WHO: Influenza Update N° 529
June 4, 2025 | Emergency Situational Updates (For reporting Week 21, ending 25 May 2025)
In the Southern hemisphere, influenza activity remained stable in most countries with increases reported in a few countries in Temperate South America and Eastern Africa. Influenza positivity was elevated (>10%) in Tropical and Temperate South America (predominantly A(H1N1)pdm09), Southern Africa (predominantly A(H3N2)), Eastern Africa (predominantly A(H1N1)pdm09) and South-East Asia (predominantly A(H3N2)).
In the Northern hemisphere, influenza activity continued to decline or remained stable in most countries with increases reported in a few countries in Central America and the Caribbean and single countries in Tropical South America and Western Asia. Influenza positivity remained elevated in Central America and the Caribbean (predominantly A(H1N1)pdm09), Western, Southern and South-East Asia (A(H1N1), A(H3N2) and B viruses cocirculating in similar proportions). Read More
Mapping Behavioral and Social Drivers of Influenza Vaccine Uptake in Older Adults: A Scoping Review
Vaccines 2025, 13(6), 624, 10 June 2025.
Influenza vaccination plays a crucial role in reducing morbidity and mortality among older adults; however, uptake remains suboptimal, particularly in the post-COVID-19 pandemic. In many settings, countries have not recovered their influenza vaccine coverage rates to the same level as pre-COVID. Therefore, this scoping review systematically identified the behavioral and social drivers (BeSD) influencing influenza vaccination among older adults using the BeSD framework. A systematic search across five databases included quantitative, qualitative, and mixed-methods studies involving individuals aged 60 years and older. Data were charted across four BeSD domains: thinking and feeling, social processes, motivation, and practical issues. Thirty-nine studies from 24 countries were included. Key barriers encompassed safety concerns, misinformation, financial burdens, logistical challenges, and cultural and language barriers. While motivation was positively associated with vaccination intentions, the transition from intention to behavior remains underexplored, and practical issues have received comparatively limited research attention. These findings underscore the need for multifaceted, behaviorally informed interventions and greater inclusion of under-resourced settings to support equitable influenza vaccination strategies for healthy aging. Read More
Production and Immune Response Against Pandemic Influenza Candidate Vaccines as Preparedness Against the Circulating H5N1 Influenza Viruses
Vaccines 2025, 13(6), 620 June 8, 2025
H5N1 influenza viruses are spreading worldwide and threaten global public health. Preparedness is necessary to mitigate the worst-case scenario should an H5N1 influenza pandemic occur and justify the development of vaccines against circulating H5N1 viruses of concern. The production and characterization of egg-based split and inactivated H5Nx of three distinct monovalent antigens from clades 2.3.4.4b, 2.3.2.1c, and 2.3.4 were performed at an industrial scale. These antigens were formulated and their immune responses, when combined or not with IB160 squalene-based oil-in-water emulsion adjuvant in a rat model, were evaluated in a one- or two-dose immunization schedule. IgG antibodies, hemagglutination inhibitions, and microneutralization titers were measured for vaccine-induced immunity and cross-reactivity. Three monovalent vaccines from clades 2.3.4.4b, 2.3.2.1c, and 2.3.4 were produced at an industrial scale and characterized. The immune responses against the monovalent vaccines showed a clade-specific antibody response and the need to combine with IB160 adjuvant for a required immune response. The authors conclude that considering the candidate vaccine viruses (CVVs) with the testing potency reagents available and that the antibody response obtained against the CVVs produced was clade-specific, IDCDC RG-71A is the indicated CVV for the predominant currently circulating H5N1 influenza virus of clade 2.3.4.4b and must be combined with adjuvant to induce a higher and efficacious immune response in a two-dose immunization protocol. Read More
Antibody responses against influenza A decline with successive years of annual influenza vaccination
npj Vaccines 10, 11 (2025). https://doi.org/10.1038/s41541-024-01057-x
Influenza vaccine effectiveness and immunogenicity can be compromised with repeated vaccination. The authors assessed immunological markers in a cohort of healthcare workers (HCW) from six public hospitals around Australia during 2020–2021. Sera were collected pre-vaccination and ~14 and ~180 days post-vaccination and assessed in haemagglutination inhibition assay against egg-grown vaccine and equivalent cell-grown viruses. Responses to vaccination were compared by the number of prior vaccinations. Baseline sera were available for 595 HCW in 2020 and 1031 in 2021. 5% had not been vaccinated during five years prior to enrolment and 55% had been vaccinated every year. Post-vaccination titres for all vaccine antigens were lowest among HCW vaccinated in all 5-prior years and highest among HCW with 0 or 1 prior vaccinations, even after adjustment. This was observed for both influenza A subtypes and was dependent on pre-vaccination titre. Expanded cohorts are needed to better understand how this translates to vaccine effectiveness. Read More
Intranasal Administration of Cold-Adapted Live-Attenuated Eurasian Avian-like H1N1 Vaccine Candidate Confers Protection Against Different-Lineage H1N1 Viruses in Mice
Vaccines 2025, 13(6), 596. 30 May 2025
Eurasian avian-like (EA) H1N1 swine influenza viruses, with their persistent evolution and zoonotic potential, seriously threaten both swine and human health. The objective was to develop an effective vaccine against these viruses. Methods: A cold-adapted, temperature-sensitive live-attenuated influenza vaccine (LAIV) candidate, GX18ca, was developed. It was derived from the wild-type EA H1N1 strain A/swine/Guangxi/18/2011 (GX18) through serial passaging in embryonated eggs at temperatures decreasing from 33 °C to 25 °C. Its characteristics were studied in mice, including attenuation, immune responses (mucosal IgA, serum IgG, IFN-γ+ CD4+/CD8+ T-cell responses), and protective efficacy against homologous (GX18), heterologous EA H1N1 (LN972), and human 2009/H1N1 (SC1) viruses. Results: GX18ca showed cold-adapted and temperature-sensitive phenotypes. In mice, it was attenuated, with viral titers in the nasal turbinates and lungs reduced 1000–10,000-fold compared to the wild-type strain, and it cleared by day 5 post infection. Intranasal immunization elicited strong cross-reactive immune responses. Mucosal IgA had broad reactivity, and serum IgG titers reached high levels. IFN-γ+ CD4+/CD8+ T-cell responses were detected against all the tested viruses. A single dose of GX18ca fully protected against GX18 and LN972 challenges, and two doses significantly reduced SC1 lung viral loads, preventing mortality and weight loss. Conclusions: GX18ca is a promising LAIV candidate. It can induce broad immunity, addressing the cross-protection gaps against evolving EA H1N1 SIVs and zoonotic H1N1 variants, which is crucial for swine influenza control and pandemic preparedness. Read More
Antigenic Characterization of H1N1 Influenza Viruses That Circulated During the 2019–2020 Season in Philadelphia, Pennsylvania
Influenza and Other Resp Viruses 01 June 2025 https://doi.org/10.1111/irv.70104
During the 2019–2020 influenza season, researchers studied serum antibodies from patients infected with different clades of H1N1 influenza A viruses (IAVs) and influenza B viruses (IBVs) within the University of Pennsylvania Health System. By sequencing H1N1 viruses from nasopharyngeal swabs and conducting hemagglutination inhibition assays, they found that most IAV infections were caused by clade 6B.1A.5a.1 and 6B.1A.5a.2 H1N1 viruses, which had mutations in key hemagglutinin antigenic sites. Both H1N1- and IBV-infected individuals showed stronger antibody responses to the 6B.1A.1 H1N1 vaccine strain than to the circulating H1N1 clades, with 6B.1A.5a.2-infected patients exhibiting significantly higher antibody titers against the vaccine strain, indicating that this clade may evade antibodies from prior vaccinations or infections. Overall, the study suggests that antibodies in most patients, regardless of infection type, had reduced effectiveness against the circulating H1N1 strains. Read More
Chimeric hemagglutinin and M2 mRNA vaccine for broad influenza subtype protection
npj Vaccines volume 10, Article number: 113 (2025)
Since multiple and unpredicted influenza viruses cause seasonal epidemics and even high-risk pandemics, developing a universal influenza vaccine is essential to provide broad protection against various influenza subtypes. Combined with the mRNA lipid nanoparticle-encapsulated (mRNA-LNP) vaccine platform and chimeric immunogen strategy, we developed a novel cocktail mRNA vaccine encoding chimeric HAs (cH5/1-BV, cH7/3) and intact M2 (termed Fluaxe), which confers broad protection against major circulating IAVs and IBVs, as well as highly pathogenic avian influenza. Two-dose intramuscular immunization of Fluaxe in mice elicited cross-reactive neutralizing antibodies, T cell responses, and long-lived immunity, resulting in robust protection against multiple lethal influenza virus infections and severe acute lung injuries. In particular, intramuscular administration stimulated systemic immunity together with a prominent lung tropism of memory cells. Moreover, Fluaxe immunization inhibited the inflammatory response induced by influenza infection. In summary, we conclude that Fluaxe can elicit broad cross-protection against numerous influenza subtypes. Read More
Excess pneumonia and influenza mortality in Nevada during the COVID-19 pandemic (March 2020-December 2021): Implications for disaster preparedness
International Journal of Disaster Risk Reduction Volume 126, August 2025, 105630
The COVID-19 pandemic disrupted pneumonia and influenza (P&I) mortality patterns, altering seasonality and increasing disparities across demographic and geographic groups. Prior studies often relied on aggregate estimates that obscured subgroup-specific disparities. This study analyzes excess P&I mortality in Nevada as a case study for pandemic-related mortality impacts through a disaster risk reduction and social determinants of health framework to quantify excess deaths, assess disparities, and evaluate COVID-19’s contribution. Using death certificate data from Nevada State Vital Records spanning January 2015 to December 2021, P&I deaths were identified using ICD-10 codes (influenza: J09.0-J11.9, pneumonia: J12.0-J18.9, COVID-19: U07.1). A Zero-Inflated Negative Binomial model estimated expected P&I mortality based on pre-pandemic reference period (January 2015–February 2020), with excess deaths calculated as the difference between observed and expected mortality. Demographic and geographic disparities were quantified. Findings showed Nevada recorded 6,234 excess respiratory disease deaths, a 3.95-fold (295%) increase above expected levels. COVID-19-associated deaths comprised 75.3% of P&I deaths and 4,506 excess deaths; non-COVID-19 P&I deaths showed no significant excess. Disparities were most pronounced among males (4.33-fold, 333% increase), adults aged 25-64 (4.97-fold, 397%), and Hispanics (7.92-fold, 692%), although the greatest number of deaths occurred among adults aged ≥65. Frontier regions had the greatest mortality burden among regions (3.98-fold, 298%). These findings show the pandemic drastically impacted respiratory disease mortality patterns, disproportionately affecting working-aged adults, racial/ethnic minorities, and frontier communities. This study highlights the need for strengthened healthcare infrastructure, improved emergency response, and equitable preparedness policies. Read More
Impact of short-term weather variability on influenza incidence under climate change
Clim Res 94:55-69 (2025). https://doi.org/10.3354/cr01752
Influenza incidence has been proven to be closely associated with low temperatures. However, the role of temperature fluctuations in affecting influenza incidence is less quantified, especially in the context of global warming. This study constructed a short-term weather variability index (SWVI) to measure the cumulative fluctuations of minimum temperature between 2 consecutive weeks and comprehensively analyzed the impact of SWVI on current and future risks of influenza incidence in the mid-latitude region of Hubei Province, China. Influenza-like illnesses (ILI) data (2009-2020), meteorological observation data from 76 national stations (1979-2020), 10 global climate models in the Coupled Model Intercomparison Project Phase 6 (CMIP6) and distributed lag nonlinear modeling were used for analysis. The results showed that (1) the intra-annual variation of SWVI and the percentage of ILI (ILI%) in Hubei exhibited similar bimodal structures. A more significant correlation was detected between SWVI and ILI% than with sustained low temperatures, suggesting that SWVI may serve as a stimulus for influenza incidence. (2) From winter to spring, the response of relative risk (RR) of ILI% to SWVI was faster and greater than to low temperature. The most significant impact of SWVI on influenza incidence was observed at a short-term lag of 0 wk, with the highest increase in RR of ILI% recorded at 84.1% (95% confidence interval [CI]: 25.7-169.6%) for each 1°C increase in SWVI. In age-stratified analysis, younger people were more susceptible to weather variability than the elderly. (3) In the past 40 yr, the annual SWVI increased consistently, particularly in central and eastern Hubei. CMIP6 projections showed that SWVI would continue to increase with a stronger amplitude under scenarios of higher emissions. The risk of influenza incidence caused by short-term weather variability will inevitably increase, with the greatest risk anticipated at the end of the 21st century (76.4%). Read More
Maintaining the value of influenza vaccination – the shift from quadrivalent to trivalent vaccines: an expert review
Expert Review of Vaccines Volume 24, 2025 – Issue 1. Published 1 June 2025
This review provides an expert perspective on the sustained value of seasonal influenza vaccines as they transition from quadrivalent to trivalent formulations, based on apparent elimination of the B/Yamagata strain from circulation and subsequent advice from the World Health Organization (WHO) to remove the B/Yamagata antigen from influenza vaccines. Influenza has a high clinical and economic burden globally. However, coronavirus disease 2019 has created new challenges for managing seasonal influenza by amplifying vaccine hesitancy. Understanding why influenza virus circulation is monitored and vaccines subsequently updated is important for all relevant stakeholders to maintain confidence in the value of seasonal influenza vaccination. The experts conclude that The move from quadrivalent to trivalent influenza vaccines is a result of findings from strain surveillance. Continued surveillance and targeting of vaccines against strains most commonly in circulation to keep effectiveness high, and ensure the highest value of vaccination is vital to prevent influenza infection and severe illness, thus reducing pressure on healthcare systems and reducing the economic impact of influenza outbreaks. Read More