M, respectively. Furthermore, L1Mab-352 and L1Mab-354 were applicable for the detection of dPD-L1 in immunohistochemical analysis in paraffin-embedded dPD-L1-expressed cells. These results indicated that L1Mab-352 and L1Mab-354 are useful for detecting dPD-L1 in immunohistochemical analysis.

Pakistan is one of the few countries where poliovirus transmission still persists, despite intensive efforts to eradicate the disease. Adequate vaccination coverage is essential to achieve polio eradication, but misconceptions about polio vaccines have hindered vaccination efforts. To address this issue, we conducted a mixed-methods study to explore knowledge and perceptions regarding polio disease and immunization in high-risk areas of Pakistan. We collected quantitative data from 3780, 1258, and 2100 households in Karachi, Bajaur, and Pishin, respectively, and supplemented this with qualitative data from focus group discussions and in-depth interviews. Our findings reveal a high level of awareness about polio and its immunization; however, misperceptions about the polio vaccine persist, leading to vaccine refusal for both polio and routine immunization. Our study provides up-to-date data on knowledge and perceptions of polio and its immunization and identifies critical gaps. These findings can inform the development of future strategies and innovative approaches to improve the success of the polio program in Pakistan.

Background: Paracetamol may be use as antipyretic agent for the treatment of fever, as well as an analgesic in the treatment of mild to moderate pain on post vaccination in infants. The use of Paracetamol during fever may be or may not be recommended since it may alter natural human body immune response although it may reduce pain. Objectives: This study described the relevancy of Paracetamol use post infants vaccination based on data collection systematic review analyses. This study aims to describe the effectiveness of breastfeeding in reducing pain and Paracetamol in reducing fever and pain post infants vaccination. Data Sources and Study Selection: Electronic literature search by hand searching six (6) databases which include Ovid LWW Total Access Collection and Medline, CINAHL (Cumulative Index to Nursing and Alled Health Literature) Plus with Fulltext, Science Direct, Proquest Dissertations and Theses, Proquest Education Journal and Proquest Health and Medical Complete. Additionally, manual reference checks of all articles on Paracetamol and breastfeeding post infants vaccination published in English Language between 1978 and 2017. Two level of screening were used on 9614 citations which include screening of abstracts and titles followed by full text screening. Data Synthesis: Data synthesis were tabulated into study characteristics, quality and effects. Authors of trials were not contacted for further details or provision of original data if the published report contained insufficient information. The study findings, as reported by the authors, were included in this review. The data in this research cannot be pool due to not enough data regarding odd ratio or relative risk as well as confidence interval in each study. Results: Systematic review of breastfeeding included three (3) studies from 9614 of database searching. The reviews of all these three (3) studies found significant benefit from breastfed in pain score and duration of crying as well as behavioral changes. None study stated the unbeneficial of breastfeeding before, during and after immunization. Meanwhile, systematic review of Paracetamol effectiveness included four (4) studies from 1177 of database searching. The reviews of two (2) studies found significant benefit from prophylaxis Paracetamol in fever and only one (1) study found significant benefit from prophylaxis Paracetamol in fussiness. On the other hand, there was one (1) study found not signifiant benefit from prophylaxis Paracetamol in fever. Other than that, there were two (2) studies evaluate the safety of prophylactic Paracetamol which revealed different outcomes, in which study by Prymula et. al. in 2009 found that antibody responses to several antigens were reduced significantly, and the other study by Uhari et. al. in 1988 found that antibody titres to DTP bacteria of placebo and PCM not differ significantly. Thus, Paracetamol seems to be not relevant post infants vaccination and breastfeeding was found to be beneficial post infants vaccination. Conclusions: The relevancy of giving Paracetamol post all types of vaccination may be questionable since the safety issue of this intervention may be arised. Breastfeeding before, during and after immunization are recommended for pain reduction as it was proved effectively. Finally, in deciding Paracetamol to be of rational use following infants immunization, it may need for further research which include in depth quantitative and qualitative studies to identify specific problem and causes regarding this issue.

Studies evaluating candidate tick-derived proteins as anti-tick vaccines in natural hosts have been limited due to high costs. To overcome this problem, animal models are used in immunization tests. The aim of this article was to review the use of rabbits as an experimental model for the evaluation of tick-derived proteins as vaccines. A total of 57 tick proteins have been tested for their immunogenic potential using rabbit as model for vaccination. The most commonly used rabbit breeds were New Zealand (73.8%), Japanese white (19%), Californians (4.8%) and Flemish lop-eared rabbit (2.4%). Anti-tick vaccines efficacy resulted in up to 99.9%. Haemaphysalis longicornis (17.9%) and Ornithodoros moubata (12.8%) were the most common tick model in vaccination trials. Experiments in rabbits have revealed that some proteins (CoAQP, OeAQP, OeAQP1, Bm86, GST-Hl, 64TRP, serpins and voraxin) can induce immune responses against various tick species. In addition, in some cases it was possible to determine that the vaccine efficacy in rabbits was similar to experiments performed in natural hosts (e.g. Bm86, IrFER2, RmFER2, serpins and serine protease inhibitor). In conclusion, results have shown that prior to performing anti-tick vaccination trials using natural hosts, rabbits can be used as suitable experimental models for these studies

Poliomyelitis, commonly known as “polio” is a paralytic and perilous disease caused by the poliovirus. Due to its highly contagious nature, the virus was a challenge to the world in the late 1980s. . Since 1988 the collective work of the Global Polio Eradication Initiative (GPEI), Centre for Disease Control and Prevention (CDC), and World Health Organization (WHO) through immunizations, communication awareness, and monitoring have helped the world exonerate polio. The mission of polio-free Pakistan was herculean and had confronted enormous challenges in different ways but came out with positive results. In 2019, with only two remaining polio-endemic countries, Pakistan and Afghanistan, GPEI launched an “Endgame strategy 2019-2023” which aims to eradicate polio globally, with a targeted focus, especially on polio-endemic countries, the plan emphasizes the early detection of polio cases for complete eradication and to restrict the spread of polio. Pakistan has achieved a milestone in combating polio despite having a web of factors that have thwarted Pakistan’s polio eradication efforts, but this is not the end, the struggle continues until we really get an internationally verified certification of Polio free nation, for this WHO has designed a multidisciplinary strategy 2022-2026 to really end this polio for once and for all.

Background: Maternal influenza vaccination provides effective protection against influenza in-fections in pregnant women and new-borns. In India, the influenza vaccine has not yet been of-fered through immunization programs, owing to the lack of sufficient safety data for Indian pregnant women. Methods: This cross-sectional observational study enrolled 558 women ad-mitted to the obstetrics ward of a civic hospital in Pune. Study-related information was obtained from the participants through interviews using structured questionnaires and hospital records. Univariate and multivariate analysis were used and chi-square with unadjusted and adjusted odds ratio were estimated to account for vaccine exposure and the temporal nature of each out-come, respectively. Results: The protective effect of maternal influenza vaccination against delivering very low birth weight infants was observed. (aOR 2.29, 95% CI 1.03 to 5.58, p=0.03). No association was observed between maternal influenza vaccination for spontaneous abortion (OR 1.42, 95%CI 0.75, 2.68), chorioamnionitis (OR 0.60, 95% CI, 0.1, 3.63), gestational hypertension (OR 1.73, 95% CI 0.72, 4.16) and preterm birth (OR 1.64, 95% CI 0.91, 2.97). Interpretation: These results show that the in-fluenza vaccine administered during pregnancy is safe and has a lower risk of negative birth outcomes.

CC chemokine receptor 6 (CCR6) is a member of the G protein-coupled receptor (GPCR) family that is highly expressed in B lymphocytes, effector and memory T cells, regulatory T cells, and immature dendritic cells. CCR6 has been revealed to have important functions in many pathological conditions, such as cancer, intestinal bowel disease, psoriasis, and autoimmune diseases. The only CCR6 chemokine ligand, CC motif chemokine ligand 20 (CCL20), is also involved in pathogenesis by interacting with CCR6. The CCL20/CCR6 axis is drawing attention as an attractive therapeutic target for various diseases. In this study, we developed novel monoclonal antibodies (mAbs) against human CCR6 (hCCR6) using the peptide immunization method, which are applicable to flow cytometry and immunohistochemistry. The established anti-hCCR6 mAb, clone C6Mab-19 (mouse IgG1, kappa), reacted with hCCR6-overexpressed Chinese hamster ovary-K1 (CHO/hCCR6), HepG2 (human liver carcinoma), and HuH-7 (human differentiated hepatoma) cells in flow cytometry. The dissociation constant (KD) of C6Mab-19 was determined as 3.0 × 10−10 M for CHO/hCCR6, 6.9 × 10−10 M for HepG2, and 1.8 × 10−10 M for HuH-7. Thus, C6Mab-19 could bind to exogenously and endogenously expressed hCCR6 with extremely high affinity. Furthermore, C6Mab-19 could stain formalin-fixed paraffin-embedded lymph node tissues from a patient with non-Hodgkin lymphoma by immunohistochemistry. Therefore, C6Mab-19 is suitable for detecting hCCR6-expressing cells and tissues, and could be useful for pathological analysis and diagnosis.

Background: Since 2000, vaccine coverage in Sub-Saharan Africa (SSA) has surpassed multiple milestones. Its contribution to global health, especially in low-middle-income countries is one of the achievements in global governance of modern medicine, averting 2-3 million child deaths every year. However, in Nigeria, vaccine-preventable-diseases still account for one in eight child deaths before their fifth-year birthday and remains one of the ten countries where 4.3 million children under five are without complete immunization. The reasons for declining childhood vaccine demand are unclear. Therefore, the goal of this contribution is to shed light on the reasons to set a foundation for future interventions. Methods: Four focus group discussions were conducted. The primary targets were mothers of children 0 – 12 months old in Nigeria. A simplified quota sampling approach was used to select mothers in four geographical clusters of Nigeria’s Federal Capital Territory. At least six mothers from each cluster were randomly included, giving a total of 24 participants. An interview guide developed from the 5C psychological antecedence model was used (assessing confidence, complacency, calculation, constraints, collective responsibility); two additional variables were included that had proved meaningful in previous work (religion and masculinity). The data were analyzed using meta-aggregation approach such as framework synthesis, which summarized data in a stepwise fashion. Results: The sample was generally relatively positive towards vaccination. Still, mothers reported low trust in vaccine safety and the healthcare system (confidence). Yet, they had great interest in seeking additional information during antenatal visits (calculation), difficulties in prioritizing vaccination over other equally competing priorities (constraints) and were aware that vaccination translates into overall community health and wellbeing (collective responsibility). They had a bias towards God as ultimate giver of good health (religion) and reported that their husbands played a dominant role in vaccination decision-making (masculinity). Mothers perceived their children vulnerable to disease outbreaks, which motivated them to get them vaccinated (complacency). Conclusion: The 5C model and the added determinants provided a useful qualitative tool for understanding mothers’ vaccination decision-making in low resources settings.

The erythropoietin-producing hepatocellular carcinoma (Eph) receptors are the largest receptor tyrosine kinases family. EphB4 is essential for cell adhesion and motility during embryogenesis. Pathologically, EphB4 is overexpressed and contributes to poor prognosis in various tumors. Therefore, sensitive monoclonal antibodies (mAbs) should be developed to predict the prognosis for multiple tumors with high EphB4 expression, including breast and gastric cancers. This study aimed to develop highly sensitive and specific anti-EphB4 mAbs for several applications using the Cell-Based Immunization and Screening (CBIS) method. EphB4-overexpressed Chinese hamster ovary (CHO)-K1 (CHO/EphB4) cells were immunized into mice, and we established an anti-EphB4 mAb (clone B4Mab-7), which is applicable for flow cytometry, western blotting, and immunohistochemistry. B4Mab-7 reacted with endogenous EphB4-positive breast cancer cell lines, MCF-7 and MDA-MB-468, but did not react with EphB4-knockout MCF-7 (BINDS-52) in flow cytometry. Dissociation constant (KD) values were determined to be 2.9 × 10‑9 M, 1.3 × 10‑9 M, and 3.3 × 10‑9 M by flow cytometric analysis for CHO/EphB4, MCF-7, and MDA-MB-468 cells, respectively. B4Mab-7 detected the EphB4 protein bands from breast cancer cells in western blotting, and stained breast cancer tissues immunohistochemistry. Altogether, B4Mab-7 demonstrated high sensitivity and specificity against EphB4 in various applications.

Overexpression of human epidermal growth factor receptor 2 (HER2) in breast cancer is an important target of monoclonal antibody (mAb) therapy such as trastuzumab. Due to the development of trastuzumab-deruxtecan, an antibody-drug conjugate, the targetable HER2-positive breast cancer patients have been expanded. To evaluate developing modalities using anti-HER2 mAbs, reliable preclinical mouse models are required. Therefore, sensitive mAbs against mouse HER2 (mHER2) should be established. This study developed mHER2 mAbs using the Cell-Based Immunization and Screening (CBIS) method. The established anti-mHER2 mAbs, H2Mab-300 (rat IgG2b, kappa) and H2Mab-304 (rat IgG1, kappa), reacted with mHER2-overexpressed Chinese hamster ovary-K1 (CHO/mHER2) and endogenously mHER2-expressed cell line, NMuMG (a mouse mammary gland epithelial cell) by flow cytometry. Furthermore, these mAbs never recognized mHER2-knockout NMuMG cells. The kinetic analysis using flow cytometry indicated that the dissociation constant (KD) of H2Mab-300 and H2Mab-304 for CHO/mHER2 was 1.2 × 10−9 M and 1.7 × 10−9 M, respectively. The KD of H2Mab-300 and H2Mab-304 for NMuMG was 4.9 × 10−10 M and 9.0 × 10−10 M, respectively. These results indicated that H2Mab-300 and H2Mab-304 could apply to the detection of mHER2 using flow cytometry and may be useful to obtain the proof of concept in preclinical studies.

The Epidermal Growth Factor Receptor (EGFR) overexpression or its mutation mediates the sustaining proliferative signaling in cancers. Human EGFR-targeting monoclonal antibody (mAb) therapy such as cetuximab has been approved for clinical use in patients with colorectal cancers and head and neck squamous cell carcinomas. A reliable preclinical mouse model is essential to further develop the mAb therapy against EGFR. However, a mAb against mouse EGFR (mEGFR) for flow cytometry has not been established. In this study, we developed a specific and sensitive mAb for mEGFR using the Cell-Based Immunization and Screening (CBIS) method. The established anti-mEGFR mAb, EMab-300 (rat IgG1, kappa) reacted with mEGFR-overexpressed Chinese hamster ovary-K1 (CHO/mEGFR) and endogenously mEGFR-expressed cell lines, including NMuMG (a mouse mammary gland epithelial cell) and Lewis lung carcinoma cells by flow cytometry. The kinetic analysis using flow cytometry indicated that the dissociation constant (KD) of EMab-300 for CHO/mEGFR and NMuMG was 4.3 × 10−8 M and 1.9 × 10−8 M, respectively. These results indicated that EMab-300 applies to the detection of mEGFR by flow cytometry, and is expected in the use of preclinical study.

This study aimed to evaluate the impact of the COVID-19 pandemic on routine immunization (RI) programs in six Northern Nigerian states: Bauchi, Borno, Kaduna, Kano, Sokoto, and Yobe. This study compared the programmatic data of 2019 and 2020, as well as survey data collected during the pandemic. RI program variables included service delivery, leadership and governance, monitoring and evaluation/supportive supervision, community engagement, vaccine supply chain and logistics, and finance and financial management. Data were analyzed using SPSS (version 23, IBM), student t-test, and structural equation modelling. The results showed that RI programs were affected by the pandemic in terms of reduced meetings and low completion rates of action points in certain states. However, routine immunization support services increased owing to improved monitoring techniques and consistent vaccine deliveries, with fewer reports of stock-outs. The most significant impact of the pandemic was observed on activities coordinated at the healthcare facility level, whereas those at the state level were less impacted. The major challenges encountered during the pandemic included insufficient supplies and consumables, movement restrictions, shortage of human resources, and fear of infection.

There is a lack of information on vaccination for pregnant women in the Brazilian literature. Our aim was to evaluate the data on vaccines recorded on the pregnancy card and knowledge about the importance of vaccination for women admitted for labor in a reference public tertiary maternity unit in Presidente Prudente, São Paulo, Brazil. Vaccine data as prescribed by the National Immunization Program of Brazil (NIP) in prenatal cards for patients in labor from the 45 municipalities of the western region of São Paulo state were obtained. A questionnaire relating to knowledge about the types and importance of vaccination in pregnancy was applied. All vaccines indicated by the NIP were registered in only 12.0% of the prenatal cards, and 33.0% of cards registered any vaccines. In this group, 16.6% were aged between 14 and 21 years, and tetanus and COVID-19 were the most prevalent vaccines that they had heard of during prenatal care. Data on vaccines was poorly recorded in the cards, suggesting a lack of attention and unpreparedness of professionals working in primary care. Our study has countrywide and global relevance, and may be applied mainly in Latin American countries facing similar difficulties and limitations with low rates of vaccination during pregnancy.

Vaccine uptake is one of the indicators that has been used to guide immunization programs. This study aimed to evaluate whether the measles vaccine uptake is predicted by measles vaccine hesitancy. A community-based cross-sectional study was conducted in urban districts in Khartoum state in February 2019. Measles vaccine uptake among children was measured as either fully vaccinated or partially/not vaccinated. The Parents Attitude about Childhood Vaccination (PACV) scale was used to measure measles vaccine hesitancy. Multivariate logistic regression was run to identify the predictors of measles vaccination uptake controlling for sociodemographic variables and the adjusted odds ratios (aORs) with 95% CI were calculated. The receiver operator characteristic (ROC) curve was performed, besides area under the curve (AUC) for the PACV was computed. Data was collected from 495 participants. We found that measles vaccine hesitancy (PACV scores) predicted the uptake of measles vaccine after controlling other potential social confounders such as mother’s age and the number of children (aOR 1.055, 95% CI 1.028-1.028). Additionally, the ROC for the PACV yielded area under the curve (AUC 0.686 (95% CI 0.620-0.751, P <0.001). Our findings show that measles vaccine hesitancy in Sudan directly influences the uptake of the measles vaccine. Addressing the determinants of vaccine hesitancy through communication strategies will improve vaccine uptake.

The Bacillus Calmette-Guerin vaccine (BCG vaccine) designed to prevent tuberculosis in children has been shown to induce a trained immune response in the body to fight against bacteria as well as other parasites and viruses. This knowledge has been reciprocated to generate the idea that this vaccine can also offer protection against severe acute respiratory syndrome coronavirus-2 (SARS-COV-2). Some recent pre-print articles have highlighted that countries with mass BCG immunizations seems to have a lower incidence of coronavirus disease 2019 (COVID-19) compared to those without BCG immunization. There are yet no experimental proof of any such association and the world health organisation (WHO) is currently testing the theory with clinical trials on selected cohorts. Epidemiologists and other scientific experts has expressed both their hope and concern simultaneously regarding the success theory of BCG vaccination to prevent COVID-19. Though its still not verified in any way whether the BCG vaccination can actually prevent COVID-19 or not but we believe a thorough analytical research in this regard is indeed worth a shot.

Meningitis is a severe disease associated with death in children under five with highest rates of infections under age of one. Vaccines for Neisseria meningitides and Haemophilus influenza are used to prevent the main causative agents of meningitis. Administration of H. influenzae type b (Hib) vaccine is recommended at 2, 4 and 6 months with a booster dose at 18 months. N. meningitidis has two commercially available vaccines, the pure polysaccharide is recommended at 24 months meanwhile the protein-conjugated vaccines at 12 months. We sought in this study to examine if coadministering the vaccines for the two main meningitis causing bacteria might be synergistic as a preliminary step towards the possibility of shuffling immunization schedule. So, we coadministered Hib vaccine with commercially available vaccines either quadrate (ACWY) polysaccharide meningococcal (Men) or conjugated meningococcal (Nim) vaccines in Balb/C mice (n = 6/group) and compared to each vaccine administered separately and controls. Thirty-five days post immunization, we measured specific antibodies titers. Hib vaccine increased Men antibody titers significantly for serotypes Y and W. When Hib vaccine was coadministrated with Nim, antibody titer for Y, W and A significantly increased. For serotype C, there was no significant difference in antibody titers among immunized groups. As for effect of meningococcal vaccines on Hib, Men significantly increased Hib antibody titers while Nim had no effect. Collectively, our data suggested that coadministration of Hib and Men or Nim vaccines was safe and had synergistic effect on immune responses elicited to both vaccines. Further studies are needed before immunization schedule modifications. Such immunization schedule recommendation should provide better protection against this life-threatening disease in young children.

(1) Background: Childhood immunization is vital for preventing morbidities and mortalities globally. However, rural Pakistan is facing persistent challenges, particularly after recent global health crises in gauging accurate vaccination coverage estimates. This study aimed to apply a novel Lot Quality Assurance Sampling (LQAS) methodology due to its rapid and reliable estimates of the routine immunization rates among children aged 12-23 months old in Shikarpur, Sindh, and to identify priority areas for future interventions. (2) Methods: A cross-sectional household survey design was adopted for an in-depth assessment of vaccination coverage in a previously under-studied rural context. (3) Results: Data were collected from 1,402 children aged 12-23 months across 47/49 Union Councils in Shikarpur within 141 randomly identified clusters. LQAS was innovatively employed along with GIS Mapping which provided a spatial analysis of the distribution of immunization coverage and the spot map of clusters. The weighted average for fully immunized children was 42.4% after applying Direct Adjustment Method. A steep decline in coverage for each successive vaccine dose was observed, and 39 key priority areas were identified on GIS-based plotting for intensive health interventions. Multivariate Logistic Regression Model further revealed informational gaps and fear of side effects as major barriers to achieving complete immunization. (4) Conclusions: The innovative application of LQAS and GIS Mapping in this study has provided a comprehensive glimpse of its utility in future follow-ups and similar assessments. The findings stress the critical need to tackle the foundational reasons behind the vaccination gaps, with a special focus on enhancing awareness and information dissemination in the key priority areas.

CD39 is involved in adenosine metabolism through conversion of extracellular ATP to adenosine. Because extracellular adenosine plays a critical role in the immune suppression of tumor microenvironment, the inhibition of CD39 activity by monoclonal antibodies (mAbs) is one of the important strategies for tumor therapy. In this study, we developed specific and sensitive mAbs for mouse CD39 (mCD39) using the Cell-Based Immunization and Screening (CBIS) method. The established anti-mCD39 mAbs, which were established by the CBIS method including C₃₉Mab-1 (rat IgG_2a, kappa) and C₃₉Mab-2 (rat IgG_2a, lambda), reacted with not only mCD39-overexpressed Chinese hamster ovary-K1 (CHO/mCD39) but also endogenously mCD39-expressed cell lines, such as L1210 (mouse lymphocytic leukemia) and J774-1 (mouse macrophage-like) cell lines through flow cytometry. Kinetic analyses using flow cytometry indicated that the dissociation constant (K_D) of C₃₉Mab-1 and C₃₉Mab-2 for CHO/mCD39 was 7.3 × 10⁻⁹ M and 5.5 × 10⁻⁹ M, respectively. K_D of C₃₉Mab-1 and C₃₉Mab-2 for L1210 was 3.3 × 10⁻⁹ M and 3.6 × 10⁻¹⁰ M, respectively. Furthermore, C₃₉Mab-1 could detect the lysate of CHO/mCD39 by western blot analysis. These results indicate that C₃₉Mab-1 and C₃₉Mab-2 are useful for the detection of mCD39 in many functional studies.

While there is a coordinated effort around reaching zero dose children and closing existing equity gaps in immunization delivery, it’s important that there is agreement and clarity around how ‘zero dose status’ is defined and what is gained and lost by using different indicators for zero dose status. There are two popular approaches used in research, program design, and advocacy to define zero dose status: one uses a single vaccine to serve as a proxy for zero dose status, while another uses a subset of vaccines to identify children who have missed all routine vaccines. We provide a global analysis utilizing the most recent publicly available DHS and MICS data to compare the number, proportion, and profile of children 12 to 23 months who are ‘penta-zero dose’ (have not received the pentavalent vaccine), ‘truly’ zero dose (have not received the BCG, polio, pentavalent, and measles vaccines), and ‘misclassified’ zero dose children (those who are penta-zero dose but have received at least one other vaccine). Our analysis includes 194,829 observations from 82 low- and middle-income countries. Globally, 14.2% of children are penta-zero dose and 7.5% are truly zero dose, suggesting that 46.5% of penta-zero dose children have had at least one contact with the immunization system. While there are similarities in the profile of children that are penta-zero dose and truly zero dose, there are key differences between the proportion of key characteristics among truly zero dose and misclassified zero dose children, including access to maternal and child health services. By understanding the extent of connection zero dose children may have with the health and immunization system and contrasting it with how much the use of a more feasible definition of zero dose may underestimate the level of vulnerability in the zero dose population, we provide insights that can help immunization programs design strategies that better target the most disadvantaged populations. If the vulnerability profiles of the truly zero dose children are qualitatively different from that of the penta zero dose children, then failing to distinguish the truly zero dose populations, and how to optimally reach them, may lead to the development of misguided or inefficient strategies for vaccinating the most disadvantaged population of children.

This work describes practical immunization of European sea bass (Dicentrarchus labrax) juveniles against viral nervous necrosis virus (VNNV), a betanodavirus causing worldwide mortalities in many fish species. Protection was obtained with the so called spinycterin vehicles consisting in irreversibly DNA-damaged DNA-repair-less E.coli displaying at their surface a downsized antigen. In this work we, i) maximized bacterial expression levels by downsizing the C protein to a fragment (frgC91-220) containing most of its antigenicity, ii) developed an scalable autoinduction bacterial media based in soy-bean increasing membrane display and reproducibility, iii) enriched surface expression by screening different anchors from several prokaryotic origins (anchor+frgC91-220), iv) preserved frgC91-220 antigenicity by inactivating bacteria by irreversible DNA-damage by means of Ciprofloxacin, and v) increased safety using a repair-less E.coli strain as spinycterin chassis. These second generation of spinycterins protected fish against VNNV challenge with partial (Nmistic+frgC91-220) or 100 % (YBEL+frgC91-220 ) protection, in contrast to those fish immunized with frgC91-220 spinycterins. The proposed spinycterin platform has high levels of environmental safety and cost effectiveness, thus providing potential for small fish vaccines for sustainable aquaculture.

Data from the WHO and UNICEF Estimates of National Immunization Coverage (WUENIC) 2022 revision were analyzed to assess the status of routine immunization in the WHO African Region, disrupted by the COVID-19 pandemic. In 2022, the coverage with the first and third dose of diphtheria-tetanus-pertussis containing vaccine (DTP1 and DTP3 respectively) and with the first dose of measles-containing vaccine (MCV1), in the region, was estimated at 80%, 72% and 69%, respectively (all below the 2019 level). Only 13 of the 47 countries (28%) achieved the global target coverage of 90% or above with DTP3 in 2022. From 2019 to 2022, 28.7 million zero-dose were recorded (19.0% of target population). Ten countries of the region accounted for 80.3% of all zero-dose children including the four most populous countries (Nigeria, Ethiopia, Democratic Republic of the Congo, United Republic of Tanzania). Reported administrative coverage greater than WUENIC was found in 19 countries, highlighting routine immunization data quality issues. The WHO African region has not yet recovered from COVID-19 disruptions to routine immunization. It is critical for Governments to ensure that processes are in place to prioritize investments for restoring immunization services, catching-up on vaccination of zero-dose and un-der-vaccinated children and improving data quality.

Abstract Introduction: With the containment of the COVID-19 pandemic in Côte d'Ivoire, efforts were made to seamlessly integrate COVID-19 vaccination into the national immunization program. A collaborative initiative involving UNICEF, WHO, GAVI, and partner organizations resulted in the creation of the COVID-19 Vaccine Integration Mapping Tool. This paper presents a case study documenting the field testing of the Integration Mapping Tool and assessing the integration of COVID-19 vaccination within primary healthcare and routine immunization in Côte d'Ivoire. The study aims to describe the pilot process, gather feedback on tool usefulness and challenges, and establish integration priorities through roadmap development. Methods: Under the guidance of the Ministry of Health and Universal Coverage Cabinet, a workshop was conducted with participants from major health programs to field test the tool. Data analysis was performed using Excel, and the results were presented through tables, heat maps, and line graphs. Results: The first-of-its-kind field test of the Integration Mapping Tool in Cote d'Ivoire showcased its potential to bring key partners together to discuss the current state of integration, to improve transparency about resource allocation resource allocation, and enhance data management for the successful incorporation of COVID-19 vaccination into existing immunization systems. The integration of COVID-19 vaccines in Côte d'Ivoire showed a moderate level of progress, with improvement needed in resource allocation, payment systems, targeting of highest risk groups and vaccine administration. Support should be increased for target population identification, distribution points, quality of care mechanisms, and health personnel training. Health information systems and access to essential medicines were relatively satisfactory. Integration into existing programs, intersectoral collaboration, national health strategy, communication strategy, community participation, and data utilization require improvement. The post-workshop satisfaction survey gave the tool a score of .7 out of 10. Early lessons from Côte d'Ivoire provide guidance for enhancing integration, focusing on data-driven decision-making, collaboration, stakeholder engagement, and effective leadership. Conclusion: The successful field test of the Integration Mapping Tool (IMT) in Côte d'Ivoire marks a groundbreaking milestone, exemplifying the transformative potential of innovative tools in immunization practices. The IMT's application sets a precedent for seamless COVID-19 vaccination integration worldwide, emphasizing data-driven decision-making, collaboration, timing, and leadership. The pilot exercise's success in Côte d'Ivoire was attributed to political commitment, well-facilitated workshops, assessments, and the fact that the team in CI had previously already developed some initial integration plan.

The purpose of this work was to longitudinally investigate the dynamic evolution of vaccine hesitancy towards both COVID-19 and influenza. We followed a cohort of 479 adult patients at Udine Hospital (Italy) having in common a medical history of SARS-CoV-2 infection in 2020, during the first and most impactful pandemic wave. Vaccine attitude was assessed through standardized telephone interviews performed at 12 and 18 months after the acute illness. The background of the survey was represented by COVID-19 vaccination campaign, started with the approval of the first vaccine in December 2020 and bolstered by the introduction of Green Pass in July 2021, in a context where anti-vaccination beliefs and mistrust in healthcare system were rising. The first interview reported the success of the 2020/21 seasonal influenza immunization with 46.8% (224/479) of the participants showing a positive attitude, especially the elderly and people with comorbidities (p&lt; 0.001). The investigation conducted at 18 months showed a drastic drop in flu shot acceptance (30/166, 18.1%), the reluctance being justified by the feeling of protection regardless of prevention (55.8%) and by concerns regarding vaccines safety and efficacy (23.3%). In parallel, a great increase in vaccinations against SARS-CoV2 occurred after the introduction of Green Pass (72.9% vs 26.7%), although only a minority of the participants identified in the restrictions induced by the certification the leading incentive to get immunized (22.3%). Vaccine hesitancy remains a dynamic and complex phenomenon, which is difficult to overcome with incentive or obligatory strategies alone. The purpose of achieving vaccine compliance should always take into account the social and political context, as well as the role of personal opinions and emotions.

Therapeutic vaccine studies should be designed to elicit durable, high magnitude, and efficacious T cell responses, all of which can be impacted by the choice of vaccination schedule. Here, we compare different prime-boost intervals (PBI) in a human papillomavirus (HPV) model using HPV16E6E7 Venezuelan equine encephalitis virus replicon particle (VRP) vaccination to address the optimal boosting schedule, quality of immune response, and overall in vivo efficacy. Six different vaccine regimens were tested with each group receiving booster vaccinations at different time intervals. Analysis of T-cell responses demonstrated a significant HPV16 E7 specific CD8+T cell response with minimally a one-week PBI between antigen re-exposure. Significant E7-specific in vivo cytotoxicity was also observed with longer PBIs. Additionally, longer PBIs led to an enhanced memory recall response to tumor challenge, which correlated with differential expansion of T cell memory subsets. Our findings imply that when using alphavirus vector platforms as a vaccination strategy, a one-week PBI is sufficient to induce high magnitude effector T cells with potent anti-tumor activity. However, longer PBIs lead to enhanced long-term protective anti-tumor immunity. These findings have implications for therapeutic vaccine clinical trials in which shorter intervals of prime-boost regimens may lead to suboptimal durable immune responses.

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.

The COVID-19 pandemic has underscored the importance of swift responses and the necessity of dependable technologies for vaccine development. Our team previously developed a fast cloning system for the modified vaccinia virus Ankara (MVA) vaccine platform. In this study, we report the construction and preclinical testing of a recombinant MVA vaccine obtained using this system. We obtained recombinant MVA expressing the unmodified full-length SARS-CoV-2 spike (S) protein containing the D614G amino acid substitution (MVA-Sdg) and a version expressing a modified S protein containing amino acid substitutions designed to stabilize the protein a in a pre-fusion conformation (MVA-Spf). S protein expressed by MVA-Sdg was found to be expressed and correctly processed and transported to the cell surface, where it efficiently produced cell-cell fusion. Version Spf, however, was not proteolytically processed and despite being transported to the plasma membrane, it failed to induce cell-cell fusion. We assessed both vaccine candidates in prime-boost regimens in the susceptible transgenic K18-human angiotensin converting enzyme 2 (K18-hACE2) mice and in golden Syrian hamsters. Robust immunity and protection from disease was induced with either vaccine in both animal models. Remarkably, the MVA-Spf vaccine candidate produced higher levels of antibodies, a stronger T cell response, and a higher degree of protection from challenge. In addition, the levels of SARS-CoV-2 in the brain of MVA-Spf inoculated mice was decreased to undetectable levels. Those results add to our current experience and range of vaccine vectors and technologies for developing a safe and effective COVID-19 vaccine

Objectives: This study was undertaken to reveal therapeutic effects and the preliminary mechanism of Chinese medicine formula Qianlie Tongli decoction (QTD) in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Methods: A total of 50 male C57BL/6 mice were randomly divided into five groups. All groups except the control group were injected subcutaneously T2 peptide emulsion, which induced the CP/CPPS model. After the induction of CP/CPPS, the model group was given 0.9% NaCl by oral gavage while low-dose, medium-dose, and high-dose groups were treated with Chinese medicine formula. Micturition habits and pain behavior of mice were analyzed for each group. Hematoxylin and eosin staining were used to investigate prostate inflammation. The serum level of tumor necrosis factor-α (TNF-α) was measured by enzyme-linked immunosorbent assay (ELISA) kit. Key findings: Chinese medicine formula significantly reduced the number of urine spots and improved pain response frequency in the medium-dose and high-dose group. The high-dose group showed reduced considerably inflammatory lesion and inflammatory cell infiltration than the low-dose and medium-dose groups. Serum levels of TNF-α in the high-dose group were significantly reduced compared with the model group. Conclusions: The results demonstrated the therapeutic effects of Qianlie Tongli decoction in CP/CPPS mice by analyzing clinically relevant symptoms (urinary tract system, pelvic pain, and prostate inflammation), and preliminary explored the inflammatory-related treatment mechanisms by measuring TNF-α.

Contradictory reports are available on vaccine-associated hyperstimulation of the immune system, provoking the formation of pathological autoantibodies. Despite being interconnected within the same network, the role of the quieter, yet important non-pathological; natural autoantibodies (nAAbs) is less defined. We hypothesize that upon a prompt immunological trigger, also physiological nAAbs exhibit a moderate plasticity. We investigated their inducibility through aged and recent antigenic triggers. Anti-viral antibodies (anti-MMR; n=1739 and anti-SARS-CoV-2 IgG; n=330) and nAAbs (anti-citrate synthase IgG, IgM; n=1739) were measured by in-house and commercial ELISAs, using Croatian (Osijek) anonymous samples with documented vaccination background. Results were subsequently compared for statistical evaluation. Interestingly, IgM isotype nAAb showed a statistically significant connection with anti-MMR IgG seropositivity (p< 0.001 in all cases), while IgG isotype nAAb levels were elevated in association with anti-SARS CoV-2 specific seropositivity (p= 0.019) and in heterogeneous vaccine regimen recipients (unvaccinated controls; vector/mRNA vaccines p= 0.002). Increasing evidence supports the interplay between immune activation and the dynamic expansion of nAAbs. Consequently, further questions may emerge regarding the ability of nAAbs silently shaping the effectiveness of immunization. We suggest re-evaluating the impact of nAAbs on the complex functioning of the immunological network.

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.