# Influenza at #human - #animal #interface - Summary and #risk #assessment, from 13 June to 7 July 2026 (WHO): 1 new case of #H5 virus, 2 of #H9N2 and one of #H3N2v

 

Influenza at the human-animal interface - Summary and risk assessment, from 13 June to 7 July 2026 {1} 

    • New human cases {2}: 

        ° From 13 June to 7 July 2026, based on reporting date, detections of influenza A(H5) in one human, influenza A(H9N2) in two humans, and an influenza A(H3N2) variant ((H3N2)v) virus in one human were officially reported. 

    • Circulation of influenza viruses with zoonotic potential in animals: 

        ° High pathogenicity avian influenza (HPAI) events in poultry and non-poultry animal species continue to be reported to the World Organisation for Animal Health (WOAH).{3} 

        ° The Food and Agriculture Organization of the United Nations (FAO) also provides a global update on avian influenza viruses with pandemic potential.{4} 

        ° Additionally, low pathogenicity avian influenza viruses as well as swine influenza viruses continue to circulate in animal populations. 

    • Risk assessment {5}: 

        ° There have been no reports of sustained human-to-human transmission associated with the above-mentioned human infection events. 

        ° Based on information available at the time of this risk assessment update, the overall public health risk from currently known influenza A viruses detected at the human-animal interface has not changed and - At present, these viruses are not thought to be capable of sustained human-to-human transmission, although this could change as they evolve. 

        ° Although human infections with viruses of animal origin are infrequent, they are not unexpected at the human-animal interface.  

    • IHR compliance {6}: 

        ° This includes any influenza A virus that has demonstrated the capacity to infect a human and its haemagglutinin (HA) gene (or protein) is not a mutated form of those, i.e. A(H1) or A(H3), circulating widely in the human population. 

        ° Information from these notifications is critical to inform risk assessments for influenza at the human-animal interface.  

Avian influenza viruses in humans 

A(H5), Bangladesh   

    ° On 15 June 2026, Bangladesh notified WHO of one laboratory-confirmed human case of avian influenza A(H5) infection in Bangladesh in a child from Sylhet Division. 

    ° The case was detected notified through the National Influenza Surveillance, Bangladesh (NISB) platform as an influenza likeillness (ILI) case.    

    ° The patient developed respiratory symptoms on 17 May 2026, received outpatient healthcare on 20 May. 

    ° A clinical sample was collected that day and was received by the Institute of Epidemiology, Disease Control and Research (IEDCR) on 4 June as part of routine surveillance. 

    ° The sample tested positive for influenza A(H5) virus by real-time reverse transcription polymerase chain reaction (RTPCR) on 11 June.    

    ° The patient is now in good health and reported no travel history and no history of exposure to poultry. 

    ° However, poultry deaths were reported in the area surrounding the patient’s residence. 

    ° The outbreak investigation team identified and followed close and possible contacts. 

    ° Samples from some of the close contacts as well as animal and environmental samples were collected for testing for influenza. 

    ° All contacts remained asymptomatic and all samples tested negative for influenza.    

    ° This is the third laboratory-confirmed human case of avian influenza A(H5) reported in Bangladesh in 2026, and the 15th human case of avian influenza A(H5) reported to WHO from Bangladesh since 2008, including two fatal cases, one reported in 2013 and one in 2026.  

Risk assessment for avian influenza A(H5) viruses:

1. What is the current global public health risk of additional human cases of infection with avian influenza A(H5) viruses?    
• Most human infections so far have been reported in people exposed to A(H5) viruses, for example, through contact with infected poultry or contaminated environments, including live poultry markets, and occasionally infected mammals and contaminated environments. 
• As long as the viruses continue to be detected in animals and related environments humans are exposed to, further human cases associated with such exposures are expected but remain unusual. 
• The impact for public health if additional sporadic cases are detected is minimal. 
• The current overall global public health risk is low.  
2. What is the likelihood of sustained human-to-human transmission of avian influenza A(H5) viruses related to the events above?    
• No sustained human-to-human transmission  has  been identified associated with the recent reported human infections with avian influenza A(H5) viruses.
•  There has been no reported human-to-human transmission of A(H5N1) viruses since 2007, although there may be gaps in investigations.
•  In 2007 and the years prior, small clusters of A(H5) virus infections in humans were reported, including some involving health care workers, where limited human-to-human transmission could not be excluded; however, sustained human-to-human transmission was not reported.
•  Current evidence suggests that influenza A(H5) viruses related to these events did not acquire the ability to efficiently transmit between people.    
3. What is the likelihood of international spread of avian influenza A(H5) viruses by travellers?    
• Should infected individuals from affected areas travel internationally, their infection may be detected in another country during travel or after arrival. 
• If this were to occur, further communitylevel spread is considered unlikely as current evidence suggests these viruses have not acquired the ability to transmit easily among humans.    

A(H9N2), China  

    ° Between 12 and 23 June 2026, two laboratory-confirmed cases of A(H9N2) virus infection were detected in China. 

    ° Both cases had mild illness and were hospitalized in isolation wards at the time of reporting. 

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    ° Both cases had exposure to local live bird markets. 

    ° Samples from environments associated with the likely area of exposure of the cases tested positive for A(H9) viruses. 

    ° No further cases were detected among contacts of these cases.   

Risk assessment for avian influenza A(H9N2):  

1. What is the global public health risk of additional human cases of infection with avian influenza A(H9N2) viruses?  
• Most human cases follow exposure to the A(H9N2) virus through contact with infected poultry or contaminated environments. 
• Most human infections of A(H9N2) to date have resulted in mild clinical illness. 
• Since the virus is endemic in poultry in multiple countries in Africa and Asia, additional human cases associated with exposure to infected poultry or contaminated environments are expected but remain unusual. 
• The impact to public health if additional sporadic cases are detected is minimal. 
• The overall global public health risk is low.  
2. What is the likelihood of sustained human-to-human transmission of avian influenza A(H9N2) viruses related to these events?  
• At the present time, no sustained human-to-human transmission has been identified associated with the recently reported human infections with A(H9N2) viruses. 
• Current evidence suggests that A(H9N2) viruses from these cases did not acquire the ability of sustained transmission among humans.  
3. What is the likelihood of international spread of avian influenza A(H9N2) virus by travellers?  
• Should infected individuals from affected areas travel internationally, their infection may be detected in another country during travel or after arrival. 
• If this were to occur, further community level spread is considered unlikely as current evidence suggests the A(H9N2) virus subtype has not acquired the ability to transmit easily among humans.  

Swine influenza viruses in humans 

Influenza A(H3N2)v, Brazil  

    ° On 25 June 2026, Brazil notified PAHO/WHO of a laboratory-confirmed human infection with an influenza A(H3N2)v virus detected in a child in Santa Catarina state. 

    ° The patient had symptom onset on 12 June 2026 and due to worsening respiratory symptoms, healthcare was sought on 16 June. 

    ° The patient was referred for hospital admission with a diagnosis of Severe Acute Respiratory Infection (SARI). 

    ° Upon admission, an antigen test confirmed influenza A and the patient was placed in a private respiratory isolation room and antiviral treatment was initiated. 

    ° The patient was discharged on 19 June.  

    ° A nasopharyngeal swab sample was collected on 16 June and sent to the State public health laboratory for real-time RT-PCR. 

    ° On 18 June, a swine-origin influenza H3 variant was suspected, and the sample was sent to the Laboratory of Respiratory Viruses, Exanthems, Enteroviruses, and Viral Emergencies (LVRE) at the Oswaldo Cruz Institute (Fiocruz/Rio de Janeiro) on 19 June. 

    ° Analyses confirmed the presence of an influenza A(H3N2)v virus via molecular testing and genomic sequencing. 

    ° An investigation by the state and municipality epidemiological surveillance team found that all contacts were asymptomatic before, during and after the child’s illness. 

    ° The child's grandfather worked at a swine nursery housing approximately 5,000 animals, though he noted that sanitary barriers were in place. 

    ° The child frequently visited the grandfather's home and had contact with him several days a week.  

    ° This is the first human A(H3N2)v infection detected in the Brazil in 2026 and the first case reported in the state of Santa Catarina. 

Risk assessment for swine influenza viruses:    

1. What is the public health risk of additional human cases of infection with swine influenza viruses?    
• Swine influenza viruses circulate in swine populations in many regions of the world. 
• Depending on geographic location, the genetic characteristics of these viruses differ. 
• Most human cases are exposed to swine influenza viruses through contact with infected animals or contaminated environments. 
• Human infection tends to result in mild clinical illness in most cases. 
• Since these viruses continue to be detected in swine populations, further human cases are expected.
•  The impact to public health if additional sporadic cases are detected is minimal. 
• The overall risk of additional sporadic human cases is low.    
2. What is the likelihood of sustained human-to-human transmission of swine influenza viruses?     
• No sustained human-to-human transmission was identified associated with the event described above. 
• Current evidence suggests that contemporary swine influenza viruses have not acquired the ability of sustained transmission among humans.   
3. What is the likelihood of international spread of swine influenza viruses by travellers?     
• Should infected individuals from affected areas travel internationally, their infection may be detected in another country during travel or after arrival. 
• If this were to occur, further community level spread is considered unlikely as current evidence suggests that these viruses have not acquired the ability to transmit easily among humans.   

Overall risk management recommendations: 

    ° Surveillance and investigations 

        • Due to the constantly evolving nature of influenza viruses, WHO continues to stress the importance of global strategic surveillance in animals and humans to detect virologic, epidemiologic and clinical changes associated with circulating influenza viruses that may affect human (or animal) health. 

            Continued vigilance is needed within affected and neighbouring areas to detect infections in animals and humans. 

            Close collaboration with the animal health and environment sectors is essential to understand the extent of the risk of human exposure and to prevent and control the spread of animal influenza. 

            WHO has published guidance on surveillance for human infections with avian influenza A(H5) viruses. 

        • As the extent of influenza virus circulation in animals is not clear, epidemiologic and virologic surveillance and the follow-up of suspected human cases should continue systematically. 

            Guidance on investigation of non-seasonal influenza and other emerging acute respiratory diseases has been published on the WHO website. 

        • Countries should: 

            - increase avian influenza surveillance in domestic and wild birds, 

            - enhance surveillance for early detection in cattle populations in countries where HPAI is known to be circulating, include HPAI as a differential diagnosis in non-avian species, including cattle and other livestock populations, with high risk of exposure to HPAI viruses; 

            - monitor and investigate cases in non-avian species, including livestock, 

            - report cases of HPAI in all animal species, including unusual hosts, to WOAH and other international organizations, 

            - share genetic sequences of avian influenza viruses in publicly available databases, 

            - implement preventive and early response measures to break the HPAI transmission cycle among animals through movement restrictions of infected livestock holdings and strict biosecurity measures in all holdings, 

            - employ good production and hygiene practices when handing animal products, and protect persons in contact with suspected/infected animals.{7} 

            - More guidance can be found from WOAH and FAO. 

        • When there has been human exposure to a known outbreak of an influenza A virus in domestic poultry, wild birds or other animals – or when there has been an identified human case of infection with such a virus – enhanced surveillance in potentially exposed human populations becomes necessary. 

            - Enhanced surveillance should consider the health care seeking behaviour of the population, and could include a range of active and passive health care and/or communitybased approaches, including: enhanced surveillance in local influenza-like illness (ILI)/SARI systems, active screening in hospitals and of groups that may be at higher occupational risk of exposure, and inclusion of other sources such as traditional healers, private practitioners and private diagnostic laboratories. 

        • Vigilance for the emergence of novel influenza viruses with pandemic potential should be maintained at all times including during a non-influenza emergency. In the context of the cocirculation of SARS-CoV-2 and influenza viruses, WHO has updated and published practical guidance for integrated surveillance. 

    ° Notifying WHO 

        • All human infections caused by a new subtype of influenza virus are notifiable under the International Health Regulations (IHR, 2005).{8,9} State Parties to the IHR (2005) are required to immediately notify WHO of any laboratory-confirmed {10} case of a recent human infection caused by an influenza A virus with the potential to cause a pandemic {11}. Evidence of illness is not required for this report. Evidence of illness is not required for this report. 

        • WHO published the case definition for human infections with avian influenza A(H5) virus requiring notification under IHR (2005): https://www.who.int/teams/global-influenzaprogramme/avian-influenza/case-definitions. 

    ° Virus sharing and risk assessment 

        • It is critical that these influenza viruses from animals or from humans are fully characterized in appropriate animal or human health influenza reference laboratories. Under WHO’s Pandemic Influenza Preparedness (PIP) Framework, Member States are expected to share influenza viruses with pandemic potential on a timely basis {12} with a WHO Collaborating Centre for influenza of GISRS. The viruses are used by the public health laboratories to assess the risk of pandemic influenza and to develop candidate vaccine viruses.  

        • The Tool for Influenza Pandemic Risk Assessment (TIPRA) provides an in-depth assessment of risk associated with some zoonotic influenza viruses – notably the likelihood of the virus gaining human-to-human transmissibility, and the impact should the virus gain such transmissibility. TIPRA maps relative risk amongst viruses assessed using multiple risk elements. The results of TIPRA complement those of the risk assessment provided here, and those of prior TIPRA risk assessments are published at http://www.who.int/teams/global-influenza-programme/avianinfluenza/tool-for-influenza-pandemic-risk-assessment-(tipra).  

    ° Risk reduction 

        • Given the observed extent and frequency of avian influenza in poultry, wild birds and some wild and domestic mammals, the public should avoid contact with animals that are sick or dead from unknown causes, including wild animals, and should report dead birds and mammals or request their removal by contacting local wildlife or veterinary authorities.  

        • Eggs, poultry meat and other poultry food products should be properly cooked and properly handled during food preparation. Due to the potential health risks to consumers, raw milk should be avoided. WHO advises consuming pasteurized milk. If pasteurized milk isn’t available, heating raw milk until it boils makes it safer for consumption. 

        • WHO has published practical interim guidance to reduce the risk of infection in people exposed to avian influenza viruses. 

    ° Trade and travellers 

        • WHO advises that travellers to countries with known outbreaks of animal influenza should avoid farms, contact with animals in live animal markets, entering areas where animals may be slaughtered, or contact with any surfaces that appear to be contaminated with animal excreta. Travelers should also wash their hands often with soap and water. All individuals should follow good food safety and hygiene practices.  

        • WHO does not advise special traveller screening at points of entry or restrictions with regards to the current situation of influenza viruses at the human-animal interface. For recommendations on safe trade in animals and related products from countries affected by these influenza viruses, refer to WOAH guidance.  

Links:  

° WHO Human-Animal Interface web page https://www.who.int/teams/global-influenza-programme/avian-influenza 

° WHO Influenza (Avian and other zoonotic) fact sheet https://www.who.int/news-room/fact-sheets/detail/influenza-(avian-and-other-zoonotic) 

° WHO Protocol to investigate non-seasonal influenza and other emerging acute respiratory diseases https://www.who.int/publications/i/item/WHO-WHE-IHM-GIP-2018.2 

° WHO Public health resource pack for countries experiencing outbreaks of influenza in animals:  https://www.who.int/publications/i/item/9789240076884 

° Cumulative Number of Confirmed Human Cases of Avian Influenza A(H5N1) Reported to WHO  https://www.who.int/teams/global-influenza-programme/avian-influenza/avian-a-h5n1-virus 

° Avian Influenza A(H7N9) Information https://www.who.int/teams/global-influenza-programme/avian-influenza/avian-influenza-a-(h7n9)virus 

° World Organisation of Animal Health (WOAH) web page: Avian Influenza  https://www.woah.org/en/home/ 

° Food and Agriculture Organization of the United Nations (FAO) webpage: Avian Influenza https://www.fao.org/animal-health/avian-flu-qa/en/ 

° WOAH/FAO Network of Expertise on Animal Influenza (OFFLU) http://www.offlu.org/ 

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{1} This summary and assessment covers information confirmed during this period and may include information received outside of this period. 

{2} For epidemiological and virological features of human infections with animal influenza viruses not reported in this assessment, see the reports on human cases of influenza at the human-animal interface published in the Weekly Epidemiological Record here.  

{3} World Organisation for Animal Health (WOAH). Avian influenza. Global situation. Available at: https://www.woah.org/en/disease/avian-influenza/#ui-id-2. 

{4} Food and Agriculture Organization of the United Nations (FAO). Global Avian Influenza Viruses with Zoonotic Potential situation update. Available at: https://www.fao.org/animal-health/situation-updates/global-aiv-withzoonotic-potential. 

{5} World Health Organization (2012). Rapid risk assessment of acute public health events. World Health Organization. Available at: https://iris.who.int/handle/10665/70810. 

{6} World Health Organization. Case definitions for the four diseases requiring notification in all circumstances under the International Health Regulations (2005). Available at: https://www.who.int/publications/m/item/case-definitions-for-the-four-diseases-requiring-notification-towho-in-all-circumstances-under-the-ihr-(2005).  

{7} World Organisation for Animal Health. Statement on High Pathogenicity Avian Influenza in Cattle, 6 December 2024 (https://www.woah.org/en/high-pathogenicity-avian-influenza-hpai-in-cattle/). 

{8} World Health Organization. International Health Regulations (2005), as amended through resolutions WHA67.13 (2014), WHA75.12 (2022), and WHA77.17 (2024) (https://apps.who.int/gb/bd/pdf_files/IHR_20142022-2024-en.pdf). 

{9} World Health Organization. Case definitions for the four diseases requiring notification in all circumstances under the International Health Regulations (2005) (https://www.who.int/publications/m/item/casedefinitions-for-the-four-diseases-requiring-notification-to-who-in-all-circumstances-under-the-ihr-(2005)). 

{10} World Health Organization. Manual for the laboratory diagnosis and virological surveillance of influenza (2011) (https://apps.who.int/iris/handle/10665/44518). 

{11} World Health Organization. Pandemic influenza preparedness framework for the sharing of influenza viruses and access to vaccines and other benefits, 2nd edition (https://iris.who.int/handle/10665/341850). 

{12} World Health Organization. Operational guidance on sharing influenza viruses with human pandemic potential (IVPP) under the Pandemic Influenza Preparedness (PIP) Framework (2017) (https://apps.who.int/iris/handle/10665/259402). 

Source: 

Link: https://www.who.int/publications/m/item/influenza-at-the-human-animal-interface-summary-and-assessment--7-july-2026

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Immunoinformatics-Guided Design and In Silico Evaluation of a Multi-Epitope #Vaccine Against #Influenza A #H10N5 and #H3N2 Strains Based on HA and NA Proteins

 

Abstract

Influenza A viruses H3N2 and H10N5 represent, respectively, a persistently dominant seasonal pathogen and a newly documented zoonotic threat with the latter strain variants responsible for the first confirmed human fatality in January 2024, yet no vaccine platform currently addresses co-protection against both subtypes within a unified immunogen. We report here the immunoinformatics based vaccine design and multi-layered computational validation of a 419-amino-acid multi-epitope subunit vaccine construct targeting conserved hemagglutinin (HA) and neuraminidase (NA) antigens identified through multiple sequence alignment of the avian H10N5 (A/swine/Hubei/10/2008) and H3N2 human reference strain sequences to identify viral agents undergoing mammalian adaptations. Linear B-cell, cytotoxic T lymphocyte (CTL), and helper T lymphocyte (HTL) epitopes were predicted using ABCpred, BCEpred, BepiPred 2.0, NetMHCpan 2.1, and NetMHCpan 4.0, then filtered through VaxiJen 3.0, AllerTOP v2.1, and ToxinPred to retain only antigenic, non-allergenic, non-toxic candidates. The final construct, incorporating an avian β-defensin N-terminal adjuvant with GPGPG, AAY, and EAAAK linkers, exhibited a molecular weight of 43.9 kDa, instability index of 31.15, and SOLPro solubility probability of 0.763. Tertiary structure modeling via I-TASSER and GalaxyRefine achieved 84.4% Ramachandran-favored residues. Molecular docking against TLR3 and TLR7 yielded binding free energies of −16.1 and −16.8 kcal/mol with picomolar dissociation constants. Molecular dynamics simulations confirmed complex stability over extended trajectories. Furthermore, codon optimization produced a Codon Adaptation Index of 1.0 for E. coli K12 expression. In silico immune simulation demonstrated robust activation of humoral and cellular immunity including elevated IgG1, IgM, IFN-γ, IL-2, rapid NK cell expansion, and broad B-cell clonal diversity. These findings establish a computationally validated candidate capable of providing protection against influenza in multiple host organisms, warranting experimental advancement.

Competing Interest Statement

The authors have declared no competing interest.

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.07.03.736294v1

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#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

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#Vaccine #strategies and #development before and during the 1968 #H3N2 #influenza #pandemic

 

Abstract

Nearly 60 years ago, in 1968, the global population was confronted with the emerging pandemic influenza A virus (IAV) subtype H3N2 (1968 H3N2pdm). An estimate of up to two million fatalities have been linked to 1968 H3N2pdm, and the H3N2 subtype continues to circulate as seasonal IAV among humans until today. The last IAV pandemic dates back to the year 2009 but concerns about a new IAV pandemic in the near future are increasing. The global spread of H5N1 highly pathogenic avian influenza virus and its spill-over into new mammalian hosts, discovery of novel influenza A virus with zoonotic or even pandemic potential, as well as seasonal influenza viruses undergoing antigenic changes necessitate constant vigilance. Here, we highlight the proactive actions, precautionary measures and vaccination strategies used during the 1968 H3N2 IAV pandemic. Our review highlights the emergence and spread of 1968 H3N2pdm over the course of the pandemic, alongside a delineation of vaccine development before, during and after the 1968 pandemic. Updating these strategies in the context of new findings combined with our experiences during the coronavirus disease 2019 (COVID-19) pandemic is necessary to improve preparedness for the next pandemic. Influenza viruses with zoonotic potential will remain a constant threat to public health, and improving countermeasures and communication to the public is key to limit the pandemic ramifications.

Source: 

Link: https://www.sciencedirect.com/science/article/abs/pii/S0264410X26006869?via%3Dihub

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#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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Identification of HLA-A33-restricted #CD8+ T cell epitopes from avian #influenza #H5N1

 

Abstract

The rapid evolution of avian influenza A/H5N1, including the recent U.S. clade 2.3.4.4b outbreak, highlights its pandemic potential and the urgent need for durable, broadly protective vaccines. Given the capacity of CD8+ T cells to mediate cross-strain immunity, we investigated whether geographically distinct HLA-A33 allotypes, HLA-A*33:01 in East/Southeast Asia and HLA-A*33:03 in South Asia, differentially shape the influenza immunopeptidome and influence antiviral immunity. Antigen-presenting cells overexpressing HLA-A*33:01 or HLA-A*33:03 were transfected with single A/H5N1 antigens or infected with A/X-31 (H3N2) as a control comparison representing current seasonal influenza virus. We identified novel ligands restricted to HLA-A*33:01 (57 from A/H5N1; 55 from A/X-31) and HLA-A*33:03 (29 from A/H5N1; 45 from A/X-31). Although fewer peptides were recovered for HLA-A*33:03, a larger proportion of A/X-31-derived peptides were predicted as high-affinity binders (74%) compared with HLA-A*33:01 (61%), indicating qualitative differences in antigen presentation. To determine immunogenicity, peripheral blood lymphocytes from HLA-A*33:03-positive, A/H5N1-naïve donors were stimulated with four conserved peptides: PB2GTF, PB2KTY, NPSVQ and PB1MTK. All elicited robust CD8+ T cell activation despite the absence of prior A/H5N1 exposure, demonstrating cross-recognition by memory T cells primed against seasonal influenza. These findings define HLA-A33-restricted influenza epitopes and reveal allotype-specific presentation features that shape CD8+ T cell immunity. Conserved, immunogenic peptides identified here represent promising candidates for rational design of broadly cross-reactive vaccines to protect HLA-A33-expressing populations against severe A/H5N1 disease. Data are available via ProteomeXchange with identifier PXD078870.

Competing Interest Statement

AWP is a scientific advisor for Bioinformatics Solutions Inc (Canada), a shareholder and scientific advisor for Evaxion Biotech (Denmark), and a co-founder of Resseptor Therapeutics (Australia). These organisations had no role in the design of the study in the collection, analyses, or interpretation of data in the writing of the manuscript or in the decision to publish the results. All other authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Funder Information Declared

NHMRC, 1122099, 2016596

Source: BioRxIV, https://www.biorxiv.org/

Link: https://www.biorxiv.org/content/10.64898/2026.06.21.733083v1

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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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Seasonal #vaccine-induced #immunity shows preserved cross-reactivity to #H3N2 subclade K in adults

 

Summary

Background

Influenza A subclade K viruses caused high infection rates in the 2025/2026 Northern Hemisphere season, raising concerns about antigenic drift and reduced vaccine effectiveness.

Methods

We measured antibody responses in matched human pre- and post-vaccination sera, selected from two observational cohort studies of adults, against both a vaccine-like as well as subclade K isolates.

Findings

Pre-existing immunity to subclade K variants was noted with seasonal influenza vaccination further boosting titres two-fold against subclade K and three-fold against the vaccine-like strain, consistent with limited antigenic divergence between subclade K isolates and the vaccine. These findings contrast with ferret-based predictions of marked antigenic drift and align with the observed vaccine effectiveness in adults.

Interpretation

Our results underscore the importance of incorporating human serologic data in influenza surveillance to better inform vaccine strain selection and anticipate vaccine performance in immunologically experienced populations.

Funding

NIAID Centers for Excellence in Influenza Research and Response (75N93021C00014); NIAID VIVA HIPC (U19 AI168631); Mount Sinai Center for Vaccine Research and Pandemic Preparedness; institutional support from the Mount Sinai Center for Vaccine Research and Pandemic Preparedness and the Medical University of Vienna.

Source: 

Link: https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(26)00203-3/fulltext

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The #canine respiratory #epithelium is a permissive #ecosystem for #influenza interspecies #transmission and emergence

 

Abstract

The outcome of virus spillover ranges from dead-end infections to pandemics and is underpinned by host-pathogen interactions as well as evolutionary and epidemiological processes. The emergence of novel influenza A viruses (IAVs) has been associated with reassortment events involving multiple species, highlighting the importance of reservoir and intermediate hosts in viral emergence. Highly pathogenic H5N1 IAVs of the 2.3.4.4b genotype have caused a panzootic affecting a broad range of mammals. The role of dogs -arguably the most popular companion animal and a natural host of IAVs- in the ecology of IAVs under this new zooepidemiological scenario is unknown. To address this, we characterised the glycome of the dog respiratory epithelium, infected canine tracheal explants with multiple IAVs (including canine H3N2 and H3N8, equine H3N8, avian H3N8 and H5N1, swine H1N1, human H1N1 and H3N2, and bovine H5N1 viruses), and determined their cellular tropism. We show that the respiratory tract of dogs presents abundant sialylated glycans known to act as IAV receptors. Further, most IAVs (including 2.3.4.4b viruses) infected and replicated in dog tracheas, targeting mainly ciliated cells. Serological testing showed evidence of influenza spillover infections in dogs from the UK. Overall, our results show that the canine respiratory tract can provide a suitable environment for the generation of new IAVs. Given the multi-host contact networks of dogs in nature, they could act as recipients, bridging hosts, and/or mixing vessels for multiple IAV lineages, playing a central role in the ecology of influenza emergence.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

Medical Research Council, https://ror.org/03x94j517, MR/Y03368X/1, MC_UU_0034/2, MC_UU_0034/3

Biotechnology and Biological Sciences Research Council, BB/Y007093/1, BB/Y007298/1, BBS/E/PI/230001A, BBS/E/PI/230002A, BBS/E/PI/230002B, BBS/E/PI/230001C

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.06.04.730051v1

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Broad heterologous #protection against #Influenza A viruses by an adjuvant-free modular mucosal T-cell #vaccine #platform

 

Abstract

Rapid antigenic evolution of Influenza A viruses (IAVs) enables their escape from strain-specific vaccine immunity, underscoring the need for broadly protective strategies. Here, we describe a modular, adjuvant-free mucosal vaccine platform that elicits potent and cross-protective T cell immunity. The approach uses overlapping CD4+ and CD8+ epitope-dense regions from the consensus IAV M1 and NP proteins, identified through computational and functional screening. These peptides are delivered using polylactic-co-glycolic acid (PLGA) microparticles, engineered for selective uptake by antigen-presenting cells and enabling sustained, pH-responsive antigen release. This design enhances antigen processing and MHC cross-presentation, functionally substituting for a conventional adjuvant. This formulation drives robust activation of primed human as well as murine CD4+ and CD8+ T cells and confers broad protection against homologous (H1N1, H3N2) as well as heterologous (H5N1) IAV strains in immunized mice. Overall, this adjuvant-free dose-sparing platform establishes an adaptable framework for next-generation broadly-protective vaccines against rapidly evolving viruses.

Competing Interest Statement

R.T.Y. and S.T. are co-inventors on an unpublished patent titled Immunogenic peptide(s), composition(s) and application(s) thereof broadly protective against Influenza, Indian patent application number 202541082426. The other authors declare that they have no competing interests.

Funder Information Declared

DBT-ENDFLU, BT/IN/EU-INF/15/RV/19-20

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.03.29.715080v2

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Breeding #pig #transport drives the dispersal of #swine #influenza A virus across #Europe

 

Abstract

Pigs serve as reservoirs of former human influenza A virus (IAV) H1N1 and H3N2 lineages and act as mixing vessels for diverse strains, facilitating the emergence of novel IAVs. Understanding the spread and evolution of swine IAVs (swIAVs) is therefore crucial to assess the risk of strains with zoonotic potential emerging. This study uses a phylogeographic framework to investigate the predictors of swIAV dispersal across Europe. All publicly available swIAV genomic sequences were retrieved and subsampled for the ten largest European pig-producing countries. Discrete phylogeographic reconstructions were conducted for H1, H3, N1, N2 encoding genes and all internal gene segments. Our analyses indicate that viral dispersal predominantly occurred from north-western to southern and eastern Europe, with frequent long-distance transitions between non-adjacent countries. We also extended the discrete phylogeographical analyses with generalized linear models to test the association between viral movement and potential predictors, such as live pig trade, pork trade, pig densities, farm sizes, or the geographic distance between key pig production zones. We find that breeding pig trade is the only consistently well-supported predictor of between-country transition events, whereas pork trade and geographic distance were not supported. This highlights that farms importing breeding pigs from multiple countries could act as hotspots for reassortment of diverse swIAV strains. Strengthening external biosecurity on farms with emphasis on quarantining breeding pigs, limiting long-distance transport, and implementing a One Health surveillance system for earlier detection of emerging strains, could help curb the rapid spread and evolution of swIAV in Europe.

Competing Interest Statement

The authors have declared no competing interest.

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.06.01.729471v1

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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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Understanding the emergence of the #influenza #H3N2 K #subclade in its historical and evolutionary context

Abstract

The emergence in 2025/26 of the influenza A/H3N2 K substrain (H3N2/K) was the cause of significant public health concern. This genetically divergent virus was assessed to have a strongly decreased reactivity to contemporary vaccine strains. Respectively prolonged and early influenza seasons in the Southern and Northern Hemispheres contributed to concerns about vaccine efficacy. Here we retrospectively assessed the genetic and antigenic properties of this virus, combining epidemiological surveillance data, computational antigenic analysis, and serological data using samples from a well-stratified UK cohort. In contrast to initial indications, we found that despite the genetic distinctiveness of H3N2/K the virus had undergone limited antigenic change, suggesting that its emergence was instead the result of selection for non-antigenic properties. We confirmed previous results showing that contemporary vaccines produced an enhanced neutralising response to H3N2/K but, in a stratified serological analysis, showed that responses to the J and K substrains were age-dependent, largely driven by patterns of vaccination. Our results have implications for antigenic surveillance and for public communication strategies in future influenza seasons.

Competing Interest Statement

PRM declares funding by MSD. EH has received an honorarium for advisory board work for Seqirus.

Funder Information Declared

Medical Research Council, MR/Y03368X/1, MC_UU_0034/1, MC_UU_0034/2, MC_UU_0034/3, MC_UU_0034/5, MC_UU_0034/6

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.05.21.726823v1

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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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Prior #immunity to seasonal #influenza #H3N2 virus confers varying levels of cross - #protection against challenge with clade 2.3.4.4b #H5N1, #H7N9, or #H9N2 virus in a #ferret model

 

ABSTRACT

Evaluating how prior immunity to seasonal influenza viruses influences subsequent zoonotic influenza A virus (IAV) infection in animal models is critical for pandemic preparedness. In this study, we investigated the cross-protective effect of pre-existing A(H3N2) immunity in ferrets challenged with three distinct subtypes of zoonotic IAVs: low pathogenic A(H7N9) and A(H9N2) viruses, and highly pathogenic clade 2.3.4.4b A(H5N1) virus. Our results show that A(H3N2) preimmunity conferred some protection against A(H5N1) and A(H9N2) virus infection, as evidenced by more rapid viral clearance in the upper respiratory tract, reduced virus shedding in the nasal wash on select days post-inoculation, and a lowered frequency of viral detection in specific tissues compared with naive animals. In contrast, A(H3N2) preimmunity provided minimal cross-protection against A(H7N9) infection, as weight loss and viral dissemination in tissues were not significantly reduced in A(H3N2) preimmune ferrets relative to naive animals. These findings highlight the variable breadth and magnitude of cross-protection elicited by prior seasonal IAV immunity against zoonotic influenza virus challenges in the ferret model. Seasonal influenza A(H3N2) preimmunity provided differing levels of cross-protection against zoonotic influenza A virus infections in ferrets.

Source: 

Link: https://journals.asm.org/doi/10.1128/spectrum.03974-25

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