Search Results (8,866)

Background/Objectives: Following the COVID-19 pandemic, pertussis resurged sharply across Europe, with 209,674 cases reported in the EU/EEA in 2024. This study characterises the epidemiology of the 2024 pertussis resurgence across five counties of southeastern Romania, with emphasis on vaccination status, clinical severity, and regional surveillance performance. Methods: A retrospective, population-based analysis was conducted on 452 cases notified between February 2024 and January 2025, extracted from the national surveillance database. A pre-specified reclassification of PCR-positive cases yielded 326 confirmed cases. Categorical, non-parametric, correlation, and multivariate logistic regression analyses were performed. Results: The epidemic peaked in September 2024, with 56.0% of cases occurring between August and October. Children under five years accounted for 63.2% of confirmed cases, and 72.1% were not vaccinated according to age-appropriate schedule, predominantly due to parental refusal (43.0%) and non-attendance (36.6%). Pneumonia affected 36.8% of confirmed cases, ranging from 81.0% in infants under two months to 0% in adolescents. Age-appropriate vaccination was independently protective against pneumonia (adjusted OR = 0.53, 95% CI 0.29 to 0.96, p = 0.035; population attributable risk 37.3%). Significant inter-county heterogeneity was identified in PCR implementation (72 to 100%) and reporting delays. Conclusions: Vaccination gaps were the principal modifiable driver of the resurgence, supporting targeted coverage improvement and the introduction of a national maternal Tdap programme. Full article

Since 2020, recurrent waves of SARS-CoV-2 infection have persisted globally. Despite the advancements in vaccines and pharmacological treatments, a subset of patients still exhibits an aggressive form of COVID-19 requiring prolonged stays in the intensive care unit (ICU) or experiences major acute infections (or reinfections) and long-term symptoms. Endothelial dysfunction is one of the key events contributing to both the severity of acute COVID-19 and the development of long COVID (LC)/post-acute sequelae of SARS-CoV-2 infection (PASC) syndrome. Since the beginning of the pandemic, the efficacy of nutraceuticals, particularly essential micronutrients, has been investigated as a complementary treatment to prevent disease onset and improve clinical outcomes. One such bioactive molecule is folate (vitamin B9), a member of the B-vitamin family involved in the pathogenesis of multiple diseases, including viral infections and vascular disorders. This review examines the role of folic acid in COVID-19 and its interaction with homocysteine metabolism, which is frequently dysregulated in inflammatory endothelial diseases. It further discusses the potential benefits of folic acid supplementation for the prevention and treatment of COVID-19 in both the acute and long-term phases of the disease, alongside the therapeutic role of vitamin B12 supplementation in LC syndrome. Full article

Background/Objectives: Ebola Virus Disease (EVD) remains a public health threat in sub-Saharan Africa. The 10th Ebola outbreak in the Democratic Republic of the Congo (DRC) in 2018–2020 led the Rwanda Ministry of Health to launch a large-scale Ebola vaccination campaign using the two-dose Ad26.ZEBOV and MVA-BN-Filo regimen. The campaign was implemented by local organizations, the Center for Family Health Research and Rinda Ubuzima, in partnership with the Rwanda Biomedical Center. Methods: The campaign targeted those who live near or routinely cross the Rwanda/DRC border and unvaccinated first responders. Children <2 years and pregnant women were excluded. Results: Between December 2019 and September 2021, 219,775 individuals attended vaccination sites and 216,108 received the first dose. Of those, 110,699 (51.2%) were adults (≥18 years) and 105,409 (48.8%) were children aged 2–17 years. A total of 118,048 (54.6%) were women and 98,060 (45.4%) were men. Of all first-dose clients, 203,303 (94.1%) received the second dose. Participants who were older, male, in Rubavu district, and urban were more likely (p < 0.05) to be lost between the first and second dose. Most individuals who were ineligible for the second dose were women who fell pregnant after the first dose. Conclusions: Findings highlight that a large-scale vaccination campaign, including remote areas, is feasible with high adherence despite the concurrent COVID-19 pandemic. Early stakeholder engagement and local leadership were critical to success. Future studies of reasons for non-adherence, as well as strategies to integrate family planning into campaign activities to reduce ineligibility due to pregnancy, are warranted. Full article

Background. Hispanic populations in the United States experienced disproportionate health and economic impacts during the COVID-19 pandemic. This study assessed relationships between social determinants of health (SDOH) and COVID-19-related health and economic outcomes among Hispanic and non-Hispanic participants in the All of Us Research Program. Methods. Descriptive analyses and logistic regression models explored associations between all variables. Iterative proportional fitting (raking) was used to align survey samples with known population margins. Results. Hispanics reported worse outcomes across all COVID-19-related variables: lower vaccination rates and higher rates of COVID-19 symptoms and experiencing hardships due to COVID-19. Final post-raking models found Hispanics had greater odds of experiencing hardships (OR = 1.81, 95% CI = 1.55, 2.11) especially among those reporting COVID-19 symptoms (OR = 2.45, 95% CI = 1.51, 3.97). The final model identified increased rates of COVID-19 vaccination among Hispanics when controlling for gender, age, and SDOH (OR = 1.22, CI = 1.09, 1.37) than have been reported nationally during the examined time period for Hispanics. Conclusions. Uptake of COVID-19 vaccination and disproportionate negative health, economic, and social impacts of COVID-19 experienced by Hispanic communities were driven by SDOH. Findings underscore the need for targeted efforts to address SDOH to achieve the best health outcomes for all. Full article

Background: Influenza remains a major global public health threat, and vaccination is one of the most effective preventive measures. However, frequent antigenic drift and occasional antigenic shift, along with the lead time required for vaccine development and regional differences in the evolution of circulating strains, may lead to mismatches between WHO-recommended vaccine strains and circulating viruses. In addition, antiviral resistance further complicates precise influenza prevention and control. Objectives: This study aimed to evaluate the concordance of vaccine strains with circulating influenza viruses and the emergence of neuraminidase inhibitor (NAI) resistance in China. Methods: Data on antigenic characterization and antiviral susceptibility testing were extracted from weekly influenza surveillance reports published by the Chinese National Influenza Center from 2015 to 2025. Viral evolution, substitutions at key antigenic sites, and resistance-associated mutations were further examined based on sequences of circulating influenza viruses in China. Results: The overall vaccine match rates were 95.72% (95% CI: 94.02–97.43%) for A(H1N1)pdm09, 58.96% (95% CI: 54.93–62.96%) for A(H3N2), 64.45% (95% CI: 59.49–69.41%) for B/Victoria, and 95.19% (95% CI: 91.32–99.05%) for B/Yamagata in China during the 2015–2025 influenza seasons, with marked year-to-year fluctuations observed particularly for A(H3N2) and B/Victoria. The vaccine matching for cell-based A(H3N2) (70.41%, 95% CI: 65.04–75.77%) vaccine reference strains was significantly higher than that for egg-based A(H3N2) (48.09%, 95% CI: 42.63–53.55%) vaccine reference strains. Sequence analysis indicated that circulating A(H3N2) viruses showed the greatest genetic divergence from the matched egg-based vaccine strains (2.71%, 95% CI: 2.66–2.75%). Phenotypic NAI resistance was detected only in A(H1N1)pdm09 viruses, with resistance rates of 0.18% (95% CI: 0.07–0.45%) in 2023, 3.47% (95% CI: 2.63–4.57%) in 2024, and 3.01% (95% CI: 2.46–3.68%) in 2025. Neuraminidase (NA) sequence analysis showed that the key NAI resistance-associated substitution H274Y has been detected in A(H1N1)pdm09 viruses since 2015, at relatively high frequencies observed during 2015–2018. The mutation re-emerged in 2023 and presented increase trends thereafter, although no A(H1N1) pdm09 circulated during the COVID-19 pandemic. Conclusions: Antigenic concordance between vaccine strains and circulating A(H3N2) or B/Victoria viruses showed marked year-to-year fluctuations in China. Cell-based A(H3N2) vaccine reference strains showed higher antigenic concordance than egg-based strains, supporting further consideration of vaccine production platforms in A(H3N2)-predominant seasons. Phenotypic NAI resistance in circulating A(H1N1)pdm09 viruses was detected from 2023 onward in China, whereas resistance-associated NA substitutions had been detected earlier at the sequence level. Full article

Background/Objectives: People with diabetes are more susceptible to viral respiratory infections and worse clinical outcomes related to COVID-19 and influenza. Vaccination is considered an important prevention strategy. This study aimed to analyze the vaccination status against COVID-19 and influenza among people with diabetes mellitus and associated factors. Methods: An analytical cross-sectional study was conducted between May 2024 and May 2025 in 42 Primary Health Care Units in a municipality in Minas Gerais, Brazil. A total of 316 individuals with type 1 or type 2 diabetes mellitus participated in the study. Data were collected using a structured instrument containing socioeconomic, cultural, behavioral, and clinical variables, in addition to verification of vaccination records through physical vaccination cards and information systems. Descriptive analyses and logistic regression models were performed to estimate crude and adjusted odds ratios, with respective 95% confidence intervals. Analyses were performed using Statistical Package for the Social Sciences and Stata. Results: Adherence to COVID-19 vaccination was 21.5%, whereas influenza vaccination adherence reached 85.4%. In the multivariable analysis of COVID-19 vaccination status, previous influenza vaccination (OR = 7.74; 95% CI: 1.81–33.2) and alcohol consumption (OR = 2.11; 95% CI: 1.13–3.89) were positively associated with vaccination. Conversely, access to social media or other communication channels (OR = 0.47; 95% CI: 0.24–0.92) and insulin use (OR = 0.42; 95% CI: 0.21–0.84) were associated with lower odds of COVID-19 vaccination. Regarding influenza vaccination, positive associations were identified for religious affiliation (OR = 6.46; 95% CI: 1.79–23.30), previous COVID-19 vaccination (OR = 10.2; 95% CI: 2.22–47.06), and longer duration of diabetes diagnosis (OR = 3.47; 95% CI: 1.32–9.20). In contrast, alcohol consumption (OR = 0.42; 95% CI: 0.21–0.86), insulin use (OR = 0.35; 95% CI: 0.16–0.76), and absence of medical follow-up (OR = 0.34; 95% CI: 0.13–0.85) were associated with lower odds of influenza vaccination. Conclusions: The findings revealed a heterogeneous vaccination pattern among individuals with diabetes mellitus, in which higher influenza vaccination coverage contrasted with low adherence to COVID-19 vaccination, reflecting not only differences in the historical consolidation of immunization strategies but also contemporary dynamics related to risk perception, trust, and information circulation. The strong association with previous vaccination history suggests that vaccine adherence is part of a continuum of preventive behaviors mediated by the relationship with healthcare services and by the internalization of healthcare practices over time. Full article

Background: The COVID-19 pandemic exposed critical gaps in pandemic preparedness and highlighted the need for vaccine platforms capable of rapid adaptation. Outer membrane vesicle (OMV)-based platforms utilizing vesicles derived from genetically detoxified Neisseria meningitidis serogroup B (Nm-nOMV) represent a promising plug-and-play approach. Methods: This Phase I, first-in-human, randomized, double-blind, placebo- and OMV-controlled trial, evaluated safety, tolerability, and immunogenicity of intranasally administered OMVs combined with SARS-CoV-2 Spike protein in healthy SARS-CoV-2 seropositive adults aged 18–55 years. Forty participants were enrolled across two cohorts: a low-dose cohort receiving 140 μg OMV/70 μg Spike (OMV + Spike, n = 13; OMV alone, n= 3; Placebo, n = 5) and a high-dose cohort receiving 280 μg of OMV/140 μg of Spike (OMV + Spike, n = 13; OMV alone, n = 3; Placebo, n = 3), administered on Days 1 and 22. Safety was assessed through adverse events, vital signs, laboratory parameters, ECG, and pulse oximetry. Immunogenicity was evaluated via systemic SARS-CoV-2 neutralizing antibodies, antigen-specific antibodies (IgG and IgA), and mucosal antibodies (IgA in nasal wash). Results: Intranasal administration of OMVs combined with SARS-CoV-2 Spike protein was safe, well-tolerated, and immunogenic. No serious adverse events were reported, and adverse events were predominantly mild and transient. Dose-dependent increases in systemic and mucosal immune responses were observed, with statistically significant enhanced serum IgG and nasal wash IgA antibodies in the high-dose group. Conclusions: The current clinical data confirm key aspects of the preclinical profile, which demonstrate the potential of the Nm-nOMV platform as a strong adjuvant for mucosal vaccines. These findings support the broader application of the Nm-nOMV vaccine platform in pandemic preparedness. Full article

This review describes a novel method for increasing the effectiveness of inactivated enveloped whole-virus vaccines by targeting them for extensive uptake by antigen-presenting cells (APCs). Several inactivated whole-virus vaccines with dense glycan shields display suboptimal effectiveness because the multiple carbohydrate chains (glycans) on the virus mask immunogenic peptides and surround the virus with a negative electrostatic charge that decreases uptake by APCs. It is postulated that engineering such vaccinating viruses to present the carbohydrate antigen “α-gal epitope” on the glycan shields will immunocomplex them with the anti-Gal antibody; thus, it will target them for robust uptake by APCs. Anti-Gal is an abundant natural antibody in humans, constituting ~1% of human circulating immunoglobulins. The ligand of anti-Gal is the α-gal epitope, which is naturally synthesized in non-primate mammals and New World monkeys by the glycosylation enzyme α1,3galactosyltransferase. This enzyme is encoded by the GGTA1-gene. Viral vaccines presenting multiple α-gal epitopes on their glycan shield bind anti-Gal and activate the complement system to produce complement chemotactic cleavage peptides C5a and C3a that induce extensive recruitment of APCs to vaccine injection sites. The virion-bound anti-Gal further targets the viral vaccine for robust uptake by APCs, following binding of its Fc “tail” to Fcγ-receptors on APCs. The efficacy of this method was studied in anti-Gal-producing mice with α-gal presenting inactivated influenza virus vaccine and with gp120 of HIV presenting this epitope. These studies indicated that virus vaccines engineered to present α-gal epitopes increase anti-virus antibody production and virus-specific T-cell activation by 15- to 100-fold in comparison to the same vaccines lacking α-gal epitopes. It is suggested that α-gal presenting inactivated SARS-CoV-2 virus vaccines can induce a similar protective long-term immune memory against S- M-, E-, and N-viral proteins. Furthermore, immune-escaping variants of the mutated S-protein may be destroyed by antibodies to M and E proteins, and cells infected with such variants may be killed by cytotoxic T cells specific to peptides of the N-protein. Such an anti-M-, E-, and N-protein immune protection may prevent expansion of these variants and thus may avoid the need for immunization with COVID-19 vaccines every 6 months or following the appearance of new variants. A similar potent immunization may be achieved with an inactivated Ebolavirus vaccine engineered to present α-gal epitopes on the glycan shield. The resulting immune response to the various Ebolavirus proteins also may contribute to cross-reactive protection against other Ebolavirus species containing proteins with evolutionarily conserved structures. An effective method for the preparation of a whole-virus vaccine presenting α-gal epitopes is by arming it with the GGTA1-gene inserted into the viral genome. Such virions will present multiple α-gal epitopes on their glycan shield, which will amplify their immunogenicity instead of reducing it in the wild-type virus. Full article

Background: While vaccines are designed to elicit targeted immune responses, in some cases, the immunogenic molecules employed can inherently interact with broader host cellular pathways as a secondary consequence. This phenomenon can be exemplified by COVID-19 vaccines. COVID-19 vaccines, including mRNA platforms, use the SARS-CoV-2 spike protein as an immunogen to induce the production of neutralizing antibodies. The spike protein binds the ACE2 (angiotensin-converting enzyme 2) receptor on human cells, mediating viral entry and infection. ACE2 is widely expressed across multiple tissues and is a key component of the renin–angiotensin–aldosterone system (RAAS) that acts as a homeostatic regulator of systemic and local blood flow, blood pressure, cardiac function, fluid balance and immunity. Some studies have proposed the interaction between the spike protein and ACE2 as a possible contributing factor to rare adverse effects observed following COVID-19 vaccination, including myocarditis, pericarditis, thrombosis, and reported alterations in blood pressure, though these mechanisms remain to be fully elucidated. Objectives: As a proof-of-concept approach in vaccine antigen development, we engineered SARS-CoV-2 spike mutants with impaired binding to the host receptor ACE2. Methods: By rational design, we produced and validated in vitro and in vivo spike point mutants that do not effectively bind ACE2. Results: The engineered spike mutants do not effectively bind the human entry receptor ACE2 while retaining the immunogenic properties equal to or better than the wild type spike and thus generate a protective response in animals when used as a vaccination agent. Conclusions: By establishing a straightforward molecular strategy for rational vaccine design, this work demonstrates the feasibility of limiting specific antigen–host receptor interactions while maintaining immunogenicity. This approach may be applicable to future vaccination strategies where antigen interaction with host cells could potentially interfere with physiological pathways. Full article

Neutralizing antibodies (NABs) play a critical role in assessing the immune response elicited by vaccines, providing insight into their protective efficacy. Despite their importance, there is a notable gap in research directly comparing NAB levels among individuals vaccinated with different vaccines, across diverse ethnicities, and between genders. The study aimed to compare NAB levels across variables such as vaccination status, vaccine type, age, gender, and ethnicity. The NAB levels among different study groups were measured using the Finecare RBD Antibody Test and the cPass kit (ELISA). The data was analyzed statistically using SPSS version 27. A total of 172 study subjects were analyzed. The mean age of participants was 45.03 ± 16.72 years, with 50.9% male and 77.3% of Malay ethnicity. Median NAB levels, assessed by both assays, were highest in females, vaccinated healthy participants, and those who received the Pfizer vaccine. Age-group comparisons revealed variations in median NAB levels across studied groups. Participants aged 10–25 years in the vaccinated healthy (VH) group exhibited the highest median antibody levels; on the other hand, the 26–45 year age group showed the highest median levels in the breakthrough infection (BI) and certain non-vaccinated categories. Ethnic group comparisons highlighted that Malays consistently had the highest median NAB levels. Significant differences in antibody levels were found across vaccination status, ethnicity, and vaccine type (p < 0.001). This study underscores the influence of vaccination status, demographic factors, and vaccine type on NAB levels. The Finecare RBD Antibody Test and cPass kit demonstrated comparable trends, highlighting their utility in evaluating vaccine-induced immunity. The findings of this study highlight the need for tailored immunization strategies to optimize protective immunity. Full article

Public health policy foundationally impacts how pathogens spread, yet despite multiple pathogens of broader societal concern emerging, little research has examined how policy affects pathogen evolution. To evaluate this connection, we examine how varying public health approaches impact how viral immune susceptibility, including resistance to vaccines, evolves. Integrating evolutionary epidemiological modeling and critical geography, we compare how distinct public health responses early in the COVID-19 pandemic affected the potential evolution of immune evasion in SARS-CoV-2 across four territories: Costa Rica, Panama, Texas, and Uruguay. We use parameter estimates inferred from confirmed case and vaccination time series via stochastic ensemble Kalman filtering in each territory. Our analyses suggest viral immune resistance was most likely to emerge in Texas, which relied almost exclusively on vaccines for disease control. In contrast, regions with comparatively fewer health disparities that also rigorously applied interventions, such as shelter-in-place orders and household support, may have better prevented vaccine resistance from evolving. These comparative analyses highlight the key role policy choices play, potentially representing different governance goals for population health and wellbeing. We argue that such choices impact not only disease spread but also pathogen evolution along epidemiologically critical dimensions like viral immune susceptibility. Our study thus demonstrates how public health priorities drive social–evolutionary feedbacks. Full article

Background: Since 2014, all Australian jurisdictions have progressively amended legislation to authorise pharmacists to administer vaccines, evolving from restricted pilots to an essential public health pillar. Objective: This review analyses the longitudinal evolution of pharmacist-administered vaccinations (PAVs), documenting changes in authorised vaccines, age eligibility, and regulatory frameworks across all Australian jurisdictions. Methods: A retrospective review of Australian jurisdictional legislation, regulations, and policy documents was undertaken. Searches included official legislative registers, Government Gazettes, Health Department protocols, and professional guidance published by Pharmaceutical Society of Australia (PSA) and The Pharmacy Guild of Australia between 2014 to 2026. Documents were independently reviewed by five authors, followed by secondary verification and consensus-based adjudication to resolve discrepancies and confirm findings. Results: PAVs scope was expanded from a single influenza pilot in 2014 to include over 21 vaccine-preventable diseases by 2026. The COVID-19 pandemic catalysed rapid reform, leading to the standardisation of age eligibility (largely ≥5 years). A landmark milestone occurred in 2025 when South Australia enabled pharmacists to administer any vaccine within their professional scope. Conclusion: Legislative reforms have significantly enhanced vaccine accessibility. However, jurisdictional fragmentation persists. National harmonisation, using a competency-based model similar to South Australia, is recommended to streamline delivery and optimise public health outcomes. Full article

Viral vaccine development requires both mechanistic understanding of protective immunity and translational study designs that connect preclinical data with human outcomes. Animal models remain important for early assessment of safety, immunogenicity and protective efficacy, but their predictive value depends on the question being asked, the pathophysiology of infection, the immune mechanisms expected to mediate protection, and the biomarkers chosen to bridge animal and human data. This review focuses on viral vaccines and examines innate and adaptive mechanisms of vaccine-induced protection, including B cell and antibody responses, Fc-mediated functions, Fc glycosylation, T cell memory and CD8+ cytotoxic responses. We discuss common reasons for clinical failure and show how preclinical endpoints can be classified as human-counterpart, surrogate or comparative/mechanistic readouts. Influenza and COVID-19 examples illustrate how different models can be combined across discovery, challenge, transmission and late-stage bridging studies. Emerging tools such as systems serology, omics, AI/ML and new approach methods can improve candidate prioritization, but their value depends on assay standardization, biological validation and cautious interpretation. A mechanism-driven model cascade, paired with human-relevant immunological readouts, can improve preclinical interpretation and reduce the risk of advancing candidates that are unlikely to succeed in clinical trials. Full article

The 2019 coronavirus disease pandemic (COVID-19) showed how genetic mutations can alter coronavirus characteristics. However, the evolution of livestock coronaviruses remains understudied. We analyzed 15 bovine coronavirus (BCoV), three porcine hemagglutinating encephalomyelitis virus (PHEV) and 18 porcine respiratory coronavirus (PRCV) isolates, mainly from Belgian livestock collected between 2020 and 2023. Spike gene phylogenetic analysis showed nucleotide substitution rates comparable between BCoV and PRCV, while PHEV appeared slower. Unlike severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), synonymous substitutions were preferred, limiting amino acid variation across decades in the animal coronaviruses. Virus neutralization assays with swine antisera indicated minimal antigenic change in PHEV and PRCV. Recent BCoV isolates showed antigenic divergence from the classical Mebus vaccine strain. The impact of this divergence on vaccine efficacy may warrant further research. Our findings underscore the need for periodic surveillance, as changes in surface proteins may affect pathogenicity, tissue tropism, host range and vaccine efficacy. Full article

The continuous evolution of the SARS-CoV-2 virus, marked by the emergence of new variants, poses a significant threat to the efficacy of existing vaccines. However, a promising approach to addressing vaccine failure caused by viral mutations (particularly in the spike protein) is the development of a variant-proof (conserved), non-spike, multiepitope universal nanostructure vaccine with multifunctionality, biocompatibility, self-adjuvanticity, and structural similarity to pathogens in terms of size and shape. This study aimed to design a self-assembled nanostructure vaccine (SANV) featuring pentameric and trimeric coiled-coil peptide motifs, as well as other functional motifs, including epitopes, TAT, PADRE, and adjuvant. The cytotoxic T lymphocyte (CTL), helper T lymphocyte (HTL), and B lymphocyte (BL) epitopes of SANV were screened from the IEDB with more than 50% individual predicted population coverage (PPC) and fused using linkers to enable self-assembly. The multimerization of the 24 SANV monomers was modeled using the GalaxyHomomer and AlphaFold web servers. Subsequently, the leading SANV constructs with (SANVa9) and without (SANVb6) adjuvant were analyzed for their physicochemical profiles and assessed for antigenicity, allergenicity, solubility, and antioxidant potential. Furthermore, the molecular interactions, specificity, and stability of SANVa9 and SANVb6 with the broadly neutralizing sarbecovirus antibody 5817 and toll-like receptors (TLR2, TLR3, and TLR7) were analyzed using molecular docking and simulation over a 100-nanosecond time scale. Finally, the comparative immune simulation profiles of SANVa9 and SANVb6 with controls indicated stronger, broad-spectrum immune responses that could be translated into in vitro and in vivo studies and warrant further evaluation before clinical use. Full article