Search Results (2,554)

Introduction: As seasonal influenza vaccination coverage among healthcare workers (HCWs) in Serbia remains suboptimal, we aimed to identify HCW beliefs associated with their intention to receive seasonal influenza vaccine (“vaccination intention”) in the season 2024/2025. Methods: In a cross-sectional survey conducted in 2024, healthcare institutions were selected from a national registry, using multi-stage sampling stratified by geographical region and healthcare level. All consenting HCWs present on the survey day self-completed questionnaires. Five dichotomised Health Belief Model constructs were assessed: perceived susceptibility to influenza, perceived disease severity, perceived vaccination benefits, perceived physical and psychological barriers, and perceived cues for action (recommendation by another HCW, someone close, or a supervisor). The association of vaccination intention (yes/no/undecided) with Health Belief Model constructs, demographic and occupational factors were assessed using multinomial logistic regression. Results: Of 1919 respondents, 30% declared positive vaccination intention, 52.5% no intention, and 17.5% were undecided. Compared with no intention, positive vaccination intention was associated with perceived self-benefit (aOR = 6.22, CI = 3.49–11.08), perceived patient benefit (aOR = 2.26, CI = 1.48–3.45), perceived susceptibility (aOR = 3.26, CI = 2.19–4.86), and perceived vaccine safety (aOR = 2.95, CI = 1.93–4.50). Participants were more likely to be undecided than reject vaccination if they experienced higher perceived susceptibility (aOR = 2.93, CI = 1.89–4.54), perceived influenza as severe (aOR = 2.04, CI = 1.30–3.21), perceived patient benefits (aOR = 1.77, CI = 1.14–2.74), or recalled receiving a recommendation from another HCW (aOR = 2.63, CI = 1.17–5.85). Conclusions: HCWs’ positive vaccination intention was associated with beliefs relevant for personal health and patient benefits. The undecided group showed a distinct pattern of beliefs warranting their separate analysis and specific approaches. Full article

Influenza A(H1N1)pdm09 remains one of the predominant seasonal influenza viruses worldwide and continues to evolve under the combined effects of host immunity, vaccination, and changing epidemiological conditions. However, the long-term impact of the COVID-19 pandemic on its evolutionary dynamics remains poorly understood. We investigated the genetic variability and phylodynamic evolution of the hemagglutinin (HA) and neuraminidase (NA) genes of Italian A(H1N1)pdm09 viruses collected between 2009 and 2026. Time-calibrated phylodynamic analyses, Bayesian Skyline Plots (BSPs), Lineages Through Time (LTT) graphs, principal component analysis (PCA), and codon-based selection analyses were used to characterize long-term evolutionary patterns. Both HA and NA followed continuous evolutionary trajectories, with a marked post-2020 genetic shift associated with the emergence of 6B.1A.5a.2-related clades. HA showed greater evolutionary variability than NA, whereas selection analyses identified only one positively selected site in HA and none in NA, consistent with reduced adaptive diversification in recent strains. Phylodynamic analyses revealed a marked decline in effective population size and lineage accumulation during the COVID-19 pandemic, followed by renewed expansion after 2022. Overall, Italian A(H1N1)pdm09 viruses exhibited reduced genetic diversity, limited evidence of positive selection, and coordinated genomic restructuring following the pandemic. These findings provide new insights into the long-term evolutionary dynamics of A(H1N1)pdm09 in Italy and reinforce the importance of sustained genomic surveillance for anticipating evolutionary changes and informing evidence-based public health strategies. Full article

Background: Young children are at high risk of influenza and its complications, yet evidence on the real-world effectiveness of egg-based inactivated influenza vaccines in children aged 6–59 months remains limited during antigenically drifted seasons. Methods: We conducted a population-based retrospective cohort study using linked immunization and influenza surveillance records from August 4, 2025 to February 8, 2026. Vaccinated and unvaccinated children aged 6–59 months were matched 1:1 using propensity scores based on demographic characteristics, routine and non-routine vaccination history, prior seasonal influenza vaccination (SIV), and prior influenza infection. For vaccinated children, the index date was defined as the date of the last SIV received during the study period; matched unvaccinated children were assigned the corresponding index date. Follow-up began 14 days later and continued until influenza onset or February 8, 2026. Adjusted vaccine effectiveness (aVE) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. Sensitivity analyses included a negative control outcome analysis using varicella infection, a multivariable logistic regression analysis with influenza infection as the outcome, and a time-dependent exposure Cox regression analysis in the full eligible cohort. Results: A total of 26,444 children were included in the final cohort (13,239 vaccinated and 13,205 unvaccinated). Influenza incidence rates were 28.70 and 40.21 per 100 person-years in vaccinated and unvaccinated groups, respectively. The aVE was 28.82% (95% CI: 23.07–34.14%). aVE was generally consistent across most subgroups, but was lower in children vaccinated in the previous season than in those without prior-season vaccination (20.41% vs. 34.28%; p for interaction = 0.016). Sensitivity analyses yielded comparable VE estimates. Conclusions: Egg-based inactivated influenza vaccination conferred moderate real-world protection against influenza in children aged 6–59 months during the 2025/26 season. Continued monitoring of vaccine effectiveness is needed to inform vaccination strategies in young children. Full article

Adult vaccination is a critical component of preventive healthcare, reducing morbidity and mortality from vaccine-preventable diseases. Despite established recommendations, adult immunisation coverage remains suboptimal, particularly for vaccines beyond influenza and COVID-19. In the United Arab Emirates (UAE), limited evidence exists regarding adult vaccine uptake and determinants influencing immunisation behaviour within its diverse population. Understanding vaccine-specific coverage and associated sociodemographic, healthcare, and workplace factors is essential to guide targeted strategies that strengthen adult immunisation. A cross-sectional study was conducted among 1330 adults aged ≥ 18 years residing in the UAE. Data were collected using a structured self- or interviewer-administered questionnaire assessing uptake of recommended adult vaccines, including COVID-19, influenza, pneumococcal, herpes zoster, Tdap, and HPV. Sociodemographic characteristics, healthcare access, insurance status, workplace factors, and perceived barriers were also assessed. Descriptive statistics summarised vaccination coverage, and associations between uptake and key determinants were examined using SPSS version 30. Statistical significance was defined as p < 0.05. Overall, 71.0% reported receiving at least one adult vaccine. Uptake was highest for COVID-19 (64.9%) and influenza (57.8%), while pneumococcal, herpes zoster, and Tdap coverage remained low (12–13%). HPV uptake was 22.6% among females and 18.9% among males. Higher uptake was observed among females and adults. Social encouragement, insurance coverage, and healthcare access were associated with vaccination, whereas lack of awareness and logistical barriers hindered uptake. Although overall uptake was moderate, significant gaps persist. Integrating vaccination into routine healthcare services and addressing structural and communication barriers are necessary to improve adult vaccination coverage. Full article

Background: Community-acquired respiratory viruses (CARVs) cause significant morbidity and mortality in patients with haematological malignancies and those undergoing haematopoietic cell transplantation (HCT). Despite this, clinical management remains variable. This study evaluated clinicians’ awareness, diagnostic practices, and treatment approaches to major respiratory viruses in this high-risk population. Methods: An international electronic survey using non-probability convenience sampling was conducted among haematology, oncology, intensive care and emergency medicine physicians. Four real-life clinical cases were converted into standardised vignettes covering human metapneumovirus (HMPV), respiratory syncytial virus (RSV), human parainfluenza virus (HPIV) and influenza A virus (IAV). The questionnaire assessed reported testing strategies and intended management, including antiviral and immunoprophylactic interventions. Responses were analysed descriptively; no inferential between-group comparisons were performed. Results: Ninety-eight clinicians from 26 countries responded. Diagnostic approaches, including testing indications and panel selection, varied among respondents. For HMPV and HPIV, respondents mainly reported supportive care, immunoglobulin replacement, and infection-control measures in the absence of established pathogen-specific interventions. RSV practice was heterogeneous: systemic ribavirin was considered by 45/96 (46.9%) respondents, including 34/96 (35.4%) when guided by an immunodeficiency score. IAV management was more consistent, with reported availability of vaccination and antiviral therapy and frequent use of post-exposure prophylaxis. Conclusions: Within this international convenience sample, clinicians reported variation in respiratory viral testing and in how results informed intended management. Because sampling was non-probability-based and respondent groups were small and unevenly distributed, the findings should not be interpreted as representative estimates of international practice. IAV testing was most consistently linked to established treatment and prevention, RSV showed greater therapeutic and preventive heterogeneity, and HMPV/HPIV testing primarily informed infection control, monitoring and antimicrobial stewardship. Full article

Background/objective: Older adults experience a disproportionate burden of severe influenza. In the P303 trial (NCT058279789), mRNA-1010 showed greater immunogenicity versus high-dose inactivated influenza vaccine (HD-IIV4) in adults ≥65 years of age. Here, we used a correlate-of-protection framework to estimate the relative VE (rVE) of mRNA-1010 compared with HD-IIV4. Methods: A sigmoidal function was used to model the relationship between geometric mean haemagglutinin assay inhibition (HAI) titers (GMTs) and vaccine efficacy (VE) using data from the P304 trial (NCT06602024), which compared mRNA-1010 and the standard-dose IIV4 in adults ≥50 years of age. The model was then applied to GMTs from the P303 trial to estimate rVE of mRNA-1010 vs. HD-IIV4 in adults ≥65 years. Temporal waning and weighting of case distributions were incorporated to provide a season-integrated estimate. Simulations were performed for three influenza seasons (A/H1N1-dominant, A/H3N2-dominant, and balanced), with a sensitivity analysis varying vaccination and epidemic peak timing. Results: At Day 29, rVE for mRNA-1010 vs. HD-IIV4 was 24.1% (95% CI: 18.2–29.5%) against A/H1N1, 14.5% (8.3–20.3%) against A/H3N2, and 21.0% (16.0–25.8%) against B/Victoria. The season-integrated rVE was 12.4% (3.4–21.3%) across all three strains, with point estimates ranging from 11.6% to 12.6%. Similar findings were seen across simulated seasons, with rVE estimates ranging from 8.8% to 14.3% when varying vaccination timing, peak timing, and strain dominance. Conclusions: Based on this CoP framework, mRNA-1010 was projected to have higher VE than HD-IIV4 in adults ≥65 years of age across a range of simulated epidemiological conditions. Full article

Neuraminidase (NA) is a major surface glycoprotein of influenza viruses that mediates the release of progeny virions from infected cells. Although both hemagglutinin (HA) and NA are targets of protective immune responses, current seasonal influenza vaccines are primarily standardized based on HA content, resulting in variable and often suboptimal induction of NA-specific immunity. Therefore, NA is subject to different immune pressures and exhibits distinct patterns of antigenic evolution. Increasing evidence suggests that neuraminidase-inhibiting (NAI) antibodies contribute to protection against influenza by limiting viral replication and reducing disease severity, particularly when HA antibodies are poorly matched to circulating strains. The recent emergence of highly pathogenic avian influenza (HPAI) H5N1 viruses with widespread transmission in dairy cattle and increasing zoonotic infections has renewed interest in understanding the extent of pre-existing human immunity to NA and its potential role in mitigating disease caused by emerging influenza viruses. However, the breadth of cross-reactive NA immunity against zoonotic influenza viruses remains incompletely understood. In this review, we summarize current knowledge of population immunity to influenza NA, with a focus on the roles of immune imprinting, natural infection, and seasonal vaccination in shaping NA-specific antibody responses. We further discuss the cross-reactivity of these antibodies against zoonotic influenza viruses and highlight the implications of NA immunity for pandemic preparedness. Full article

Background/Objectives: Humans are primarily infected by two distinct seasonal influenza A virus (IAV) subtypes, A(H1N1)pdm09 and A(H3N2). Because IAV mutates rapidly, it continuously escapes existing protective antibodies. However, repeated exposure to these evolving strains increases the diversity of virus-specific memory B cell (MBC) population. To investigate the extent of this diversity and cross-reactivity of IAV- specific immunity in adults, and its possible impact on emerging strains, we analyzed the hemagglutinin (HA)-specific MBC repertoire of an adult frequently immunized with seasonal vaccines. Methods: High-throughput single-cell sequencing of HA probe-positive MBCs collected from an individual with repeated seasonal influenza vaccination was performed. Monoclonal antibodies (mAbs) from multicell clonotypes were tested for HA binding and influenza virus neutralization. Results: Two clonotypes were identified that bound to both A(H1) and A(H3) HAs from strains circulating before and after the season of blood collection. Both clonotypes neutralized A(H3N2) strains, while one also neutralized A(H1N1)pdm09 strains. Notably, these cross-group binders showed affinity for A(H5), A(H7) and A(H9) avian influenza HAs and neutralized bovine A(H5N1) IAV. Conclusions: Our findings suggest that seasonal vaccination can support pre-existing cross-reactive B-cell immunity in some individuals. This underscores the importance of studying influenza-specific MBC repertoires across diverse populations to better understand immune dynamics and improve vaccine design. Full article

Highly pathogenic avian influenza H5N1 virus (H5N1 HPAIV) has long circulated in wild waterfowl and poultry and continues to cross species barriers, posing sustained threats to livestock productivity and public health. The 2024 outbreak of H5N1 HPAIV in dairy cattle across multiple U.S. states represents the first recognized large-scale transmission event of this virus in ruminants, reshaping our understanding of its host range and transmission ecology. This review summarizes recent advances in the epidemiology, virological characteristics, transmission, pathogenesis, surveillance, and control of dairy cattle-associated H5N1. The initial multistate outbreak was dominated by clade 2.3.4.4b genotype B3.13, whereas subsequent independent introductions of genotype D1.1 demonstrated that repeated avian-to-cattle spillover also contributes to the evolving outbreak ecology. A defining feature is efficient replication in bovine mammary epithelial cells, resulting in high viral titers in milk, supporting milk-associated exposure and milking-related contamination as plausible components of transmission, although the relative contribution of different routes remains unresolved. Infected cattle typically show reduced feed intake, a marked decline in milk production, abnormal milk, and mild systemic signs, whereas severe respiratory disease and mortality are uncommon. Mutations such as PB2-M631L, PA-K497R, and changes in NP and NS1 may promote replication and immune evasion in bovine cells, while genotype-specific PB2 adaptations highlight the potential for further mammalian adaptation. Human infections reported to date have been predominantly mild and associated with occupational exposure, with no evidence of sustained human-to-human transmission. Experimental vaccine studies have begun to demonstrate immunogenicity in cattle, although protection against mammary infection, viral shedding, and transmission remains to be established. Future priorities include clarifying mammary tropism and transmission dynamics, while strengthening diagnostics, farm biosecurity, vaccination, evaluating cattle vaccination strategies, and integrated One Health surveillance. Full article

Background/Objectives: Severe acute respiratory syndrome (SARS) remains an important cause of hospitalization and mortality, particularly among vulnerable populations. Understanding the factors associated with previous hospitalization may support more effective prevention and vaccination strategies. This study aimed to analyze the epidemiological profile of previous hospitalization among patients with SARS in the state of Pernambuco, Brazil. Methods: A quantitative, retrospective, cross-sectional study was conducted using data from the Influenza Epidemiological Surveillance System (SIVEP-Gripe), including 79,852 adult patients (≥18 years) notified with SARS in Pernambuco between 2021 and 2024. Sociodemographic, clinical, and vaccination-related variables were analyzed to identify factors associated with previous hospitalization. Results: The prevalence of previous hospital admission (readmission history) was 6.6%. Patients with previous hospitalization had a significantly higher median age compared to those without previous hospitalization (66 vs. 63 years; p < 0.001). The prevalence of previous hospitalization was higher among individuals with chronic comorbidities, particularly hematologic diseases (prevalence ratio [PR] = 1.95; 95% confidence interval [CI]: 1.51–2.51; p < 0.001) and asthma (PR = 1.67; 95% CI: 1.42–1.96; p < 0.001). Influenza vaccination was associated with a lower prevalence of previous SARS hospitalization (PR = 1.29; 95% CI: 1.03–1.61; p = 0.023). In contrast, COVID-19 vaccination status showed no significant association with previous hospitalization. A history of previous SARS hospitalization was associated with a higher prevalence of death in subsequent hospitalizations (PR = 1.09; 95% CI: 1.01–1.18; p = 0.022). Conclusions: Older adults and individuals with chronic comorbidities showed a higher prevalence of previous SARS hospitalization in Pernambuco. The findings show an association between influenza vaccination and a lower prevalence of previous SARS hospitalization and highlight the importance of post-discharge follow-up and epidemiological surveillance. Full article

Bovine adenovirus (BAdV)-based vectors, particularly those derived from bovine adenovirus 3 (BAdV-3), are emerging non-human adenoviral platforms for veterinary vaccine development. Adenoviral vectors are attractive for vaccination because they mediate efficient transgene expression, remain largely episomal, and induce robust innate and adaptive immune responses. However, widely used human adenoviral vectors, especially human adenovirus 5 (HAdV-5), may be compromised by pre-existing anti-vector immunity, supporting the development of rare human serotypes and non-human adenoviral alternatives. BAdV-3 is the best-characterized BAdV for recombinant vector engineering and has been used to express heterologous antigens from bovine herpesvirus-1, bovine respiratory syncytial virus, influenza virus, and Mycobacterium tuberculosis. Available evidence indicates that BAdV-based vectors can induce humoral, cellular, and mucosal immune responses and support intranasal antigen delivery. Protective efficacy has been demonstrated in selected experimental models, including mice and ferrets for influenza and tuberculosis vaccine candidates, whereas cattle challenge evidence remains more limited and is primarily represented by BHV-1 gD-expressing BAdV-3 vectors. These features make BAdV vectors relevant to bovine respiratory disease control, livestock vaccination, and One Health-oriented vaccine preparedness. Nevertheless, the platform remains at an early developmental stage. Key gaps include limited target-species efficacy data, pre-existing BAdV immunity in cattle, vector shedding, recombination risk, genetic stability, producer cell optimization, manufacturing scalability, and regulatory feasibility. Full article

Background/Objectives: Neurocognitive disorders represent a growing burden among older adults. Although respiratory vaccines have demonstrated efficacy and safety in preventing acute respiratory events, their potential impact on the development of chronic neurocognitive disorders, such as cognitive impairment, dementia, and Alzheimer’s disease (AD), has not been extensively explored. The objective of this scoping review was to synthesize and analyze the available evidence on the association between respiratory vaccination and the risk of developing cognitive impairment, dementia, and Alzheimer’s disease. Methods: A scoping review was conducted in accordance with the PRISMA-ScR guidelines. A literature search was performed in the PubMed, Scopus, and Web of Science databases through 15 June 2026. Studies involving older adults (≥60 years), irrespective of their baseline neurocognitive status, were included. Observational studies (cohort and case–control studies) were considered. Editorials, narrative reviews, and other non-original articles were excluded. Results: Eighteen studies were included, with cohort studies being the predominant design. Four main categories of respiratory vaccines were evaluated: influenza, COVID-19, respiratory syncytial virus (RSV), and pneumococcal vaccines, in relation to the risk of cognitive impairment, dementia, and AD. Influenza vaccination was associated with a lower risk of dementia and AD, with a potential dose–response relationship observed, whereby a greater number of vaccinations was associated with a greater reduction in risk. Pneumococcal vaccination was also associated with a lower risk of dementia and AD, particularly among individuals who received a greater number of vaccine doses. In contrast, the evidence regarding COVID-19 and RSV vaccines was limited and yielded heterogeneous findings. Conclusions: Influenza and pneumococcal vaccination maybe associated with a lower risk of Alzheimer’s disease and dementia. However, the evidence regarding COVID-19 and RSV vaccines remains limited, and additional studies are needed to clarify their impact on the risk of developing neurocognitive disorders. Full article

Background/Objectives: Particulate vaccine formulations require delivery systems and immunostimulatory components that support antigen-presenting cell interaction while maintaining formulation stability and cytocompatibility. This study examines Guanine-α-D-Fructose (GDF), a guanine–fructose small-molecule immunostimulatory candidate, incorporated into poly(lactic acid-co-glycolic acid) (PLGA) microparticles and benchmarked in vitro against established adjuvant formulations containing Alum or AddaVax. Methods: GDF-loaded microparticles were prepared and characterized for particle size, morphology, surface charge, entrapment efficiency, and release behavior. Their in vitro immunostimulatory activity was evaluated using murine dendritic cells. To explore formulation compatibility, GDF MPs were tested in combination with multiple particulate antigen formulations, including measles, gonorrhea, SARS-CoV-2, influenza A (H3N2), and Zika. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay was utilized to measure cell viability, while nitric oxide generation was measured with the Griess assay. Dendritic cell activation-associated surface marker expression was analyzed by flow cytometry using MHC I, MHC II, CD80, and CD40. Results: The particles showed consistent spherical morphology, sustained GDF release, and favorable cytocompatibility at concentrations up to 250 µg/mL, with reduced viability at higher concentrations. GDF MPs increased nitric oxide production and activation-associated marker expression, with responses benchmarked against Alum and AddaVax and comparable in several assay conditions. Increased autophagosome-associated fluorescence was also observed, suggesting modulation of autophagy-related cellular activity; however, direct antigen-processing or antigen-presentation assays are still required. Conclusions: Overall, these findings support GDF-loaded PLGA microparticles as an in vitro immunostimulatory particulate formulation suitable for further mechanistic and in vivo evaluation in vaccine-related systems. Full article

Human metapneumovirus (hMPV) is an important respiratory pathogen and a major cause of respiratory tract infections, particularly among vulnerable populations. Although hMPV was identified in 2001, it remains less extensively studied than other major respiratory viruses, such as influenza virus and respiratory syncytial virus (RSV), hindering the development of effective preventive and therapeutic strategies. This review examines the primary mechanisms by which hMPV evades host immune responses. The virus disrupts early innate immune signaling pathways, particularly those involved in the induction and signaling of antiviral interferons (IFNs) and modulates inflammatory responses. At the level of adaptive immunity, hMPV impairs T-cell activation and the development of long-lasting immunological memory, which may contribute to susceptibility to reinfection. The virus also alters the functions of several immune and structural cell types, including macrophages, dendritic cells, and respiratory epithelial cells. In addition, hMPV may modulate host microRNA expression to promote immune evasion and prolong infection. The recurrent nature of hMPV infections highlights the need to further investigate the immune-evasion mechanisms. Such research is essential for developing safer and more effective vaccines, antiviral agents, and immunomodulatory therapies. Full article

H9N2 avian influenza viruses pose a persistent zoonotic risk owing to their broad host adaptability. Between 2024 and 2025, two H9N2 isolates (ZHY1022B2 and ZHY0417A11) were recovered from quail flocks in Hebei, China. Phylogenetic analysis clustered their HA genes within the dominant B4.7.2 subclade, but diverged into two subgroups (B4.7.2.2 and B4.7.2.1). Of particular interest was ZHY0417A11, which displayed a multigenic reassortment pattern—its PB1 originated from an H3N8 virus, PA and PB2 from H3N3, NS from H10N3, and the M gene was nearly identical (99.32%) to a human H3N8 isolate, whereas the remaining HA, NA and NP segments maintained the H9N2 backbone. Despite the presence of the HA mammalian-adaptive markers (H191N, A198V and Q234L), both strains showed marked antigenic drift from the vaccine strain SS (BJ/94-like; R < 0.5), while retaining reactivity with currently circulating field strains. These findings argue for heightened vigilance in quail populations, given their role as mixing vessels, and highlight the limitations of current vaccine matching in light of ongoing H9N2 evolution. Full article