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16 pages, 1545 KB  
Article
Characterization of Seasonal Trivalent Influenza Vaccine Formulated with Different Ratios (v/v) of Squalene-Containing IB160 Adjuvant in One- or Two-Vial Presentations
by Daniela Cajado-Carvalho, Paulo Newton Tonolli, Verônica de Moraes Manzato, Lívia Mendonça Munhoz Dati, Mahyumi Fujimori, Patrícia Antonia Estima Abreu, Christian Savio Silva, Vitor Anselmo Sakihara, Bianca Pereira Carvalho Holanda, Douglas Gonçalves de Macedo, Priscila Comone, Alexandre Bimbo, Esper George Kallás, Ricardo das Neves Oliveira, Milena Apetito Akamatsu and Paulo Lee Ho
Vaccines 2026, 14(9), 789; https://doi.org/10.3390/vaccines14090789 (registering DOI) - 9 Sep 2026
Abstract
Background/Objectives: Adjuvanted influenza vaccines are critical to enhance immune responses in high-risk populations, such as the elderly. While initial studies relied on a two-vial system with antigen and adjuvant mixing prior to immunization, this study evaluated the feasibility, immunogenicity, and 12-month stability of [...] Read more.
Background/Objectives: Adjuvanted influenza vaccines are critical to enhance immune responses in high-risk populations, such as the elderly. While initial studies relied on a two-vial system with antigen and adjuvant mixing prior to immunization, this study evaluated the feasibility, immunogenicity, and 12-month stability of a one-vial formulation combining a Trivalent Influenza Vaccine (TIV) with the locally produced squalene-based oil-in-water emulsion IB160. Methods: Formulations were evaluated by testing TIV:IB160 (v/v) ratios (1:1, 2:1, 3:1) in an animal model, measuring HI antibodies as the primary immunogenicity metric, complemented by qualitative strain-specific total IgG screening by ELISA. One-vial and two-vial strategies were also compared regarding immune responses. Formulations stabilities were evaluated at 6.0 °C ± 2.0 °C in one-and two-vial systems by monitoring physicochemical features and their antigenic responses, measuring hemagglutinin content of the formulated vaccines, and long-term HI antibody responses. Results: The 2:1 and 1:1 (v/v) formulation ratios (15 µg TIV:IB160) induced significantly higher HI titers across all tested strains (A/H3N2/Thailand, A/H1N1/Victoria, and B/Austria) when compared to non-adjuvanted TIV or adjuvanted TIV in the 3:1 ratio. Both the one and two-vial strategies showed significantly higher HI antibody responses than the non-adjuvanted control group (p < 0.05), with no significant differences observed between the delivery formats. Indeed, the one-vial formulation with 1:1 and 2:1 ratios remained stable for 12 months, preserving TIV antigenicity, IB160 emulsion integrity, and robust immunogenicity. Conclusions: One- and two-vial formulations are viable, stable, and highly immunogenic alternatives for adjuvanted TIV in 2:1 and 1:1 (v/v) formulation ratios (15 µg TIV:IB160). One-vial format simplifies immunization logistics, minimizes operational errors, and is more indicated for routine use, while the two-vial system remains a versatile asset for emergency responses. Full article
(This article belongs to the Special Issue Vaccine Development for Influenza Virus: 2nd Edition)
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22 pages, 930 KB  
Review
Developing Antiviral Vaccines Based on Attenuated Salmonella
by Ethan Ou and Fenyong Liu
Pathogens 2026, 15(9), 955; https://doi.org/10.3390/pathogens15090955 - 8 Sep 2026
Abstract
Attenuated Salmonella strains are a promising gene delivery vector in the development of vaccines targeting various human diseases. For example, the Ty21a vaccine is a Salmonella-based vaccine that elicits a robust local, cellular, and systemic immune response against Salmonella typhi infection. Human [...] Read more.
Attenuated Salmonella strains are a promising gene delivery vector in the development of vaccines targeting various human diseases. For example, the Ty21a vaccine is a Salmonella-based vaccine that elicits a robust local, cellular, and systemic immune response against Salmonella typhi infection. Human immunodeficiency virus (HIV) is responsible for the AIDS pandemic and requires lifelong treatment to manage. Human papillomavirus (HPV) is the cause of the vast majority of cervical cancer cases in the global population. Influenza is a seasonal, pandemic virus that can lead to high death tolls in humans and livestock and considerable financial losses. In this review, we outline current methods of protection and treatment for HIV, HPV, and influenza, as well as how a versatile Salmonella-based gene delivery vector’s mechanism of action can lead to immunity. We also describe several studies that utilize many of these Salmonella-based vector vaccines to provide protection against infection with these viruses, as many of these Salmonella-based vectors exhibit different factors that may enhance their gene delivery, immune responses, and post-delivery clearance out of host cells. Finally, we discuss the benefits and drawbacks of using Salmonella-based vaccines and future directions for these vaccine candidates, as well as the implications of introducing these vaccines into the current landscape. Full article
(This article belongs to the Section Vaccines and Therapeutic Developments)
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13 pages, 1766 KB  
Article
Perceived Vaccination Knowledge and Self-Reported Uptake in a Nationwide Heart Failure Telemonitoring Cohort in France
by Patrick Jourdain, Rémi Esser, Nicolas Girerd, Abdelhakim Hacil, Nathalie Berkane, Hélène Benchimol, Franck Albert, Annabelle Jagu, François Picard, Mihaela Ionescu, Wafa Ben Ghezala, Nicolas Pages, Sophie Nisse-Durgeat and Olivier Hanon
J. Clin. Med. 2026, 15(17), 6933; https://doi.org/10.3390/jcm15176933 - 7 Sep 2026
Abstract
Background/Objectives: Patients with heart failure (HF) are vulnerable to vaccine-preventable infections, yet vaccination data remain limited. We assessed perceived vaccination knowledge, attitudes, self-reported vaccine receipt, and variation by age, sex, region, and delivery pathway among digitally connected patients with HF enrolled in [...] Read more.
Background/Objectives: Patients with heart failure (HF) are vulnerable to vaccine-preventable infections, yet vaccination data remain limited. We assessed perceived vaccination knowledge, attitudes, self-reported vaccine receipt, and variation by age, sex, region, and delivery pathway among digitally connected patients with HF enrolled in a nationwide telemonitoring program. Methods: This cross-sectional electronic survey was conducted from 5 to 28 November 2025, during the ongoing 2025–2026 influenza and COVID-19 vaccination campaigns, among app-connected Satelia® Cardio participants across France. Of 4856 invited app-connected patients, 1100 completed the questionnaire (response rate: 22.7%). Uptake of seasonal influenza and COVID-19 booster vaccination for the 2025–2026 season and lifetime receipt of pneumococcal, tetanus–diphtheria–pertussis–poliomyelitis (Tdap-polio), and herpes zoster vaccines were analyzed using Wilson 95% confidence intervals (CIs), age-adjusted logistic regression, and regional models adjusted for age and sex. Results: Respondents had a mean age of 71.5 years (SD: 12.6), and 718 (65.3%) were men. Overall, 87.5% considered vaccination useful, 96.0% knew where to be vaccinated, and 55.1% wanted telemonitoring-based reminders. Current-season reported vaccination was 62.2% for influenza and 31.4% for the COVID-19 booster, whereas lifetime self-reported receipt was 38.5% for Tdap-polio, 34.5% for pneumococcal vaccination, and 11.5% for herpes zoster. Influenza and COVID-19 uptake increased with age, whereas pneumococcal uptake peaked at 65–74 years. Pneumococcal receipt was higher in women than men (42.2% vs. 30.4%; age-adjusted odds ratio [aOR], 1.67; 95% confidence interval [CI], 1.29–2.17; p < 0.001). Community pharmacies delivered most influenza and COVID-19 vaccinations. Conclusions: Vaccination attitudes were favorable, while current-season vaccination and lifetime-reported vaccine receipt showed distinct patterns across age groups. These descriptive findings identify potential target groups for future telemonitoring-based preventive interventions, whose effectiveness requires prospective evaluation. Full article
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15 pages, 240 KB  
Article
Factors Associated with Intention to Be Vaccinated Against Seasonal Influenza in Healthcare Workers: A Cross-Sectional Study Assessing Health Belief Model Constructs in Serbia
by Larisa Vujnovic, Biljana Kilibarda, Sofija Jovanovic, Dragana Dimitrijevic, Milunka Milinkovic, Zoran Bukumiric and Verica Jovanovic
Vaccines 2026, 14(9), 763; https://doi.org/10.3390/vaccines14090763 - 1 Sep 2026
Viewed by 209
Abstract
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, [...] Read more.
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
(This article belongs to the Special Issue Factors Affecting Influenza Vaccine Uptake)
16 pages, 3686 KB  
Article
Genetic Variability and Evolutionary Dynamics of A(H1N1)pdm09 in Italy Before, During, and After the COVID-19 Pandemic
by Maria Perra, Ilaria Deplano, Ilenia Azzena, Chiara Locci, Giancarlo Ceccarelli, Dong Keon Yon, Francesco Branda, Massimo Ciccozzi, Marco Casu, Alessandra Borsetti, Daria Sanna and Fabio Scarpa
Pathogens 2026, 15(9), 920; https://doi.org/10.3390/pathogens15090920 - 1 Sep 2026
Viewed by 143
Abstract
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 [...] Read more.
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
(This article belongs to the Section Epidemiology of Infectious Diseases)
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10 pages, 2270 KB  
Case Report
Point-of-Care Ultrasound-Guided Management of Fulminant Influenza A(H3) with Staphylococcus aureus Necrotizing Pneumonia and Acute Cardiopulmonary Failure: A Case Report
by Luigi Vetrugno, Giovanni Serena, Stefania Buttera, Pierpaolo Accolla, Davide Pecori, Irene Batticci, Davide Stolfo, Massimo Imazio, Igor Vendramin and Flavio Bassi
Healthcare 2026, 14(17), 2766; https://doi.org/10.3390/healthcare14172766 - 1 Sep 2026
Viewed by 163
Abstract
Background: Seasonal influenza is typically a self-limiting illness in healthy young adults, but severe and potentially life-threatening complications can occur. Influenza A infection may predispose patients to secondary bacterial infections, including Staphylococcus aureus pneumonia and bacteremia, which can rapidly progress to necrotizing pneumonia, [...] Read more.
Background: Seasonal influenza is typically a self-limiting illness in healthy young adults, but severe and potentially life-threatening complications can occur. Influenza A infection may predispose patients to secondary bacterial infections, including Staphylococcus aureus pneumonia and bacteremia, which can rapidly progress to necrotizing pneumonia, acute respiratory distress syndrome (ARDS), and cardiovascular dysfunction. Case Presentation: We report the case of a young adult with influenza A(H3) infection complicated by Staphylococcus aureus bacteremia, necrotizing pneumonia, ARDS, and biventricular dysfunction. The patient experienced rapid cardiopulmonary deterioration requiring advanced critical care support, including extracorporeal membrane oxygenation (ECMO) and left ventricular unloading. Serial point-of-care ultrasound (POCUS) was central to clinical management, enabling early recognition of worsening respiratory and cardiac function and guiding timely escalation of supportive strategies. Conclusions: This case highlights the potential severity of influenza-associated complications even in young and previously healthy individuals. Repeated POCUS assessment can play a pivotal role in detecting rapid cardiopulmonary deterioration and guiding advanced interventions. Efficient hub-and-spoke organization may further support timely referral and management of critically ill patients requiring ECMO and specialized care. Full article
(This article belongs to the Section Clinical Care)
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14 pages, 1754 KB  
Article
Real-World Effectiveness of Egg-Based Inactivated Influenza Vaccines Against Influenza Among Children Aged 6–59 Months During the 2025/26 Season in Shenzhen Area, China: A Retrospective Cohort Study
by Hui-Ling Tan, Wu Li, Yu Zeng, Rui-Kun Zeng, Jia-Xin Zhong and Hou-Ming Wei
Vaccines 2026, 14(9), 762; https://doi.org/10.3390/vaccines14090762 - 31 Aug 2026
Viewed by 149
Abstract
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 [...] Read more.
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 4 August 2025 to 8 February 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 8 February 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
(This article belongs to the Special Issue The Effectiveness of Influenza Vaccine)
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16 pages, 1158 KB  
Article
Epidemiology of SARS-CoV-2, Influenza, RSV, and Human Metapneumovirus Across the COVID-19 Era: An Eight-Year Tertiary-Center Study in Saudi Arabia
by Lama Alzamil, Arwa Bagasi, Zeina S. Alkudmani, Hamad M. Almatrudi, Abdulrahman F. Alrezaihi and Abdulaziz M. Almuqrin
Pathogens 2026, 15(9), 918; https://doi.org/10.3390/pathogens15090918 - 31 Aug 2026
Viewed by 248
Abstract
Background: Respiratory tract infections (RTIs) caused by viruses are a public health problem, contributing to hospital admissions and morbidity worldwide. The COVID-19 pandemic substantially altered the detection patterns of respiratory viruses through public health interventions. Longitudinal data on these changes and viral seasonality [...] Read more.
Background: Respiratory tract infections (RTIs) caused by viruses are a public health problem, contributing to hospital admissions and morbidity worldwide. The COVID-19 pandemic substantially altered the detection patterns of respiratory viruses through public health interventions. Longitudinal data on these changes and viral seasonality remain limited in Saudi Arabia. This eight-year study evaluated epidemiological and seasonal patterns of major respiratory viruses across the COVID-19 era at a major Saudi tertiary care center. Methods: A retrospective observational study was conducted at King Khalid University Hospital, Riyadh, from October 2017 to December 2025. PCR-confirmed detections for SARS-CoV-2, Influenza A, Influenza B, respiratory syncytial virus (RSV), and human metapneumovirus (HMPV) were extracted from the hospital Laboratory Information System. Demographics, co-detection, seasonality, and length of stay (LOS) were analyzed across four eras spanning the pre-COVID-19, lockdown, restriction, and post-restriction periods using descriptive statistics, the Kruskal–Wallis test, and multivariable negative binomial regression. Results: Among 5708 confirmed respiratory viral detection episodes, SARS-CoV-2 was the most frequently detected (52.5%), followed by Influenza A (19.1%), RSV (16.4%), Influenza B (8.4%), and HMPV (3.6%). Before the pandemic, Influenza A accounted for the largest proportion of detected episodes (71.1%), with detections clustering particularly during autumn and winter seasons, whereas SARS-CoV-2 accounted for the majority of detected episodes during the lockdown and restriction eras (97.4% and 93.2%). The post-restriction era became more diverse, with RSV being detected in substantial proportions (28.3%), showing prominent winter activity. RSV and HMPV predominantly affected children aged 0–5 years, whereas SARS-CoV-2 was more frequently detected among older adults. Among adults, older age was associated with prolonged LOS; Influenza A and HMPV were associated with shorter stays compared to SARS-CoV-2. Among children, no virus was independently associated with LOS after adjustment for age and sex; however, older age was associated with longer hospital stays. Conclusion: The observed detection patterns of major respiratory viruses shifted substantially across the COVID-19 eras, with notable post-restriction diversification among observed positive detections. LOS was associated with age in both adults and children and with virus type among adults, supporting continued surveillance to guide preventive and clinical strategies. Full article
(This article belongs to the Section Epidemiology of Infectious Diseases)
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13 pages, 1942 KB  
Article
Epidemiological and Molecular Characterization of Human Metapneumovirus (HMPV) in Children Under 14 Years of Age in Shijiazhuang City, China
by Sihan Li, Caixiao Jiang, Minghao Geng, Nana Guo, Wentao Wu, Ziyi Pang, Xianlei Zhou, Jingyi Xue, Yaojia Bian, Jiuqi Jia, Xu Han, Yan Li and Qi Li
Pathogens 2026, 15(9), 909; https://doi.org/10.3390/pathogens15090909 - 28 Aug 2026
Viewed by 152
Abstract
Objective: The objectives of this study were to analyze the epidemiological characteristics and whole-genome features of human metapneumovirus (HMPV) among children under 14 years of age in Shijiazhuang during 2022–2025, enrich the whole-genome data of HMPV in China, and provide a basis for [...] Read more.
Objective: The objectives of this study were to analyze the epidemiological characteristics and whole-genome features of human metapneumovirus (HMPV) among children under 14 years of age in Shijiazhuang during 2022–2025, enrich the whole-genome data of HMPV in China, and provide a basis for further understanding the genetic diversity of the virus and for its prevention, control, and transmission intervention. Methods: A total of 1920 cases of acute respiratory infection were enrolled from three sentinel hospitals in Shijiazhuang. Nucleic acid screening was performed using real-time PCR. Whole-genome sequencing was conducted on 25 positive samples. Phylogenetic trees were constructed using the neighbor-joining method in MEGA, and nucleotide and amino acid sequence identity analyses were performed. Results: The overall detection rate of HMPV from 2022 to 2025 was 4.17%. A prominent peak in winter 2024 was the major distinguishing feature. Temporally, both influenza-like illness (ILI) and severe acute respiratory infection (SARI) cases showed marked seasonality during 2022–2025, with high-incidence periods in December–March and April–June. BLAST alignment and phylogenetic analysis showed that among the 25 sequenced HMPV specimens, genotype B2 was the most frequently identified genotype (13/25, 52%). Conclusions: HMPV epidemics in Shijiazhuang during 2022–2025 mainly occurred in winter–spring and spring–summer, with a notable detection peak in December 2024. The B2 genotype predominated among the sequenced HMPV isolates obtained in this study. The amino acid variation in the G gene was significantly higher than that in other genomic regions. Full article
(This article belongs to the Section Viral Pathogens)
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14 pages, 2275 KB  
Article
Estimating the Relative Vaccine Efficacy of mRNA-1010 to High-Dose Influenza Vaccine in Adults ≥65 Years Using a Correlate of Protection Framework
by Van Hung Nguyen, Ethan Settembre, John Youhanna, Ekkehard Beck, Nicolas Van de Velde and Keya Joshi
Vaccines 2026, 14(9), 750; https://doi.org/10.3390/vaccines14090750 - 28 Aug 2026
Viewed by 281
Abstract
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) [...] Read more.
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
(This article belongs to the Section Influenza Virus Vaccines)
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18 pages, 6167 KB  
Review
Population Immunity to Influenza Neuraminidase: From Immune Imprinting to Pandemic Preparedness
by Kong Yen Liew, Tri Komala Sari and Yee-Joo Tan
Vaccines 2026, 14(9), 748; https://doi.org/10.3390/vaccines14090748 - 28 Aug 2026
Viewed by 291
Abstract
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, [...] Read more.
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
(This article belongs to the Special Issue Immunity to Influenza Viruses and Vaccines: 2nd Edition)
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25 pages, 831 KB  
Article
High-Impact Weather Types and Characteristics That Induce Severe Influenza Episodes in Langfang, China
by Liping Guo, Lixia Yan, Yuzhuo Wang, Qiqi Liu, Xiaofei Tian, Yanjing Zeng, Jianhui Bai, Yudu Zhou and Xianghan Zhang
Atmosphere 2026, 17(9), 836; https://doi.org/10.3390/atmos17090836 - 27 Aug 2026
Viewed by 211
Abstract
To thoroughly investigate the effects of high-impact weather and compound weather types on the triggering of severe influenza outbreaks and to effectively support the implementation of related weather risk forecasting services, methodologies from synoptic meteorology, climatology, medical statistics, time-lag effect, seasonally stratified correlation [...] Read more.
To thoroughly investigate the effects of high-impact weather and compound weather types on the triggering of severe influenza outbreaks and to effectively support the implementation of related weather risk forecasting services, methodologies from synoptic meteorology, climatology, medical statistics, time-lag effect, seasonally stratified correlation analysis, and SPSS (IBM SPSS Statistics 25) software were integrated, and severe influenza episodes in Langfang, China, were explored. The research encompasses the collection and processing of meteorological, influenza, and air pollution data; the study and analysis of the characteristics of severe influenza occurrences and associated meteorological conditions; the categorization of high-impact weather types, compound patterns, and their associated influenza distribution characteristics that induce severe influenza episodes; the analysis of the synergistic effects of air pollution coupled with high-impact weather events such as haze on triggering severe influenza; and the assessment of the effects of social prevention and control measures in mitigating severe influenza outbreaks. This study establishes an influenza risk forecasting grade based on high-impact weather classification, providing a scientific reference for the public to defend against influenza. Full article
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17 pages, 1857 KB  
Article
Memory B Cell Repertoire of a Repeatedly Vaccinated Individual Includes Influenza Hemagglutinin-Specific Cross-Group Binders with Affinity Beyond A(H1N1)pdm09 and A(H3N2) Seasonal Strains
by Margarita Mishina, Christopher M. Horn, Zachary Ende, Vasiliy Mishin, Crystal Holiday, Sujatha Seenu, Jason R. Wilson, Weiping Cao, Mili Sheth, Dhwani Batra, Jessie Chang, Paul Carney, Min Z. Levine, James Stevens, Michael R. Weigand, Ian A. York and Shivaprakash Gangappa
Vaccines 2026, 14(9), 742; https://doi.org/10.3390/vaccines14090742 - 27 Aug 2026
Viewed by 271
Abstract
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 [...] Read more.
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
(This article belongs to the Special Issue Immunity to Influenza Viruses and Vaccines: 2nd Edition)
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17 pages, 1528 KB  
Article
Patterns and Predictors of Influenza Vaccination Uptake Among Healthcare Personnel in Kuwait: A Nationwide Multi-Season Study
by Saleh Alsarhan, Fatema Alkhulaifi and Lolwah Alzafiri
Vaccines 2026, 14(8), 712; https://doi.org/10.3390/vaccines14080712 - 19 Aug 2026
Viewed by 351
Abstract
Background/Objectives: Healthcare personnel (HP) are a priority group for seasonal influenza vaccination due to their increased occupational exposure and potential to transmit influenza in healthcare settings. This study examined patterns and factors associated with in-season influenza vaccination uptake among HP in Kuwait. [...] Read more.
Background/Objectives: Healthcare personnel (HP) are a priority group for seasonal influenza vaccination due to their increased occupational exposure and potential to transmit influenza in healthcare settings. This study examined patterns and factors associated with in-season influenza vaccination uptake among HP in Kuwait. Methods: A nationwide observational study was conducted using Ministry of Health (MOH) administrative records covering the 2022/2023 through 2024/2025 influenza seasons. A person–season dataset was constructed, comprising one observation per HP for each of the three seasons. The primary outcome was in-season influenza vaccination, defined as receipt of an influenza vaccine between September and March of a given study season. Independent variables included age, sex, nationality, governorate of residence, profession, managerial position, previous-year influenza vaccination status, and pre-season sickness absence duration (days). Generalized estimating equations (GEE) logistic regression model with an exchangeable correlation structure was used to estimate factors associated with vaccination uptake. Results: The final analytic dataset included 48,886 HP contributing 146,658 person–season observations across three influenza seasons. Overall, in-season vaccination uptake was 8.7%, and repeated vaccination across seasons was uncommon. Older age, male sex, non-Kuwaiti nationality, and being a physician were independently associated with higher odds of in-season influenza vaccination. Previous-year influenza vaccination was the strongest predictor of current-season vaccination uptake (aOR 2.01, 95% CI 1.87–2.16; p < 0.001). Compared with HP with no pre-season sickness absence, those with 1–3 pre-season sickness absence days had slightly higher adjusted odds of vaccination (aOR 1.08, 95% CI 1.03–1.14), whereas those with ≥8 days had lower adjusted odds (aOR 0.91, 95% CI 0.85–0.97). Conclusions: In-season influenza vaccination uptake among HP in Kuwait was low across three consecutive influenza seasons, with limited continuity of annual vaccination. Previous-year vaccination was the strongest predictor of current-season vaccination uptake, while the association between pre-season sickness absence and vaccination varied by absence duration. These findings support continued efforts to improve and sustain in-season influenza vaccination uptake among HP, while further research is needed to clarify the factors underlying vaccination decisions. Full article
(This article belongs to the Section Influenza Virus Vaccines)
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14 pages, 3083 KB  
Article
Influenza Vaccine Effectiveness Against Pneumonia and COPD Exacerbations Among Patients with Chronic Obstructive Pulmonary Disease in Thailand: A National Test-Negative Design Study, 2013–2024
by Sutthinan Chawalchitiporn, Pichaya Tantiyavarong, Jiraphut Kittiwatanachod, Suriya Naosri, Kriengkrai Prasert and Prabda Praphasiri
Vaccines 2026, 14(8), 711; https://doi.org/10.3390/vaccines14080711 - 18 Aug 2026
Viewed by 373
Abstract
Background/Objectives: Influenza infection is a major trigger of pneumonia and acute exacerbations among patients with chronic obstructive pulmonary disease (COPD). However, national laboratory-confirmed evidence on influenza vaccine effectiveness (VE) in this high-risk population remains limited. This study aimed to estimate the effectiveness of [...] Read more.
Background/Objectives: Influenza infection is a major trigger of pneumonia and acute exacerbations among patients with chronic obstructive pulmonary disease (COPD). However, national laboratory-confirmed evidence on influenza vaccine effectiveness (VE) in this high-risk population remains limited. This study aimed to estimate the effectiveness of seasonal influenza vaccination against influenza-associated pneumonia and COPD exacerbations among patients with COPD in Thailand. Methods: We conducted a nationwide retrospective test-negative design study using administrative healthcare data from the National Health Security Office linked with laboratory-confirmed influenza surveillance data between 1 June 2013 and 31 May 2025, covering twelve influenza seasons (2013–2024). COPD-related clinical episodes among patients aged ≥40 years who presented with pneumonia or acute exacerbation of COPD and underwent RT-PCR testing for influenza were included. Modified Poisson regression with cluster-robust standard errors was used to estimate adjusted risk ratios (RRs), and VE was calculated as (1 − adjusted RR) × 100. Results: A total of 606,072 COPD-related clinical episodes were included, of which 192,224 (31.7%) were influenza-positive. The overall adjusted VE against influenza-associated pneumonia was 55.9% (95% CI: 47.3–63.1), while VE against influenza-associated COPD exacerbations was 67.0% (95% CI: 48.8–78.8). VE estimates were broadly similar across age groups and consistent across COPD severity strata. Conclusions: Seasonal influenza vaccination was associated with substantial protection against influenza-associated pneumonia and COPD exacerbations among patients with COPD in Thailand. Full article
(This article belongs to the Section Influenza Virus Vaccines)
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