Near real-time data on the #human neutralizing #antibody #landscape to #influenza virus in summer of 2026 shows antigenic advance of #H3N2 subclade K region D mutants and #H1N1 D.3.1.1 Sa mutants

 

Abstract

Human seasonal influenza evolves rapidly, necessitating twice yearly decisions about whether to update the strains in the vaccine. To help inform this decision, we have been using high-throughput sequencing-based neutralization assays to make twice yearly measurements of how recent human sera neutralize current human H3N2 and H1N1 strains. Here we provide the third installment in this series of measurements by reporting 47,851 titers representing neutralization of 148 viral strains by 325 human sera collected between April and August of 2026. Our measurements show that new H3N2 subclade K strains with mutations in antigenic region D and new H1N1 subclade D.3.1.1 strains with mutations in antigenic region Sa (such as G155E) have reduced neutralization by human sera, with notable heterogeneity in the impact of some of these mutations across sera from different individuals. This paper is accompanied by an interactive summary (https://jbloomlab.github.io/flu-seqneut-2026/summary.html) that enables detailed exploration of the results, and all titer data are publicly available for further analysis to aid vaccine antigen selection and studies of viral evolution.

Competing Interest Statement

JDB consults for Pfizer, GSK, Apriori Bio, and Merck. JDB has received stock options in the Vaccine Company. JDB is an inventor on Fred Hutch licensed patents related to techniques to characterize the antigenic effects of viral variation. SEH is a co-inventor on patents that describe the use of nucleoside-modified mRNA as a vaccine platform. SEH reports receiving consulting fees from Sanofi, Pfizer, Lumen, Novavax, and Merck. ALG reports contract testing to UW from Abbott, Cepheid, Novavax, Pfizer, Janssen, Assembly Biosciences, Aicuris, Innovative Molecules, and Hologic, research support from Gilead, personal consulting fees from Arisan Therapeutics, outside of the described work. JAE reports support to her institution from GSK, Pfizer, Moderna, and is a consultant for GSK, Pfizer, Merck, Meissa vaccines, Moderna, and Shionogi. ST reports research funding from Pfizer for a separate study.

Funder Information Declared

National Institute of Allergy and Infectious Diseases, R01AI165821, F30AI186284, 75N93021C00015

Howard Hughes Medical Institute, https://ror.org/006w34k90

Source: 

Link: https://doi.org/10.64898/2026.09.15.751855

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#Taiwan, Seasonal #Influenza and #COVID19 #Epidemics Weekly #Update (CDC, September 15 '26): #H1N1pdm09 flu virus & #SARS-CoV-2 PQ.16.1.1 predominated

 

{Excerpts}

(...)

    The CDC pointed out that the domestic influenza epidemic is rising and in its epidemic season. 

    In the 36th week (September 6th-12th), there were 136,796 outpatient and emergency room visits for influenza-like illnesses, an increase of 16.5% compared to the previous week. 

    Additionally, last week (September 8th-14th), there were 92 new cases of severe influenza complications (79 H1N1, 5 H3N2, and 8 untyped A cases) and 21 deaths (18 H1N1, 2 H3N2, and 1 untyped A case). 

    Laboratory monitoring data shows that the influenza virus currently circulating in the community is mainly type A, with type A H1N1 accounting for 82.2%. 

    This flu season has seen a cumulative total of 1,421 severe cases (800 H1N1, 503 H3N2, 28 untyped type A, and 90 type B) and 274 deaths (149 H1N1, 104 H3N2, 9 untyped type A, and 12 type B). 

    The majority of severe cases are among those aged 65 and above (65.0%) and those with a history of chronic diseases (82.7%). 68.3% of those affected have not received the flu vaccine this season.

    According to data from the Taiwan Centers for Disease Control (CDC), the COVID-19 epidemic in Taiwan is declining, but it is still in its epidemic period. 

    In week 36 (September 6-12), there were 17,847 outpatient and emergency room visits related to COVID-19, a 13.3% decrease compared to the previous week (August 30-September 5). 

    Last week (September 8-14), there were 53 new severe cases and 18 local deaths. 

    Since October 2025, there have been a cumulative total of 675 locally transmitted cases of COVID-19 complicated by severe illness, of which 124 have died. 

    Severe cases are predominantly among those aged 65 and above (73.3%) and those with a history of chronic diseases (82.8%). 83.6% of these cases have not received the COVID-19 vaccine this season. 

    In the past four weeks, the most prevalent local variants have been NB.1.8.1 and PQ.16.1.1.

(...)

Source: 

Link: https://www.cdc.gov.tw/Bulletin/Detail/CqW5UAMFqpDkwJWfWG-WGw?typeid=9

____

Emergence and spread of NA-I223V and NA-S247N double-mutant #H1N1pdm09 #influenza viruses with reduced #oseltamivir susceptibility in the #Netherlands and beyond, 2023 to 2026

 

Abstract

In 2023/24, A(H1N1)pdm09 influenza viruses with neuraminidase (NA)-S247N emerged in NA-clade C.5.3.3 carrying NA-I223V, spread internationally, then faded. Such double mutants reappeared sporadically in 2024/25. They expanded again in 2025/26 in NA-clade D.3 viruses carrying NA-S247N after acquiring NA-I223V in Europe – notably Spain, the Netherlands, Finland and France, and beyond. Dutch double mutants from both seasons showed median 12- and 13-fold reduced inhibition by oseltamivir. These findings underscore the need for ongoing genomic and phenotypic monitoring of antiviral susceptibility.

© Creative Commons License. This work is licensed under a Creative Commons Attribution 4.0 International License.

Source: 

Link: https://doi.org/10.2807/1560-7917.ES.2026.31.36.2600733

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Updated #H1N1pdm09 #influenza virus #ferret infection #model permits refined #antiviral #assessment using aerosol inhalation challenge

 

Abstract

Seasonal influenza viruses continue to pose a significant threat to human health. As influenza viruses exhibit sustained genetic drift, it is imperative that animal studies utilize challenge strains that reflect contemporary, currently circulating viruses when evaluating pathogenicity, viral tropism, transmissibility, and antiviral sensitivity to better inform public health responses. Ferrets are considered the gold-standard small animal model for assessing currently circulating influenza viruses. Seasonal influenza A(H1N1)pdm09 viruses replicate well in both the upper and lower respiratory tract of ferrets, providing an important model for developing improved vaccination and therapeutic strategies; however, many of these studies have relied on a 2009 virus isolate. Utilising representative influenza A(H1N1)pdm09 virus strains from 2009 to 2022, we explored virus replication kinetics and lung pathogenesis in ferrets following intranasal inoculation with these contemporary strains. Our results revealed strain specific differences, with greater lung viral loads and pathogenesis following inoculation with A/Sydney/5/2021 compared to other strains. Efficient transmissibility of A/Sydney/5/2021 virus to naïve recipients was also observed following both contact and airborne exposure to infected donor ferrets. To refine this updated model, we performed side-by-side evaluation of oseltamivir antiviral efficacy following traditional intranasal or aerosol inhalation influenza challenges. Pre-treatment with oseltamivir demonstrated greater reductions in viral shedding from the upper respiratory tract than post-infection treatment of ferrets infected by aerosol inhalation, while the intranasal route showed reduced oseltamivir efficacy independent of the timing of antiviral treatment. These findings provide the basis for using an updated A(H1N1)pdm09 challenge virus for ferret studies as an alternative to the commonly used, but now less relevant 2009 early pandemic viruses. It also highlights how different methods of virus inoculation can influence outcomes of ferret antiviral studies, with an aerosol challenge model able to demonstrate differences between therapeutic and prophylactic treatments, which were not apparent with an intranasal challenge model.

Source: 

Link: https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014604

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#Taiwan, Seasonal #Influenza and #COVID19 Epidemics Weekly #Update (CDC, September 8 '26): H1N1pdm09 flu virus & SARS-CoV-2 PQ.16.1.1 variant are predominant

 

{Excerpts}

(...)

    The CDC pointed out that in week 35 (August 30th - September 5th), there were 115,136 outpatient and emergency room visits for influenza-like illnesses, an increase of 11.0% from the previous week, showing a recent upward trend. 

    The percentage of emergency room visits reached 11.2%, exceeding the epidemic threshold (11.0%), indicating the start of the epidemic period. 

    Additionally, last week (September 1st - September 7th), there were 105 new cases of severe influenza complications (97 H1N1, 4 H3N2, 4 untyped A cases) and 19 deaths (18 H1N1, 1 untyped A case). 

    Laboratory monitoring data shows that the influenza virus currently circulating in the community is mainly type A, with type A H1N1 accounting for 79.4% of the cases. 

    This flu season (2023-2024) has seen a cumulative total of 1,329 severe cases (717 H1N1, 498 H3N2, 24 untyped type A, and 90 type B) and 253 deaths (131 H1N1, 102 H3N2, 8 untyped type A, and 12 type B). 

    The majority of severe cases are among those aged 65 and above (65.1%) and those with a history of chronic diseases (82.8%). 68.6% of those affected have not received the flu vaccine this season.

    According to data from the Taiwan Centers for Disease Control (CDC), the COVID-19 epidemic in Taiwan is declining, but it is still in its epidemic period. 

    In week 35 (August 30 - September 5), there were 20,199 outpatient and emergency room visits related to COVID-19, a 9.7% decrease compared to the previous week (August 23 - August 29). 

    Last week (September 1 - September 7), there were 73 new severe cases and 15 deaths. 

    Since October 2025, there have been a cumulative total of 622 locally transmitted cases of COVID-19 complicated by severe illness, of which 106 have died. 

    The majority of severe cases are among those aged 65 and above (72.7%) and those with a history of chronic diseases (83.0%). 84.9% of these cases have not received the COVID-19 vaccine this season. 

    In the past four weeks, the predominant variant strain in locally transmitted cases has been PQ.16.1.1.

(...)

Source: 

Link: https://www.cdc.gov.tw/Bulletin/Detail/5gJTj70wu9L3psY5kQLUuA?typeid=9

____

#Report on #influenza viruses received and tested by the #Melbourne #WHO Collaborating Centre for Reference and Research on Influenza during 2025

 

Abstract

As part of its role in the World Health Organization (WHO) Global Influenza Surveillance and Response System (GISRS), the WHO Collaborating Centre for Reference and Research on Influenza in Melbourne (the Centre) received 13,817 human influenza-positive samples during 2025. Viruses were analysed for their antigenic, genetic, and antiviral susceptibility properties. Selected viruses were propagated in qualified cells or embryonated hens’ eggs for potential use in seasonal influenza virus vaccines. Of the 13,817 samples received or processed, influenza A(H1N1)pdm09 viruses predominated, accounting for 46.1% of samples, compared to 21.2% for A(H3N2) viruses and 19.5% for influenza B viruses; one influenza C virus was received. Among viruses analysed at the Centre, the majority of A(H1N1)pdm09 (> 99%) and influenza B (98%) viruses were antigenically similar to their respective WHO recommended vaccine strains for the Southern Hemisphere in 2025. In contrast, only 43% of A(H3N2) viruses were antigenically similar to their respective WHO recommended vaccine strains. Of 3,307 samples tested for susceptibility to the neuraminidase inhibitors oseltamivir and zanamivir, 37 A(H1N1)pdm09 viruses showed highly reduced inhibition by oseltamivir and no influenza viruses tested showed highly reduced inhibition by zanamivir. Of 5,080 samples with sequencing of the polymerase acidic (PA) gene, no genetic markers associated with highly reduced susceptibility to baloxavir marboxil were identified.

Source: 

Link: https://ojs.cdi.cdc.gov.au/index.php/cdi/article/view/3489

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#Taiwan, Seasonal #Influenza and #COVID19 Epidemics Situation #Update (CDC, September 1 '26): #H1N1pdm09 flu virus and PQ.16.1.1 SARS-CoV variant are predominant

 

{Excerpt}

(...)

    The CDC pointed out that in the 34th week (August 23-29), there were 101,628 outpatient and emergency room visits for influenza-like illnesses, an increase of 5.6% compared to the previous week, showing a recent slow upward trend. 

    In addition, last week (August 25-31), there were 85 new cases of severe influenza complications (80 H1N1, 3 H3N2, and 2 untyped A cases) and 14 deaths (12 H1N1, 1 H3N2, and 1 untyped A case). 

    Laboratory monitoring data shows that the influenza virus currently circulating in the community is mainly type A, with type A H1N1 accounting for 74.1% of the cases. 

    This flu season (2023-2024) has seen a cumulative total of 1,224 severe cases (620 H1N1, 494 H3N2, 20 untyped type A, and 90 type B) and 234 deaths (113 H1N1, 102 H3N2, 7 untyped type A, and 12 type B). 

    The majority of severe cases are among those aged 65 and above (64.6%) and those with a history of chronic diseases (82.8%). 69.4% of those affected have not received the flu vaccine this season.

    According to data from the Taiwan Centers for Disease Control (CDC), the COVID-19 epidemic in Taiwan is declining, but it remains at a plateau. 

    In the 34th week (August 23-29), there were 21,969 outpatient and emergency room visits related to COVID-19, a 13.4% decrease compared to the previous week (August 16-22). 

    Last week (August 25-31), there were 69 new locally transmitted severe cases and 18 local deaths. 

    Since October 2025, there have been a cumulative total of 549 locally transmitted cases of COVID-19 complicated by severe illness, of which 91 have died. 

    The majority of severe cases are among those aged 65 and above (72.5%) and those with a history of chronic diseases (83.1%). 85.1% of these cases have not received the COVID-19 vaccine this season. 

    In the past four weeks, the predominant variant strain in locally transmitted cases has been PQ.16.1.1.

(...)

Source: 

Link: https://www.cdc.gov.tw/Bulletin/Detail/GWRkQ03fZuKKWwdv191UyQ?typeid=9

____

#Antibody profiles across #H5N1 and previously circulating viruses are highly dynamic and #age- and imprint- independent

 

Abstract

The increasing incidence of H5N1 influenza virus transmission from animal species to humans has heightened concerns about an imminent H5N1 pandemic. Prior studies using recombinant hemagglutinin and neuraminidase proteins have reported age-dependent cross-reactivity to H5N1, attributed to immune imprinting from an individual's first influenza virus exposure. However, whether this pattern holds when using whole inactivated virus (WIV), capturing antibodies against diverse viral proteins, and is stable over time remains unknown. We therefore aimed to determine whether H5N1 cross-reactivity of pre-existing antibodies to whole virus follows an age-dependent or imprinting-specific pattern, and whether this pattern is stable over a five-year period. To this end, we measured serum antibody levels in adolescents, adults and seniors by ELISA using whole inactivated H5N1 virus as antigen rather than purified proteins. Detectable, albeit generally low, levels of H5N1-reactive antibodies were present in most individuals, irrespective of age. Comparison of antibody levels against H5N1 with those to five historical influenza virus strains revealed a consistent positive correlation between H5N1-reactive antibodies and responses to the H1N1pdm09 strain A/California/7/2009 (CA), across all age groups. Using unbiased clustering of antibody titers against H5N1, CA, and the H3N2 strain A/Perth/16/2009 (PE), we identified seven distinct age-transcending antibody profiles. These profiles covered individuals with varying titers to all three included viruses but also identified individuals with high anti-CA levels, yet low anti-H5N1 levels and vice versa. Moreover, despite stable antibody levels over a five-year interval in the study population, individual antibody levels and profiles fluctuated considerably over this period. Taken together, our results confirm the presence of H5N1-reactive antibodies in human sera and their association with previously circulating strains. However, they also caution against inferring antibody levels against a new strain based solely on responses to antigenically related strains and highlight the limitations of extrapolating immune status from single timepoint measurements.

Competing Interest Statement

The authors have declared no competing interest.

Source: 

Link: https://www.medrxiv.org/content/10.64898/2026.08.26.26361396v1

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#Influenza A virus #H5N1 genotypes #B3.13 and D1.1 show #temperature-dependent restriction of #replication in primary #human respiratory epithelial cell cultures derived from the upper and lower respiratory tract

 

Abstract

H5N1 clade 2.3.4.4b avian influenza A viruses pose a significant threat to wild animal populations, domesticated animals, and potentially, the human population. For H5N1s to infect and transmit among mammalian species, mutations for improved utilization of mammalian receptors and enhanced replication at the lower temperatures of the upper respiratory tract need to be acquired. A human H1N1pdm09-like virus was compared to H5N1 genotypes B3.13 and D1.1 for replication at 33ºC, 37ºC, and 39ºC – temperatures consistent with the upper and lower respiratory tract in humans, and dairy cow udder tissue. All H5N1 viruses had increased plaque sizes on MDCK cells at 37ºC and 39ºC compared to H1N1pdm09. In primary, differentiated human nasal and bronchial epithelial cultures, all H5N1 viruses show restricted infectious virus production compared to H1N1 at 33ºC. While H5N1 D1.1 also showed restricted replication at 37ºC and 39ºC, the H5N1 B3.13 replicated to nearly equivalent titers as H1N1pdm09. All H5N1 viruses demonstrated similar cell tropism in cells from the upper and lower respiratory tract, infecting more ciliated than non-ciliated cells relative to H1N1pdm09. H1N1, H5N1 B3.13 D1.1 infection induced similar innate immune factors, with nasal epithelial cells producing higher levels compared to bronchial epithelial cells. These data suggest that genotype B3.13 and D1.1 H5N1 viruses show different temperature dependent replication patterns compared to H1N1pdm09.

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.08.27.747488v1

____

#Global Respiratory #Virus #Activity: Weekly #Update (WHO, August 28 '26)

 

{Excerpt, from Weekly Epidemiological Record}

(...)

    The findings below are based on surveillance conducted through the WHO Global Influenza Surveillance and Response System (GISRS). 

    More details can be found on the Global Influenza Programme's surveillance and monitoring page.

Overview

    ° In week 33 2026, influenza positivity was below 10% and SARS-CoV-2 activity remained low globally. 

    ° During the past few weeks, influenza positivity remained just below 10% overall in the tropical areas and southern hemisphere temperate and subtropical areas. 

    ° RSV positivity also remained low globally.

Influenza

    ° Globally, influenza detections remained low in week 33 with influenza A and B viruses detected in similar proportions.

    ° In the southern hemisphere, influenza percent positivity was elevated (>10%) in one country in Temperate South America. 

    ° Percent positivity was over 30% in one country in Oceania where a medium increase in activity was observed.

    ° In the northern hemisphere, influenza percent positivity was elevated (>10%) in some countries in Central America and the Caribbean, Tropical South America, Western Africa, Western, Southern and South-East Asia and in single countries in Middle Africa, South West and Northern Europe and Eastern Asia. 

    ° Percent positivity was over 30% in single countries in Tropical South America, Western and Eastern Africa and Southern Asia. 

    ° Increases in activity were observed in some countries in Central America and the Caribbean and Southern Asia and in single countries in Tropical South America, Western, Eastern and Middle Africa, South West Europe and Western Asia.

    ° In the zones with elevated positivity, influenza A(H3N2) was predominant in South West Europe, Eastern Africa, Eastern Asia and Oceania; influenza A(H1N1)pdm09 was predominant in Western, Southern and South-East Asia and influenza B was predominant in Tropical and Temperate South America. 

    ° Influenza A and B were codominant in Central America and the Caribbean and Western Africa and influenza A(H1N1)pdm09 and influenza A(H3N2) were codominant in Middle Africa.

SARS-CoV-2

    ° Globally, SARS-CoV-2 positivity remained stable and low across most reporting countries, with elevated positivity (>10%) reported in countries in Central America and the Caribbean and in single countries in Tropical South America, Southern and South-East Asia. 

    ° Small increases in activity were observed in countries in Central America and the Caribbean, Northern Europe and in a single country in Southern Asia.

Respiratory Syncytial Virus (RSV)

    ° RSV positivity was elevated (>10%) in a few countries in Central America and the Caribbean, Tropical and Temperate South America and in a single country in Southern Asia. 

    ° Percent positivity was over 30% in a single country in Temperate South America. 

    ° Small increases in activity were observed in two countries in Central America and the Caribbean. 

    ° RSV and influenza activity were both elevated in single countries in Temperate South America and Southern Asia.

Severity assessment

    ° The severity assessments here are reported from countries, areas and territories. 

    ° Assessments for transmissibility can be reported based on syndromic parameters and/or influenza-specific parameters. 

    ° In the southern hemisphere temperate and subtropical areas, influenza-specific transmissibility was reported as low (1) and moderate (1); transmissibility using syndromic data was reported as moderate (1). 

    ° In the northern hemisphere temperate and subtropical areas, influenza-specific transmissibility was reported as below seasonal threshold (11) and low (2); transmissibility using syndromic data was reported as below seasonal threshold (8). 

    ° Influenza-specific transmissibility was reported as moderate in one country in the tropical areas.

Current update: Global Respiratory Virus Activity: Weekly Update N° 592

All past updates: Global respiratory virus updates

(...)

Source: 

Link: https://www.who.int/publications/journals/weekly-epidemiological-record/wer101-34

____

#Taiwan, #Epidemics of Respiratory Viruses (#COVID19, #Influenza, #Enteroviruses) Weekly Update (CDC, August 25 '26): PQ.16.1.1 Variant Still Predominant

 

{Excerpts}

(...)

    CDC monitoring data shows that the domestic COVID-19 epidemic is at a plateau. 

    In week 33 (August 16-22), there were 24,995 outpatient and emergency room visits for COVID-19, a 6.0% decrease compared to the previous week (August 9-15). 

    Last week (August 18-24), there were 59 new locally transmitted severe cases and 19 new locally transmitted deaths. 

    Since October 2025, there have been a total of 480 local cases of COVID-19 complicated by severe illness, of which 73 have died. 

    The majority of severe cases are among those aged 65 and above (73.5%) and those with a history of chronic diseases (82.5%). 86.5% of these cases have not been vaccinated this season. 

    In the past four weeks, the predominant variant strain in local cases has been PQ.16.1.1.     

    As of August 24, approximately 1.823 million doses of the COVID-19 vaccine have been administered this season. There are currently about 111,000 doses remaining nationwide, which will be available until September 9. Eligible and needy individuals are advised to take advantage of this time and get vaccinated as soon as possible.

    Regarding the influenza epidemic, in week 33 (August 16-22), there were 94,340 outpatient and emergency room visits for influenza-like illnesses, a slight decrease of 2.5% compared to the previous week. 

    Additionally, last week (August 18-24), there were 64 new cases of severe influenza complications (59 H1N1 and 5 H3N2) and 15 deaths (all H1N1). 

    Laboratory surveillance data shows that the influenza virus currently circulating in the community is predominantly type A, with type A H1N1 accounting for a high percentage at 69.7%. 

    This flu season (2014-2015) saw a cumulative total of 1,139 severe cases (540 H1N1, 491 H3N2, 18 untyped A, and 90 B) and 220 deaths (101 H1N1, 101 H3N2, 6 untyped A, and 12 B). 

    The majority of severe cases were among those aged 65 and over (63.8%) and those with a history of chronic illness (82.4%). 71.0% of patients had not received the flu vaccine this season.

    Regarding enterovirus cases, in week 33 (August 16-22), there were 6,546 outpatient and emergency room visits, similar to the previous week (6,646), indicating a stable recent trend. 

    Laboratory surveillance over the past four weeks showed that Coxsackievirus A6 was the most prevalent enterovirus in the community, followed by enterovirus D68 and Coxsackievirus A16. 

    This year (2026), there have been a total of 6 confirmed cases of enterovirus infection complicated with severe illness (including 1 death), including 4 cases of enterovirus D68, 1 case each of Coxsackievirus A4 and Coxsackievirus A16. 

    Regarding the dengue fever outbreak, as of August 24th this year, there have been a total of 134 confirmed dengue fever cases, including 7 local cases (all residing in Kaohsiung City) and 127 imported cases. The imported cases were mainly from Southeast Asian and South Asian countries such as Indonesia (26 cases), Vietnam (26 cases), and the Maldives (16 cases). The cumulative number of cases is lower than the same period in 2025 (152 cases).

(...)

Source: 

Link: https://www.cdc.gov.tw/Bulletin/Detail/QiAsLBvifNAj7FJzGc-ApQ?typeid=9

____

Detection and characterization of #antiviral #resistant viruses during the #influenza season of 2024–25

 

ABSTRACT

During the high severity season of 2024–25, CDC with public health partners sequenced and analyzed genomes of >10,000 influenza viruses for antiviral resistance markers. Available sequence-flagged and representative viruses were tested with antivirals using in vitro assays. In the US, three oseltamivir-resistant A(H3N2) viruses had treatment-emergent neuraminidase (NA) mutations, either E119V or R292K. Oseltamivir-resistant A(H1N1)pdm09 viruses with NA-H275Y were detected in 15 states, albeit at a low frequency (0.53%). They belonged to several phylogenetic groups, with hemagglutinin (HA) subclade D.3.1 combined with either NA subclade D.1 or D.2 being most common. Based on shared sequence data, nearly all H275Y viruses from Australia, Canada, and Chile also belonged to these HA and NA subclades. Conversely, most H275Y viruses (68/81) from China belonged to HA subclade C.1.9 and NA subclade D and shared the permissive mutation R257K. Influenza polymerase acidic (PA) mutations conferring 4- to 92-fold decreased baloxavir susceptibility were detected in nine influenza A viruses. Viruses with PA-I38T showed mild attenuation of replicative fitness in three cell lines. Based on available data, NA-H275Y and PA-I38T viruses were collected from patients with no exposure to antivirals. Baseline susceptibility to all US-approved influenza antivirals remained largely unchanged compared to previous seasons. All swine-origin viruses detected in the US had adamantane resistance-conferring marker, M2-S31N, but remained susceptible to other approved antivirals. Monitoring antiviral susceptibility has substantially improved with increased sequencing capacities and bioinformatic support at public health laboratories. Information gained through influenza surveillance has been used to guide recommendations on antiviral use.

Source: 

Link: https://journals.asm.org/doi/10.1128/spectrum.01514-26

____

#Assessment of #influenza virus and #coronavirus #tropism, #replication competence and disease severity in ex vivo and in vitro cultures of the #human respiratory tract

ABSTRACT

The emergence of animal influenza viruses circulating in poultry and human populations poses a significant public health threat, yet current risk assessment tools that connect surveillance data to human transmission risk and disease severity are lacking. To address this, we employed a semi-quantitative approach to analyze virus tropism and replication competence, conducting risk assessments of influenza and coronavirus adaptation to human transmission in an ex vivo model, and evaluating virus-induced impairment of alveolar fluid clearance (AFC) in vitro as a correlation of disease severity. Our results showed that seasonal influenza A H1N1, H3N2, influenza B, MERS-CoV, and SARS-CoV exhibited productive viral replication and tissue infection in bronchial tissues, whereas wild bird surveillance isolates such as H5N3 and H7N1 showed minimal replication when compared to pandemic H1N1 and highly pathogenic avian influenza (HPAI) H5N1. Notably, differential lung viral replication and tissue tropism were detected for H5N6 and H9N2. HPAI H5N1, H7N9, MERS-CoV, and SARS-CoV caused more severe AFC impairment than seasonal H1N1, H3N2, and influenza B viruses, correlating with their clinical severity. Overall, these findings revealed an important association between viral tropism and human transmissibility in ex vivo explants, as well as the impairment of AFC in vitro, which aligns with the clinical manifestations of disease severity across different viral strains.

Source: 

Link: https://www.microbiologyresearch.org/content/journal/jgv/10.1099/jgv.0.002281

____

#Genetic and biological characterization of a #reassortant #H3N2 swine #influenza virus isolated in #China with internal genes from the 2009 pandemic #H1N1

 

Abstract

Swine influenza virus (SIV) not only causes significant losses to the pig industry but also poses a potential threat to human health due to its ability for cross-species transmission and zoonotic characteristics. In this study, 600 nasal swab samples were collected from pigs in Shandong Province and tested for SIV using RT-qPCR. One sample tested positive, and the virus was successfully isolated in 10-day-old specific-pathogen-free (SPF) embryonated chicken eggs. Subtype-specific RT-PCR and sequencing identified the isolate as H3N2, designated A/swine/Shandong/116/2022 (H3N2). Whole-genome sequencing and similarity analysis showed that PB2, PB1, PA, NP, and M genes were most similar to H1N1 viruses (97.71–99.67%), while HA, NA, and NS genes were closest to H3N2 viruses (96.06–97.85%), suggesting this isolate is a reassortant between H1N1 and H3N2 viruses. Phylogenetic analysis indicated that PB2, PB1, PA, NP, and M genes belong to the 2009 pandemic H1N1 (pdm/09 H1N1) lineage, HA and NA genes belong to the human-like H3N2 (HL H3N2) lineage, and the NS gene belongs to the triple-reassortant (TR) H1N2 lineage. Key amino acid analysis showed a monobasic HA cleavage site (PEKQTR/G), consistent with low pathogenicity, and residues 190V, 226I, and 228S, which may affect receptor binding. PB2 residues 271A, 590S, and 591R may influence viral replication and host adaptation. Compared with the human influenza vaccine strain A/Darwin/9/2021 (H3N2), several amino acid changes were found in HA antigenic sites A, B, C, and E, suggesting possible antigenic drift. In addition, clear differences were found in N-linked glycosylation sites between the isolate and vaccine strain, including loss of several glycosylation sites and the appearance of a new site at position 499, which may change virus antigenicity and immune recognition. Functional studies demonstrated that the isolate efficiently infected MDCK cells and replicated in the respiratory tissues of BALB/c mice, causing mild to moderate lung lesions without mortality or significant weight loss. In summary, the isolated is a multi-source reassortant virus with low pathogenicity, providing valuable insights into the genetic characteristics and epidemiology of H3N2 SIV circulating in pigs in China.

Source: 

Link: https://link.springer.com/article/10.1186/s12866-026-05324-w

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#Antibodies against #influenza #H1N1pdm2009 and B/Victoria strains but not #H3N2 are increased in recent onset type 1 #narcolepsy versus matched controls

 

Abstract

Study Objectives: 

Onsets of Narcolepsy type-1 (NT1) increased following A/H1N1 vaccination with PandemrixTM in Europe and with A/H1N1pdm2009 infections in China and other countries. To test if other strains could trigger narcolepsy, we measured strain-specific antibodies in patients with recent onset NT1 compared to controls. 

Methods: 

Antibodies against hemagglutinin (HA) and neuraminidase (NA) were tested in 62 patients with very recent onset (onset and blood collection following a single flu season, mean +/- SEM: 0.44 +/- 0.06 years since onset) and 100 controls matched by age, sex, season and year of collection (2000-2025). Results were next extended to 181 recent onset patients (mean +/- SEM: 1.00 +/- 0.05 years) versus 260 controls, matched by sex, season and year, but having a slightly higher mean age. HA inhibition (HAI) and NA inhibition (NAI) assays were conducted using flu strains known to circulate during the corresponding flu seasons. HAI results are shown as % positive (titers >= 40) and NAI results as geometric mean titers. Odds ratio (OR) and coefficient were used to compare antibody titers in NT1 versus controls. The contribution of each assay to prediction was finally quantified in the larger sample set using Shapley decomposition. 

Results: 

NT1 patients had increased anti-HA and anti-NA antibodies against A/H1N1pdm2009 (anti-HA OR = 3.86, anti-NA coefficient = 0.35) and B/Victoria (anti-HA OR =1.90, anti-NA coefficient = 0.22), but not A/H1N1pre2009, A/H3N2, or B/Yamagata, independent of HLA-DQB1*06:02 status, age, sex, and flu season. Correlations between anti-HA and anti-NA antibodies titers were weak to moderate but significant (r2=-0.10 to 0.34). Multivariable model outperformed age-only baseline (McFadden R2 = 0.19 vs. 0.03; AUC = 0.79 vs. 0.64; likelihood-ratio test X2 = 51, p<0.001), with anti-HA against A/H1N1pdm2009 (coefficient = 0.78, p < 0.001) and anti-NA against B/Victoria (coefficient = 0.69, p < 0.001) emerging as the strongest independent predictors. 

Conclusions: 

A/H1N1pdm2009 and B/Victoria, but not other strains can trigger the autoimmune process leading to orexin cell loss in narcolepsy.

Competing Interest Statement

The authors have declared no competing interest.

Source: 

Link: https://www.medrxiv.org/content/10.64898/2026.06.13.26355596v1

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#Genomic #wastewater #surveillance of seasonal and #zoonotic #influenza A viruses in #California during the 2024-2025 flu season

 

Abstract

Wastewater genomic surveillance provides an opportunity to detect human and animal influenza A virus (IAV). We aimed to implement an IAV genomic surveillance framework agnostic to subtype, which enables recovery of IAV from multiple hosts and estimation of proportions across subtypes. We conducted IAV genomic surveillance in wastewater during the 2024-2025 flu season at multiple sites in California and compared these data with available human clinical IAV sequences and test positivity. We applied a custom whole-genome, multi-host IAV probe enrichment panel and adapted our custom expectation-maximization (EM) algorithm to deconvolute IAV mixtures in wastewater and infer subtype relative abundances. Absolute IAV concentrations were quantified using RT-PCR-based assays. H5N1 wastewater and clinical sequences were further characterized by constructing a whole-genome maximum-likelihood phylogenetic tree. Finally, we performed variant analysis to examine amino acid substitutions detected in wastewater. Our IAV probe enrichment method and EM algorithm successfully enriched all eight segments of three circulating IAV subtypes and accurately estimated subclade relative abundances for mixed IAV samples. Seasonal human H1N1pdm09 and H3N2 were detected throughout the study period from both wastewater and clinical sequencing data, with H1N1 subclades 6B.1A.5a.2a.1 and 6B.1A.5a.2a co-circulating, and H3N2 dominated by subclade 3C.2a1b.2a.2a.3a.1. Wastewater surveillance consistently detected H5N1 clade 2.3.4.4b across three monitored wastewater sites, while clinical H5N1 detections, from anywhere in CA, were sporadic and rare. Whole-genome phylogenetic analysis revealed that wastewater H5N1 sequences clustered with reference sequences associated with dairy cow and avian infections, while all human clinical H5N1 sequences clustered exclusively with reference sequences associated with dairy cow infections. Amino acid substitutions were identified across viral segments, and no mutations associated with mammalian adaptation were observed from wastewater samples.

Competing Interest Statement

The authors have declared no competing interest.

Source: 

Link: https://www.medrxiv.org/content/10.64898/2026.06.10.26355323v1

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Increased burden of #influenza #H1N1pdm09 in older adults following the #COVID19 #pandemic

 

Abstract

Of the two influenza A virus (IAV) subtypes circulating endemically in humans, A/H3N2 and A/H1N1pdm09, A/H3N2 has historically been the dominant driver of disease burden in older adults. Based on an analysis of publicly available global surveillance data from 2015 to 2025 (>300,000 subtyped, age-stratified infections), we report a substantially increased contribution of A/H1N1pdm09 to influenza morbidity in older adults since approximately 2022. Birth cohort-stratified analyses suggest elevated A/H1N1pdm09 burden among individuals born before 1955-1959, consistent with erosion of pre-existing immunity originally generated by exposure to historical A/H1N1 strains. Pooled estimates across datasets and analytical approaches indicate the increase in A/H1N1pdm09 burden rises with earlier birth year, ranging from 1.22-fold (95% CI 1.08-1.37) for the 1955-1959 birth cohort to 3.10-fold (95% CI 2.58-3.72) for the 1930-1934 cohort. These findings point to a substantial rise in the overall influenza burden among the most vulnerable age groups, with implications for vaccine policy, clinical management, and public health planning.

Competing Interest Statement

C.A.R. has received consulting fees from CSL Seqirus, Moderna, Pfizer, GSK, and Sanofi for advisory services unrelated to this work.

Source: 

Link: https://www.medrxiv.org/content/10.64898/2026.05.20.26353664v1

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#Zoonotic #infections and genomic #evolution associated with novel #reassortants swine-origin #influenza A viruses in #Spain

 

Abstract

Influenza A virus (IAV) circulates widely in European pig populations and continues to diversify through frequent introductions from humans, followed by reassortment within swine. Spain represents a particularly dynamic ecological setting due to the coexistence of intensive white pig production, extensive Iberian pig systems, and abundant wild boar populations. This study provides an integrated analysis of IAV evolution and genomic diversity in swine in Spain between 2019 and 2022, expanding on previous surveillance from 2016 to 2019. Sampling across 24 provinces yielded 66 new whole genome sequences from Iberian and white pigs. We identified 18 genotypes, including 11 novel reassortants not detected in our previous survey. Several genotypes, such as H1huN2 G21 and G22, H3N2 G23, and the unusual H3N1 G12, were exclusive to the country. Some genotypes were detected across white pigs, Iberian pigs, and wild boar in Toledo and Badajoz, suggesting viral flow among swine populations. Phylogenetic analyses revealed ongoing introductions of H1N1pdm09 from humans into pigs, generating at least five reassortant genotypes (G10, G16 to G19). These lineages incorporated pandemic internal cassettes and, in some cases, human seasonal N2 segments, highlighting the continued role of humans as a source of viral incursions. Conversely, four zoonotic infections (H1N1v) detected in Spain between 2022 and 2026 were linked to genotypes circulating in white pigs, underscoring the bidirectional nature of IAV transmission at the human swine interface. Overall, this study demonstrates that Spain provides ecological conditions conducive to IAV diversification, reassortment, and zoonotic risk. The findings reinforce the need for sustained One Health surveillance.

Competing Interest Statement

The A.G.-S. laboratory has received research support from Avimex, Dynavax, Pharmamar, and Accurius, outside of the reported work within the last three years. A.G.-S. has consulting agreements for the following companies involving cash and/or stock within the last three years: Castlevax, Amovir, Vivaldi Biosciences, Contrafect, Avimex, Pagoda, Accurius, Applied Biological Laboratories, Pharmamar, CureLab Oncology, CureLab Veterinary, Virofend and Prosetta, outside of the reported work. A.G.-S. has been an invited speaker in meeting events within the last three years organized by Seqirus, Novavax and Hipra. A.G.-S. is inventor on patents and patent applications on the use of antivirals and vaccines for the treatment and prevention of virus infections and cancer, owned by the Icahn School of Medicine at Mount Sinai, New York, outside of the reported work. The rest of the authors report no conflicts of interest.

Funder Information Declared

Centre for Research on Influenza Pathogenesis and Transmission (CRIPT), one of the National Institute of Allergy and Infectious Diseases (NIAID) funded Centres of Excellence for Influenza Research and Response (CEIRR), contract #75N93021C00014

Intramural Research Program of the National Library of Medicine at the US National Institutes of Health

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.05.22.724525v1

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Cross-reactive #human #antibody responses to #H5N1 #influenza virus #neuraminidase are shaped by immune history

 

Abstract

H5N1 highly pathogenic avian influenza viruses have spread globally and pose a pandemic risk. Prior studies suggest that early life exposures to group 1 influenza viruses (H1N1 and H2N2) prime antibodies that cross-react to the hemagglutinin of H5N1, which is also a group 1 virus. However, less is known about how immune history affects antibody responses against the H5N1 neuraminidase (NA). We measured NA inhibition antibodies against multiple H5N1 viruses using sera from 155 individuals born between 1927 and 2016. Individuals likely primed in childhood with H1N1 viruses possessed higher levels of antibodies that cross-react with the NA of H5N1 viruses compared to those primed with H2N2 or H3N2 viruses. While young children rarely possessed cross-reactive N1 antibodies, childhood infections with contemporary H1N1, but not H3N2, viruses elicited them. We also measured antibodies against an H5N5 virus (A6 genotype) that recently caused a fatal infection in the United States. Consistent with the lack of circulation of N5 viruses in humans, we found low levels of antibodies against the N5 NA. Our data suggest that immune history greatly impacts the generation of cross-reactive NA antibodies, and that reassortment with other NAs may increase the risk of H5 infection of humans.

Source: 

Link: https://www.nature.com/articles/s41467-026-72941-4

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Historical #Pandemic and Contemporary #Influenza A Viruses Reveal #PB2 M631L as a Convergent #Adaptation to #Human ANP32

 

Abstract

Understanding the genetic changes that allow avian influenza A viruses (IAVs) to switch their natural hosts and establish productive infection in humans is important for pandemic risk assessment. Adaptations in the IAV polymerase are required to overcome species-specific restrictions imposed by host ANP32 proteins. Notably, avian virus polymerase is generally only poorly supported by human ANP32 proteins due to species-specific differences. Consequently, efficient polymerase adaptation to the binding interface of human ANP32 requires distinct amino acid changes, such as PB2 E627K. A separate adaptation, PB2 M631L, has recently been reported in mammalian-adapted IAV; however, its functional role across divergent viral lineages and its relationship to host ANP32-dependent adaptation remain incompletely defined. Here, we examine PB2 M631L in the polymerases of a 1918 pandemic strain, a recombinant contemporary H1N1pdm09, and a recent clade 2.3.4.4b H5N1 virus. Using polymerase activity and protein-interaction assays, we show that PB2 M631L enhances polymerase activity and ANP32 binding in human—but not avian—contexts, and that this effect is conserved across multiple viral backgrounds. In H1N1pdm09, PB2 M631L also increased virus replication in mammalian cells. These findings indicate that PB2 M631L contributes to enhanced polymerase compatibility with human ANP32 proteins and are consistent with a role in adaptation across multiple influenza virus lineages. Our results highlight how analysis of historical pandemic strains can inform risk assessment for future emerging viruses.

Source: 

Link: https://www.mdpi.com/2076-2607/14/4/859

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