Medicine and Pharmacology

Abstract: Objective. To systematically evaluate the interface between vaccination and the gut-brain axis (GBA) in both directions of effect: first, whether vaccines or their components alter GBA biology, including microbiome composition, barrier integrity, cytokine responses, and mitochondrial function; second, whether pre-existing GBA state modifies the response to vaccination; and third, whether either direction bears on neurodevelopmental outcomes or on the adverse events recorded in trials and surveillance. Data Sources. PubMed and Google Scholar were searched directly, and the Walden University Library federated discovery service was used to search its subscribed collections, including MEDLINE, Embase, Cochrane, CINAHL, Scopus and ScienceDirect, from inception to 5 September 2025. Eligibility Criteria. Human and animal studies examining licensed vaccines or vaccine components with measurable outcomes in GBA domains, neurodevelopmental endpoints, or post-marketing adverse events. Results. Of 3,047 records, 60 studies met inclusion criteria in the primary search, with a further 7 identified through a targeted supplementary search to September 2026, giving 67 included studies, listed in Appendix A. Microbiome composition influenced vaccine immunogenicity: higher Bifidobacterium abundance predicted stronger infant antibody responses, and neonatal antibiotic exposure reduced antibody titres to several infant vaccines measured at 7 months of age. Evidence on whether vaccination itself alters the microbiome is limited: one longitudinal adult cohort reported compositional stability, pediatric data are close to absent, and transient shifts have been observed in mice. Animal maternal immune activation models implicated IL-6 and IL-17A pathways in neurodevelopmental alterations, whereas maternal vaccination showed no such association. Cohorts exceeding one million children found no association between autism and the vaccine exposures they measured, principally measles-mumps-rubella vaccination, thimerosal and cumulative antigen count, consistent with a 2025 Danish cohort of aluminium-adsorbed vaccine exposure and a December 2025 WHO advisory reaffirmation. No study identified examined DTaP, hepatitis B or varicella in relation to neurodevelopmental outcomes. Few eligible studies directly assessed barrier or mitochondrial endpoints. Active surveillance quantified specific adverse events, including febrile seizures, intussusception, immune thrombocytopenic purpura, myocarditis (lower with 2023-2024 mRNA formulations), and anaphylaxis. Conclusions. The two directions of effect at this interface are supported to very different degrees, and that asymmetry is the principal finding. Evidence that gut microbiome state modifies vaccine response is moderate in certainty. Evidence on whether vaccination alters gut-brain axis biology, the direction the causal hypotheses in this field assert, is thin rather than negative: barrier, mitochondrial and paediatric data are essentially absent, and the single relevant longitudinal cohort concerns adults receiving COVID-19 mRNA vaccines. Large-scale epidemiology does not support vaccine-attributable increases in autism risk for the exposures those cohorts measured, principally measles-mumps-rubella vaccination, thimerosal and cumulative antigen count; it does not address the microbiome pathway. Several rare adverse events are quantifiable through active surveillance, whereas others remain uncertain signals. Continued active surveillance and transparent risk communication remain essential.

Abstract: Interferon (IFN)-induced protein 6 (IFI6) is an important member of the IFN-stimulated gene (ISG) family, mainly enriched in the inner mitochondrial membrane and endoplasmic reticulum (ER). It plays significant roles in anti-apoptosis, immune regulation, maintenance of mitochondrial homeostasis, antiviral defense, and promotion of tumor progression. At the molecular mechanism level, IFI6 inhibits mitochondrial membrane depolarization, cytochrome c release, and caspase activation. It also regulates the B-cell lymphoma 2 (Bcl-2)/Bcl-2 interacting mediator of cell death (Bim) expression balance, activates the janus kinase (JAK)/signal transducer and activator of transcription (STAT) and phosphatidylinositol 3-kinase-protein kinase B (PI3K-AKT) pathways, and inhibits the degradation of ferroptosis-related proteins solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4), thereby enhancing cell survival and proliferation through multiple pathways. In terms of immune regulation, IFI6 also affects immune cells (such as T/B cells, etc.) and the tumor microenvironment. IFI6 regulates mitochondrial reactive oxygen species (mtROS) and mitochondrial calcium homeostasis, influencing respiratory chain assembly and metabolism. In terms of virus regulation, IFI6 may inhibit the replication of multiple viruses (such as hepatitis B virus (HBV), hepatitis C virus (HCV), SARS-CoV-2, etc.) by inhibiting flavivirus-induced ER invagination, interfering with retinoic acid-inducible gene I (RIG-I)-like receptor signaling pathways, and inhibiting epidermal growth factor receptor (EGFR) kinase activity. In addition, IFI6 is highly expressed in autoimmune diseases and malignant tumors and is associated with proliferation, metastasis, and poor prognosis. In this review, we aim to highlight IFI6 as a potential key target in disease diagnosis and treatment.

Abstract: Background. Allergic airway diseases cause a great burden worldwide. There are a lot of factors which may be important for the risk of development of these diseases. One of them is nasal Staphylococcus aureus carriage which may modulate immune response. The aim of this study was to investigate influence of nasal Staphylococcus aureus carriage on immune response in chronic respiratory allergies related to house dust mite (HDM). Methods. Patients with allergic airway diseases and clinically significant hypersensitivity to HDM and healthy individuals were involved into the study. TNSS, RQLQ, ACT and AQLQ were assessed. A microbiological swab sample was taken from both nostrils for confirmation of Staphylococcus aureus carriage. Nasal smears were obtained for evaluation of eosinophil count. Measurements of IL-10, IL-13, IL-17, IL-22, IL-33 and IFN-γ in serum and nasal lavage fluid were performed by ELISA using commercial kits. Selected patients with allergic airway diseases underwent nasal challenge with Dermatophagoideus pteronyssinus. Results. A tendency that nasal Staphylococcus aureus carriage was more frequent in patients with allergic airway diseases than in healthy individuals was observed. Levels of IL-13, IL-17, IL-33, and IFN-γ in nasal lavage fluid were higher in patients with allergic airway diseases with Staphylococcus aureus carriage than in patients without Staphylococcus aureus carriage. Nasal IL-13 level was independently associated with Staphylococcus aureus carriage (OR 3.18; 95% CI 1.12–8.99; p=0.03) in patients with allergic airway diseases. No significant differences in TNSS, ACT, RQLQ or AQLQ scores were observed between Staphylococcus aureus carriers and non-carriers. Nasal IL-13, IL-17 and IL-33 levels significantly decreased after nasal challenge in Staphylococcus aureus carriers’ group only. Conclusion. Staphylococcus aureus carriage in patients with allergic airway diseases was associated with a distinct local (especially, IL-13) but not systemic cytokine profile and had limited impact on symptoms severity and disease-related quality of life.

Abstract: Background: Mepivacaine hydrochloride is commonly used for digital anaesthesia in United Kingdom podiatric practice, although representative prevalence data are lacking. Published maximum recommended doses vary, and the evidential base of exact mg/kg limits is often unclear. Dose limits remain important safeguards, but they are not individual toxicity thresholds. Methods: This structured narrative review updates a 2021 preprint. The original review searched MEDLINE, Embase, CINAHL and AMED. For this revision, the authors reassessed the earlier evidence base and updated searches of PubMed, reference lists, regulatory sources, product information, and professional guidance through to September 2026. Priority was given to current United Kingdom legislation and product information, systematic reviews, practice advisories and primary pharmacokinetic or clinical studies. This was not a systematic review; formal risk-of-bias appraisal and meta-analysis were therefore not undertaken. Results: Mepivacaine is an intermediate-acting amino-amide local anaesthetic with relatively limited vasodilator activity. Recommended adult doses differ between product information, formularies and textbooks. Treat these limits as conservative population-level safeguards rather than precise toxicity thresholds. Systemic exposure is influenced by total dose, concentration, injection site and speed, accidental intravascular administration, concurrent local anaesthetics and patient factors. Historical paediatric rules based on fractions of an adult dose are unsuitable for contemporary clinical dosing. Safe practice requires the lowest effective dose, incremental injection, dose calculation across all local anaesthetics, readiness to recognise local anaesthetic systemic toxicity and immediate access to an emergency plan. Conclusion: 3% mepivacaine remains a practical option for digital anaesthesia, but neither customary podiatric practice nor a single mg/kg figure is sufficient evidence of safety. Clinicians should follow current product information and legislation, individualise dosing conservatively and maintain competence and preparedness for local anaesthetic systemic toxicity.

Abstract: Current concepts recognize that effective host defense depends on coordinated interactions among innate and adaptive immunity, inflammatory signaling, immunometabolic regulation, and multiple complementary adaptive biological processes. However, far less attention has focused on the regulatory systems that integrate these diverse responses across the evolving phases of the host response. This Review proposes that glucocorticoid receptor alpha (GRα) functions as a systems-level integrative regulator that coordinates immune signaling, antimicrobial competence, mitochondrial bioenergetics, inflammatory regulation, and other adaptive processes according to the temporal phase of homeostatic correction. A central premise is that these phase-specific actions are shaped by dynamic changes in chromatin accessibility and transcription-factor interactions, providing a molecular basis for differential GRα regulation throughout the adaptive response. Rather than functioning solely as a transcriptional regulator of inflammation, GRα coordinates pathogen sensing, NF-κB/AP-1 signaling, immunometabolic adaptation, innate and adaptive immune responses, endothelial and epithelial barrier integrity, lymphatic function, tissue repair, and the transition from early host defense to inflammatory resolution and restoration of physiological homeostasis. These integrated biological processes are organized within the proposed Priming, Modulatory, and Restorative phases of homeostatic correction. By synthesizing evidence across multiple physiological systems, this Review provides a biologically plausible model for understanding how coordinated GRα-dependent regulation may influence immune effectiveness, disease tolerance, host-defense outcomes, and adaptive recovery during infection and critical illness. The proposed model generates testable hypotheses to guide future mechanistic investigation and the development of precision therapeutic strategies.

Abstract: Background: People living with HIV (PLWH) have increased cardiovascular disease (CVD) risk, and dyslipidemia remains a major modifiable factor. Achieving recommended low-density lipoprotein cholesterol (LDL-C) targets can be challenging. Objective: To evaluate the real-world effectiveness and safety of fixed-dose low-dose rosuvastatin/ezetimibe in virologically stable PLWH and explore lipid-lowering kinetics versus an unmatched HIV-negative control cohort. Methods: This retrospective single-center study included 32 PLWH and 43 HIV-negative outpatients receiving rosuvastatin 5 mg plus ezetimibe 10 mg daily. Lipid parameters, CVD risk scores, and safety markers were assessed at baseline, 3 months, and 6 months. Results: In PLWH, LDL-C decreased from 170.7 ± 35.1 to 87.8 ± 24.6 mg/dL at 6 months (p< 0.001), and 53.1% reached guideline-recommended LDL targets. CVD risk scores improved and correlated with LDL-C reduction (D:A:D, r=0.74). Mixed-design ANOVA showed significant group×time interactions for total, LDL, and non-HDL cholesterol: controls achieved most lipid reduction by 3 months, whereas PLWH showed a more progressive decline through 6 months. No treatment-limiting adverse events or viro-immunological deterioration occurred. Conclusions: The combination of low-dose rosuvastatin and ezetimibe proved safe and effective in enhancing lipid profiles and lowering cardiovascular risk in PLWH, including those with metabolic comorbidities. This strategy facilitates achievement of stringent lipid targets outlined in current HIV guidelines, by delivering synergistic LDL reductions, superior to statin monotherapy. The exploratory comparison suggests distinct lipid-lowering kinetics in PLWH versus HIV-negative controls; demographic differences between cohorts warrant cautious interpretation.

Abstract: Functional human humoral immunity remains one of the greatest challenges in humanized mouse research. Although numerous humanized mouse models have been developed, efficient antigen-specific antibody responses remain difficult to reproduce. This review proposes a conceptual framework for evaluating humanized mouse models based on the reconstruction of functional humoral immune modules rather than the presence of individual immune-cell populations. Functional humoral immunity depends on the coordinated reconstruction of functional modules established through productive cognate interactions among immune cells within spatially organized lymphoid microenvironments. Comparative analyses of representative humanized mouse models demonstrate that these functional modules are only partially reconstructed and differ substantially among currently available models. Moreover, the duration of the humoral immunity window—the period during which the functional modules required for humoral immunity remain sufficiently coordinated to support productive cognate interactions and effective antigen-specific antibody responses—is limited in current humanized mouse models. We therefore propose a spatiotemporal framework for the design, evaluation, and fit-for-purpose application of next-generation humanized mouse models.

Abstract: Dengue virus (DENV) causes the most prevalent arboviral infection worldwide. Alt-hough classically regarded as an acute illness, growing evidence describes Post-Dengue Syndrome (PDS) as a chronic entity with profound sequelae. This narrative review an-alyzes its pathophysiology: the cytokine storm, antibody-dependent enhancement, and NS1-triggered molecular mimicry, together with the cells that execute them—dendritic cells, mononuclear phagocytes, NK cells, platelets, and complement on the innate side; plasmablast expansion, follicular helper T cell activation, defective regulatory control, and PD-L1/PD-1-mediated exhaustion on the adaptive side. Genetic susceptibility is examined through polymorphisms of HLA, FcγRIIa, Toll-like receptor, and cytokine genes. Multisystemic manifestations are described—persistent fatigue, fibromyal-gia-like myalgia and arthralgia, alopecia, brain fog, and mood disturbance—alongside neurological complications, categorized into direct neuroinvasion and post-infectious immune-mediated damage such as Guillain-Barré syndrome and encephalomyelitis. Recent population-based data linking dengue to acute neurological events and to later cognitive decline are examined critically, as is the unsettled question of whether post-dengue neuroinflammation amounts to neurodegeneration. Finally, the influence of age and sex is addressed, and therapeutic and research priorities are outlined, of-fering an immunoclinical perspective for the multidisciplinary management of these patients.

Abstract: Background: Autoimmune outcomes following Covid-19 vaccination have been reported across the biomedical literature, yet their interpretation remains contested. While biological mechanisms linking vaccination to autoimmune outcomes have been proposed, little attention has been paid to how these mechanisms are incorporated into authors’ conclusions. Methods: This study reports Phase 1 of a two-phase qualitative, document-based analysis of interpretive practices in the biomedical literature on Covid-19 vaccination and autoimmune disorders. The analytic corpus was drawn from a published scoping review of 109 peer-reviewed studies and was limited to articles explicitly reporting biological mechanisms of action linking vaccination to autoimmune outcomes. Articles were qualitatively coded to assess alignment between reported mechanisms, contextual elements, causal language, and authors’ conclusions. Results: Of the 109 articles included in the scoping review, 52 (47.7%) reported biological mechanisms of action and were coded in Phase 1 of the study. A small number of articles (6/52, 11.5%) were coded as Consistent because they treated proposed mechanisms as causally relevant to the observed post-vaccination adverse events, although none translated this interpretation into modified vaccination recommendations. Seven articles (7/52, 13.5%) were classified as Ambiguous because they acknowledged mechanistic plausibility but left conclusions indeterminate. Most articles (39/52, 75.0%) were classified as Inconsistent because their conclusions neutralized mechanistic evidence through discursive or argumentative strategies, including hedging, narrative distancing, emphasis on methodological limitations, or competing explanations such as hypothesized genetic predisposition. Conclusion: Our analysis indicates that, within the Covid-19 vaccine–autoimmunity literature, the dominant interpretive practice is not the absence of mechanistic evidence, but the weakening or neutralization of its causal and clinical significance in authors’ conclusions. This finding underscores the importance of examining interpretive consistency alongside empirical reporting in vaccine safety research.

Abstract: Equine asthma is a chronic neutrophilic airway disease that can be exacerbated by obesity, an immunometabolic condition increasingly linked to activation of the NLRP3 inflammasome and the release of interleukin-1 beta (IL-1β). Tamoxifen, a selective oestrogen receptor modulator with immunomodulatory properties independent of its hormonal action, has previously been shown to reduce neutrophilic airway inflammation in horses, although its effect on NLRP3 inflammasome activation remains unknown. This study aimed to determine whether tamoxifen modulates NLRP3, ASC and caspase-1 gene expression, and IL-1β production, in neutrophils isolated from obese and non-obese asthmatic horses in clinical remission (n = 3 per group), using an in vitro model of inflammasome activation induced with lipopolysaccharide (LPS) and nigericin. Gene expression was assessed by RT-qPCR and IL-1β secretion by ELISA. LPS–nigericin stimulation markedly increased NLRP3 and IL-1β expression in both groups; co-treatment with tamoxifen (5 µM) significantly attenuated the LPS–nigericin-induced increase in NLRP3 expression irrespective of body condition, without affecting ASC or caspase-1. By contrast, tamoxifen significantly reduced IL-1β gene expression and secretion specifically in neutrophils from obese horses, whereas non-obese horses showed little or no response. Obese horses also exhibited higher basal IL-1β gene expression and serum concentrations than non-obese horses. These findings indicate that tamoxifen modulates NLRP3 inflammasome activation and that its effect on IL-1β is body condition-dependent, supporting its potential as an immunomodulatory agent for neutrophilic, obesity-associated equine asthma.

Abstract: Autoimmune diseases (AIDs) are a group of disorders caused by immune system dysfunction, in which the immune system mistakenly recognizes and attacks normal tissues and organs of the body. However, no radical cure is available for AIDs. Plant-derived exosome-like nanoparticles (PELNs) are nanoscale membrane structures secreted by plant cells. Recent studies have demonstrated their potential to restore immune homeostasis and retard the progression of AIDs, although the underlying mechanisms remain to be fully elucidated. This review systematically summarizes the biogenesis and functional advantages conferred by the unique composition of PELNs, with a focus on their targeting delivery potential and biological mechanisms in the treatment of various AIDs. Additionally, recent advances in the engineering modification of PELNs are discussed. This article aims to provide a theoretical basis and reference for the development of novel clinical therapeutic strategies for AIDs.

Abstract:

Background/Objectives: Therapeutic cancer vaccines can generate measurable immunity without tumor regression. Adjuvants initiate innate activation, but antitumor efficacy also requires antigen presentation, lymphoid priming, effector differentiation, tumor trafficking, cancer-cell recognition and killing, and persistence. We compared the magnitude, duration, and downstream breadth of clinically used adjuvant responses with live vaccination. Methods: We reanalyzed transcriptomic data from six randomized human vaccine studies and one controlled mouse experiment; one human study sequenced six sorted leukocyte populations. Twenty-three prespecified gene sets spanning innate ignition, antigen presentation, adaptive differentiation, trafficking, and effector programs were scored by participant-paired, baseline-adjusted comparisons with matched controls. One trial sampled placebo, adjuvanted, unadjuvanted, and live attenuated vaccines daily. Results: AS01B, AS01E, AS03, and MF59 increased type I interferon by 9.6, 8.6, 7.5, and 3.2 percentile points at 24 hours; AS04 and aluminum salt remained at control levels. Yellow fever 17D sustained interferon through day 7; MF59 resolved by day 3 and AS01/AS03 by day 7. Antigen-presenting-cell activation and MHC class I machinery rose with interferon. Apart from a small day-7 germinal-center/plasmablast signal in two AS03 trials, no reproducible sustained downstream program was detected in blood; acute cytotoxic and natural-killer-cell decreases mainly reflected blood-cell composition. Conclusions: Adjuvants produce robust ignition, but these blood datasets do not establish the later cellular functions required for tumor-cell killing. Duration is one candidate determinant of this transition. Cancer-vaccine trials should measure ignition together with compartment-appropriate priming, trafficking, cytotoxic function, and persistence across repeated doses.

Abstract: Background: Sequential cytokine conditioning of human peripheral blood mononuclear cell (PBMC)-derived cultures can generate heterogeneous extracellular outputs whose biological identity is easily oversimplified. Methods: We retrospectively integrated archived records from an IL-4/GM-CSF-supported differentiation sequence, subsequent IL-10/TGF-β1 conditioning, and recovery of a multicomponent extracellular preparation. Each analytical domain retained its documented experimental unit and was linked within a source-to-output framework. Results: One represented Annexin V/7-AAD output comprised 26,071 events with 99.66% viability. Archived cell-associated regions were integrated descriptively. The recovered preparation showed a heterogeneous particle-associated signal predominantly at approximately 170–240 nm together with reported detection of CD9, CD63, CD81, and TSG101. An aggregate summary of ten conditioned cultures reported mean extracellular values of 25,320.16 pg/mL IL-10, 659.35 pg/mL IL-4, 99.61 pg/mL IL-6, and 3.01 pg/mL TNF-α; IL-10 and IL-4 were conditioning inputs and were therefore interpreted as final-environment attributes. Conclusions: The study establishes a traceable source-to-output framework for a human PBMC-derived multicomponent extracellular preparation, preserves a biogenesis-neutral identity for its vesicular and non-vesicular components, and provides a transferable evidence-to-claim pathway for tolerance-oriented biologic development.

Abstract: Ragweed (Ambrosia artemisiifolia) pollen allergy is a major and growing public health problem worldwide, with clinical manifestations ranging from rhinitis and conjunctivitis to asthmatic episodes and anaphylaxis. The major ragweed allergen, Amb a 1, exhibits high IgE-binding potential and triggers type 1 hypersensitivity reactions. Although allergen-specific immunotherapy (AIT) effectively induces long-term immune tolerance, conventional extract-based formulations face critical limitations including batch-to-batch variability, heterogeneous allergen composition, IgE-mediated adverse reactions, inconsistent immunogenicity, and poor patient compliance. This critical re-view synthesizes and evaluates published evidence on current synthetic vaccine strategies for ragweed AIT, with emphasis on their design, immunological performance, and quality control considerations. This review critically evaluates current approaches to synthetic vaccine development for ragweed AIT, with particular focus on pep-tide-based constructs, recombinant proteins, DNA vaccines, and adjuvant-enhanced formulations, alongside corresponding quality control strategies. The available evidence indicates that synthetic vaccines provide a more rational, molecularly characterized trajectory for producing optimized AIT products with improved safety profiles, enhanced clinical efficacy, reduced injection frequency, and improved batch standardization relative to extract-based immunotherapy. These advances highlight the potential of synthetic vaccine platforms to support personalized immunotherapy and more effective disease-modifying treatment of allergic disorders.

Abstract: The G protein-coupled seven-transmembrane receptor, CXC chemokine receptor 5 (CXCR5), is predominantly expressed on B cells located in the secondary lymphoid tissues, follicular helper T cells, and lymphoma cells. Binding to its ligand, CXCL13, mediates cell migration and regulates lymphocyte trafficking. Aberrant CXCL13/CXCR5 expression and signaling have been implicated in tumor progression, autoimmune diseases, and chronic inflammatory disorders. Therefore, specific mAbs against CXCR5 are expected to be useful for diagnosis and therapeutic applications. In this study, novel anti-human CXCR5 mAbs (Cx₅Mabs) were developed through flow cytometry-based high-throughput screening. One clone, Cx₅Mab-6 (IgG_2b, κ), recognized CXCR5-overexpressed Chinese hamster ovary (CHO)-K1 cells but did not react with the other 5 CXCR receptors-overexpressed CHO-K1 cells in flow cytometry. Additionally, Cx5Mab-6 recognized endogenous CXCR5 in the human Burkitt lymphoma Raji cell line. The dissociation constant (K_D) values of Cx₅Mab-6 for CHO/CXCR5 and Raji were 3.4 × 10⁻⁹ M and 1.2 × 10⁻10 M, respectively. Furthermore, Cx₅Mab-6 is useful for Western blotting and can detect CXCR5 in human lymphoma tissue by immunohistochemistry. These findings suggest that Cx₅Mab-6 is versatile for basic research and has potential applications in clinical diagnosis.

Abstract: Entry of SARS-CoV-2 via mucosal surfaces of the upper respiratory tract including the oral cavity may be influenced by innate and adaptive immunity. We aim to determine whether antibodies in secretions might influence the SARS-CoV-2 burden and thus the severity of infection. Blood and stimulated oral fluid (SOF) samples were collected at recruitment (d0) from 173 patients, and sequentially at d14, d30 and d90 from 52 SARS-CoV-2 RT-PCR-confirmed patients. Anti-SARS-CoV-2 spike antibodies of IgG, IgA and SIgA isotypes were detected by ELISA. SARS-CoV-2 RNA copies were quantified by RT-PCR. SARS-CoV-2 RNA copies become negative by d14 in most subjects. At d14, 5/18 SOF samples continued to be RT-PCR positive. Serum/SOF IgG antibodies were detected in all patients; IgG/IgA/SIgA antibodies increased by d14 and decreased by d90. At d0 and d14, SOF RNA copies were negatively correlated with SOF/serum IgG and with SOF IgA/SIgA antibodies. Higher SOF antibodies were significantly associated with a more rapid decline in SARS-CoV-2 burden. SARS-CoV-2 RNA copies and spike-specific antibodies show differential trends during the major and minor COVID-19 waves in India. Avidity indices for SOF IgG/IgA antibodies declined by d90. Taken together our data suggests a potential functional role for SOF anti-SARS-CoV-2 spike antibodies in reducing the SARS-CoV-2 burden.

Abstract: Background/Objectives: Placebo responses can substantially influence patient-reported outcomes in clinical trials and are particularly relevant in allergen immunotherapy (AIT), where treatment efficacy is commonly assessed using symptom- and medication-based endpoints. We conducted an exploratory post hoc cross-study comparison of birch pollen-allergic participants who received pre-seasonal placebo injections in two randomised, double-blind, placebo-controlled AIT trials with participants from a third trial in whom the planned study injections were not administered before the corresponding birch pollen season. Methods: Data were pooled from three prospective clinical studies evaluating the mannan-conjugated birch pollen allergoid EP-088-T502: T502-SIT-020, T502-SIT-045, and T502-SIT-068. Placebo-injection cohorts from studies T502-SIT-020 and T502-SIT-045 were compared with the injection-free cohort from study T502-SIT-068. Clinical outcomes included the Combined Symptom and Medication Score (CSMS), daily Symptom Score (dSS), and daily Medication Score (dMS). Results: The three comparison cohorts comprised 321 participants: 161 in the injection-free cohort and 160 in the placebo-injection cohorts. Participants in the injection-free cohort had significantly higher symptom and medication scores during the secondary fixed 1–30 April analysis period than participants in the placebo-injection cohorts. Median CSMS was 1.97 in the injection-free cohort compared with 1.32 and 0.86 in the placebo-injection cohorts. Likewise, median dSS (1.08 vs. 0.79 and 0.59) and dMS (0.87 vs. 0.33 and 0.25) were higher in the injection-free cohort. Pairwise comparisons indicated statistically significant between-cohort differences. Conclusions: In this non-randomised, non-concurrent cross-study comparison, symptom and rescue-medication scores were lower in the placebo-injection cohorts than in the injection-free cohort. Because the cohorts were derived from separate studies conducted in different years, these findings are hypothesis-generating and do not establish a causal effect of placebo injections. Trial-related contextual factors and other cross-study differences should be considered when interpreting the results.

Abstract: Type 1 Diabetes Mellitus (T1DM) is preceded by a prolonged asymptomatic autoimmune phase during which islet autoantibodies represent the earliest detectable biomarkers of disease. Although radiobinding assays (RBA) remain the reference method for autoantibody detection, their use is limited by the requirement of radioactive reagents, specialized facilities and high operational costs, highlighting the need for sensitive, non-radiometric assays suitable for large-scale screening. In this study, we developed a bridge Fluorophore-Linked Immunosorbent Assay (b-FLIA) for the simultaneous detection of glutamic acid decarboxylase autoantibodies (GADA) and zinc transporter 8 autoantibodies (ZnT8A) using a recombinant ZnT8/GAD65 chimeric antigen expressed in a baculovirus–insect cell system. Assay performance was evaluated using sera from healthy controls and diabetic patients previously characterized by RBA. The b-FLIA achieved an area under the receiver operating characteristic curve of 0.9867, with 90.5% sensitivity and 100% specificity for the detection of ZnT8A and/or GADA. Furthermore, the assay showed an almost perfect agreement with RBA (κ = 0.912). These findings demonstrate that the combination of a baculovirus-expressed ZnT8/GAD65 chimeric antigen with a bridge fluorescence immunoassay constitutes a practical and sensitive platform for multiplex detection of diabetes-associated autoantibodies, with potential application in routine laboratories and future population-based screening programs.

Abstract: Background: Pharmacist involvement in immunization has expanded as a strategy to improve access to vaccines. In Costa Rica, private community pharmacies operate under a regulatory framework for vaccination services, yet little evidence exists on the private dispensing of administrable vaccines. The aim of this study was to describe the dispensing activity of administrable vaccines in private community pharmacies in Costa Rica by units, economic value, vaccine category and provincial distribution during MAT February 2025–MAT February 2026. Methods: A descriptive, retrospective, national study was conducted using an aggregated secondary IQVIA database of the Costa Rican private pharmaceutical market. Dispensed units, economic value in USD, percentage growth and share by vaccine category and province were analyzed; no individual patient, professional, establishment or nominal records were used. Results: Dispensed units rose from 162,664 to 217,387 (+33.6%). Economic value increased from USD 8,700,809 to USD 13,416,717 (+54.2%). Influenza was the highest-volume category in MAT February 2026 (87,064 units). Yellow fever showed the greatest growth, rising from 22,281 to 70,133 units and from USD 2.7 million to USD 7.0 million. HPV ranked second in economic value (USD 3.6 million). San José concentrated 63.0% of units and 52.9% of national economic value. Conclusions: The private market for administrable vaccines in Costa Rican community pharmacies expanded substantially in volume and economic value, driven mainly by yellow fever, while influenza led in units and HPV retained a major economic weight. These findings position private pharmacies as an active vaccine dispensing channel but do not allow estimation of vaccination coverage or doses actually administered.

Abstract: Encapsulating protein subunit vaccines in biodegradable microparticles (MP) can increase induction of long-term protective mucosal and systemic antibodies after respiratory administration but requires incorporation of a mucosal immunostimulant. We previously found that incorporating complement peptide-derived immunostimulant-02 (CPDI-02) with MP-encapsulated LPS-free OVA through surface modification of the same ~1 µm PLGA 50:50 MP greatly increases mucosal and systemic OVA-specific antibodies in young, naïve female C57BL/6 mice at 14 and 90 days post-intranasal administration. Here, we directly compared effects of incorporating CPDI-02 or inactive scCPDI-02 with MP-encapsulated LPS-free OVA by separate encapsulation (SE), co-encapsulation (CE), or surface modification (SM) on induction of OVA-specific IgA, IgM, and IgG antibody secreting cells (ASCs) in the lungs and spleen, IgA antibodies in nasal lavage fluid, IgA and IgG antibodies in bronchoalveolar lavage fluid, and IgG subclasses in the serum at 14 days post-intranasal administration. We found that SE incorporation induced greater or similar levels of mucosal and systemic OVA-specific ASCs and mucosal IgA and IgG titers but greater titers of systemic IgG subclasses than CE or SM incorporation versus inactive scCPDI-02. Thus, given that surface modification with CPDI-02 induces high titers of OVA-specific systemic and mucosal antibodies at 14 and 90 days post-intranasal immunization under the same experimental conditions, separate encapsulation of CPDI-02 is expected to more broadly induce long-term mucosal and systemic antibodies against MP-encapsulated protein vaccines than co-encapsulation and surface modification after intranasal and possibly other routes of mucosal immunization.