#Chile - #Influenza A #H5N1 viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Immediate notification

 

Backyard captive birds in Los Lagos Region.

Source: 

Link: https://wahis.woah.org/#/in-review/7802

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#France - High pathogenicity avian #influenza #H5N1 viruses (Inf. with) (#poultry) - Immediate notification

 

A farm with vaccinated ducks in Maine-et-Loire Region.

Source: 

Link: https://wahis.woah.org/#/in-review/7800

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Immunogen selection and prior #immunity shape #antibody breadth following immunisation with avian #H5 #hemagglutinin

 

Abstract

Avian influenza A viruses pose a persistent zoonotic threat to humans owing to their expanding host range and high case fatality rates. In particular, viruses from the 2.3.4.4b clade of the H5 subtype have now been detected in over 60 mammalian species, raising serious pandemic concerns. Understanding immune recognition of the H5 hemagglutinin (HA) is therefore critical for effective vaccine design and pandemic preparedness. To understand the breadth of cross-recognition induced by different H5 strains, we selected genetically diverse H5 human isolates from 2003-2023 and assessed neutralising antibody responses elicited by adjuvanted recombinant HA protein-based vaccines in C57BL/6 mice. Neutralisation activity of sera was determined against seven H5 HA variants using pseudotyped viruses and a PR8-reassortant virus in micro-neutralisation assays. Our results showed a wide variety of cross-strain neutralisation across H5 HA antigen variants. The conventional vaccine strain A/Indonesia/05/2005 displayed narrow activity against emerging clade 2.3.4.4b viruses, whereas ancestral variants exhibited cross-neutralisation profiles showing a diversity of breath but with limited potency. Polyvalent H5 HA formulations and nanoparticle-displayed H5 HA platforms substantially broadened cross-neutralisation against diverse H5 strains. To examine the impact of pre-existing immunity on H5 vaccine immunogenicity in mouse models, mice were primed with either seasonal influenza infection or quadrivalent influenza vaccine (QIV) prior to H5 HA immunisation. QIV pre-vaccination, but not prior influenza infection, enhanced subsequent neutralizing responses towards A/Fujian-Sanyuan/21099/2017 (clade 2.3.4.4b) H5. Collectively, our results demonstrate that immunogen selection and prior immunity shape antibody breadth following immunisation with avian A(H5) hemagglutinin.

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.09.01.748495v1

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#Genome-informed structural #analysis of #polymerase and glycoprotein #adaptation in #H5N1 clade 2.3.4.4b

 

Abstract

Importance

Understanding the molecular mechanisms driving H5N1 clade 2.3.4.4b is critical for pandemic preparedness.

Objective

To characterize the molecular drivers of viral fitness and mammalian adaptability in recent H5N1 viruses by integrating evolutionary dynamics with structural simulations.

Methods

This study analyzed 2,398 H5Nx genomes (2000–2024) through phylogenetic and selective pressure analyses. HA/NA structures were predicted with AlphaFold 3 and evaluated by AutoDock4 docking, whereas polymerase–ANP32A/B complexes were modeled using template-based methods and their binding free energies were estimated using MM/GBSA. Polymerase–ANP32E complexes were predicted with AlphaFold 3 and similarly evaluated by MM/GBSA. The binding affinities (ΔG) for the sialic acid (SA) receptors and human ANP32 proteins were quantified through molecular mechanics/generalized born surface area calculations.

Results

Clade 2.3.4.4b showed significant antigenic drift in the HA receptor binding site, reducing affinity for α2,3-SA and α2,6-SA receptors. On the other hand, the emergence of a full-length stalk N1 NA with second sialic acid-binding site mutations (e.g., N366S) compensated for reduced HA affinity by enhancing the NA binding stability. In the polymerase complex, both the PB2-627E/631L variant (−144.00 kcal/mol; unadjusted p = 0.0058) and the known mammalian-adaptive 627K/631M variant (−144.67 kcal/mol; unadjusted p = 0.0165) showed more favorable predicted human ANP32B binding free energies than the ancestral 627E/631M state (−136.46 kcal/mol).

Conclusions and Relevance

The co-occurrence of HA, NA, PB1, and PB2 signatures was associated with clade expansion and produced structural predictions consistent with altered receptor or ANP32 interactions; experimental validation is required before inferring effects on fitness or zoonotic risk.

Source: 

Link: https://vetsci.org/DOIx.php?id=10.4142/jvs.26088

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The first high pathogenicity avian #influenza #H5N1 clade 2.3.4.4b incursions in Hunter New England region, NSW, #Australia, June–July 2026

 

Abstract

Two incursions of high pathogenicity avian influenza (HPAI) A(H5N1) clade 2.3.4.4b in vagrant birds were identified in the Hunter New England region of New South Wales, Australia on 28 June 2026 and 10 July 2026. These were the first detections of the virus in New South Wales and occurred shortly after the first Australian detection in June 2026. The Hunter New England Population Health Unit managed human contacts of the infected birds using a contact management system designed and purpose-built by the Unit. We report on the public health response and opportunities for improvement.

Source: 

Link: https://ojs.cdi.cdc.gov.au/index.php/cdi/article/view/3492

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#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

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Chinese #Taipei - High pathogenicity avian #influenza #H5N1 viruses (Inf. with) (#poultry) - Immediate notification

 

    ° A recurrence of high pathogenicity avian influenza (HPAI) subtype H5N1 (clade 2.3.4.4b) was detected in native chickens at a slaughterhouse in Taipei City, Chinese Taipei. 

    ° On August 8, clinical signs were identified during postmortem inspection by the resident veterinarian, who immediately notified the Local Animal Disease Inspection Authority of Taipei City. 

    ° On the same day, diagnostic samples were collected and sent to the National Reference Laboratory; concurrently, the other 25 native chickens from the same source were depopulated and placed in frozen storage. 

    ° Following official confirmation of the positive case on August 10, the frozen carcasses were destroyed on August 11, with cleaning and disinfection completed thoroughly. 

    ° Trace-back investigation was immediately initiated, and the source poultry farm was placed under movement restriction; subsequent diagnostic testing yielded negative results for avian influenza nucleic acid. 

    ° There are no poultry farms within 3 kilometers of the slaughterhouse.

Source: 

Link: https://wahis.woah.org/#/in-review/7778

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Pre-existing systemic and #nasal #antibodies against avian #H5 #influenza A viruses vary according to childhood #imprinting

 

ABSTRACT

Avian influenza A viruses (IAVs) pose a constant pandemic threat, with the recent 2.3.4.4b clade of the H5 subtype causing high pathogenicity and spreading across animal species and geographic locations. Understanding human pre-existing immunity to avian H5 IAV can inform on population susceptibility, a critical aspect of pandemic preparedness. To that end, we analyzed the IAV HA-specific antibodies across individuals born between 1928 and 1999 with different early life exposures to IAV subtypes. Individuals born prior to 1957 had the highest pre-existing serum antibodies to group 1 HA antigens, including the 2.3.4.4b H5 and a group 1 HA stem antigen. These birth year-specific patterns were not reflected in the limited pre-existing serum neutralizing antibodies detectable against a 2.3.4.4b H5 IAV or in H5-specific memory B cell populations. They were, however, evident in pre-existing nasal IgG and IgA titers to H5, which were greater in individuals born prior to 1957. Our findings demonstrate that the immunological biases afforded by early life exposure extend to antibodies detected in the nasal mucosa, the site of IAV replication.

Source: 

Link: https://journals.asm.org/doi/10.1128/mbio.01892-26

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Impaired #Neuraminidase and Polymerase Activities Correspond With Limited Aerosol Infectivity of #B3.13 and #D1.1 #H5N1 Lineages in #Human Respiratory Cultures

 

Abstract

The ongoing panzootic of clade 2.3.4.4b highly pathogenic avian influenza (HPAI) H5N1 viruses has reached a critical point, marked by unprecedented mammalian spillover and sustained outbreaks in U.S. dairy cattle. While these viruses remain highly lethal in traditional ferret models, human infections-primarily linked to the B3.13 and D1.1 lineages-have been notably mild, typically presenting as conjunctivitis with minimal respiratory involvement. In this study, we address this disconnect by evaluating the infectivity of recent H5N1 isolates using a physiologically relevant air-liquid interface (ALI) culture system that incorporates an aerosol settling chamber. We demonstrate that while direct liquid inoculation leads to efficient replication, aerosolized H5N1 strains exhibit a significant defect in their ability to infect human respiratory epithelium. In contrast, a prototypic H5N1 virus remains highly pathogenic and lethal in ferrets regardless of the inoculation route, showing systemic dissemination to the brain and other organs. Our findings identify two primary viral determinants driving this respiratory restriction: reduced neuraminidase (NA) enzymatic activity and impaired polymerase activity. Collectively, these results suggest that commonly used mammalian models may overstate current human pandemic risk. This work highlights the critical need for alternative risk-assessment platforms to identify the specific genetic shifts required for these viruses to overcome existing barriers to human adaptation.

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.08.18.745466v1

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Emerging Haemagglutinin #Mutations in #Bovine-origin #H5N1 Influenza Viruses from #Humans and #Cattle Retain Avian #Receptor Binding with Increased Stability

 

Abstract

The current H5N1 panzootic has seen an unprecedented host range expansion, including sustained circulation in US dairy cattle, detected in March 2024. By July 2026, infections had been reported on more than 1,150 dairy farms across 19 states. Although the outbreak initially centred in Texas, California has emerged as the principal focus of transmission and accounts for most human infections associated with exposure to infected dairy cattle. Continued transmission in cattle and repeated spillover into humans increase opportunities for acquisition of mammalian-adaptive mutations that could elevate zoonotic and pandemic risk. The haemagglutinin (HA) protein plays a central role in modulating virus receptor binding and airborne transmission. Here, we characterised the receptor-binding and stability phenotypes of HA mutations identified in viruses circulating in Californian dairy cattle. Receptor-binding specificity was assessed using bio-layer interferometry and pseudotype virus entry assays. All tested HA variants maintained a preference for avian-type α2,3-linked sialic acid receptors. We evaluated HA stability using fusion and thermostability assays. All mutants exhibited fusion pH values >5.5, outside the range associated with efficient airborne transmission in humans (pH 5.0-5.5). However, mutations D88G and S94N increased pH stability, with fusion pH values of 5.6 and 5.7, respectively, compared with 5.9 for wild-type HA. Viruses harbouring both mutations displayed increased thermostability. These findings demonstrate that cattle-origin H5N1 viruses retain avian-like receptor specificity despite acquiring mutations that modestly enhance HA stability. Evolution of H5N1 viruses in dairy cattle underscores the importance of genomic and phenotypic surveillance to identify mutations that may increase zoonotic risk.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

Biotechnology and Biological Sciences Research Council, BB/X006166/1, BB/Y007298/1, BB/X006204/1 BB/Y007271/1, APP104179,, BBS/E/PI/230001B, BBS/E/PI/230001C, BBS/E/PI/230002B, BBS/E/PI/230002C), BBS/E/PI/23NB0004, BBS/E/PI/23NB0003, BB/S011269/1

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

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.08.18.745528v1

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Trimester-dependent vertical #transmission of #H5N1 #influenza virus through #placental and mammary routes impairs offspring development

 

Abstract

Avian influenza H5N1 has pandemic potential and historically causes more severe disease in pregnant women than the general population. With increasing transmission of H5N1 detected among placental mammals, animal models are necessary for testing countermeasures, including during pregnancy. Pregnant outbred mice infected with a contemporary strain of bovine H5N1 during the second trimester equivalent causes in utero transmission, with infectious virus detected in the uterus, placenta, and fetus. Birth following third trimester infection results in offspring with decreased size, neurodevelopmental delays, and adolescent behavioral impairments, with infectious virus detected in the neonatal milk ring and lungs, as well as mammary tissues. H5N1 viral protein colocalizes with trophoblast cells in the placenta and epithelial cells in mammary tissue that spatially overlap with lectins for α2,3-linked SA. With the pandemic potential of H5N1, our vertical transmission model in placental mammals is essential for understanding viral spread and evaluating treatments during pregnancy.

Source: 

Link: https://www.nature.com/articles/s41467-026-76891-9

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#Influenza at #human - #animal #interface - Summary & #risk #assessment, from 8 July to 7 August '26 (WHO, edited): 2 new #H5N1 cases in #Bangladesh & #Cambodia, 8 new #H9N2 cases in #China

Influenza at the human - animal #interface - Summary and risk assessment, from 8 July to 7 August 2026 {1}

    • New human cases {2}: 

        * From 8 July to 7 August 2026, based on reporting date, detections of influenza A(H5N1) in one human and influenza A(H9N2) in eight humans  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(H5N1), Bangladesh

        § The case included in the risk assessment of 7 July 2026 in a child from Sylhet Division was confirmed as an A(H5N1) virus infection.

    ° A(H5N1), Cambodia

        § On 10 July 2026, Cambodia notified WHO of one laboratory-confirmed human case of avian influenza A(H5N1) infection detected in a child in Phnom Penh who developed a fever on 30 June 2026. After several days of  treatment at a private clinic without improvement, she was admitted to hospital  on 7 July with bronchopneumonia. Oropharyngeal and nasopharyngeal swabs  collected on 8 July were tested at the Institut Pasteur du Cambodge and reverse  transcription polymerase chain reaction (RT-PCR) testing confirmed influenza  A(H5N1) on 10 July, with positive results confirmed through repeat testing. The  specimen was subsequently tested at the National Institute of Public Health, which  also confirmed influenza A(H5N1). The patient was in stable clinical condition, treated with oseltamivir and subsequently recovered.

        § Sequence analysis identified the virus as a clade 2.3.2.1e virus,  closely related to viruses that have been circulating in poultry and causing  sporadic human infections in Cambodia since 2023.

        § Following laboratory confirmation, the national and Phnom Penh  Municipal Rapid Response Teams, in collaboration with the Ministry of Agriculture,  Forestry and Fisheries and local authorities, initiated epidemiological,  environmental and animal health investigations, including active case finding and assessments of potential poultry and environmental exposures. 

        § Neighbouring households kept fighting cocks and free-range chickens  and the patient visited one of these households prior to symptom onset.  The child also had exposure to areas where chicken droppings were found. 

        § At the time of reporting, three animal samples collected from poultry  in neighbouring households for laboratory testing tested negative for influenza  A(H5N1). 

        § Contacts of the case tested negative for influenza A(H5N1) and two  tested positive for SARS-CoV-2.

        § Since 2023, Cambodia has reported 39 laboratory-confirmed human cases, including 16 deaths.

Risk assessment for avian influenza A(H5N1) viruses:

    1. What is the current global public health risk of additional human cases of  infection with avian influenza A(H5N1) viruses?

        ° Most human infections so far have been reported in people exposed to  A(H5N1) 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(H5N1) 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(H5N1) 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(H5N1) 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(H5N1) 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 7 July and 5 August 2026, China notified WHO of eight laboratory-confirmed human cases of A(H9N2) virus infection. 

{Click on Image to Enlarge}

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        § All cases had direct or indirect exposure to poultry and/or 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.

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_2014-2022-2024-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-august-2026

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A novel candidate #vaccine virus derived from #Japan's first #mammalian case of clade 2.3.4.4b #H5N1 highly pathogenic avian #influenza virus

 

Abstract

The development of candidate vaccine viruses (CVVs) for pre-pandemic preparedness requires attenuation of pathogenicity while maintaining immunogenicity. In this study, we developed and characterized NIID-002, a reassortant virus derived from A/Ezo red fox/Hokkaido/1/2022 (H5N1; clade 2.3.4.4b), to evaluate its suitability as a candidate vaccine. NIID-002 exhibited markedly reduced pathogenicity compared with its parental strain, while retaining broad antigenic reactivity and protein yield comparable to other clade 2.3.4.4b CVVs. In mammalian models, NIID-002 demonstrated strong attenuation, causing no lethal infection in mice and only minimal weight loss with limited viral replication in ferrets. Antisera raised against NIID-002 reacted broadly with recent wild-type H5N1 isolates, suggesting potential broad protection. Protein yield analysis confirmed a production efficiency comparable to that of other CVVs within the same clade, supporting its feasibility for large-scale vaccine manufacturing. Overall, NIID-002 fulfills the key requirements for the pandemic preparedness of CVV, combining reduced pathogenicity, broad antigenic reactivity, and adequate production efficiency. These findings highlight its potential as a candidate H5N1 vaccine and underscore the continued need for surveillance and refinement of influenza vaccine strategies to address evolving viral threats.

Source: 

Link: https://www.sciencedirect.com/science/article/abs/pii/S0264410X26008571?via%3Dihub

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Enhanced #Pathogenicity and Contact #Transmissibility of #Human-origin Avian #Influenza #H5N1 Clade 2.3.4.4b Genotype B3.13 Compared to D1.1 in #Ferrets

 

Abstract

Since its emergence in 2020, multiple genotypes of the H5N1 clade 2.3.4.4b have been identified, with B3.13 and D1.1 emerging in the USA as two major and concerning genotypes. However, their relative pathogenicity and transmissibility in mammals have not been fully elucidated. We compared the pathogenicity and transmissibility of the first two human H5N1 clade 2.3.4.4b cases caused by B3.13 in Texas (A/Texas/37/2024; HPhTX B3.13) and D1.1 in Louisiana (A/Louisiana/12/2024; HPhLA D1.1) in a ferret model of infection and transmission. HPhTX B3.13 infection resulted in more severe clinical disease and enhanced viral shedding, with evidence of increased transmission relative to HPhLA D1.1. Histopathological analysis revealed more extensive lung pathology in animals infected with HPhTX B3.13, consistent with increased viral loads and inflammatory responses. Importantly, both genotypes showed no significant differences in reactivity to ferret sera raised against candidate vaccine virus (CVV) strains, receptor binding properties, or neuraminidase (NA) activity and thermostability. Whole-genome sequencing revealed no adaptive mutations in HPhTX B3.13 following infection or transmission. In contrast, HPhLA D1.1 showed rapid acquisition of the mammalian-adaptive mutation E627K in infected ferrets and both E627K and Q194K in the only fatal contact animal. Both mutations were associated with enhanced polymerase activity and computational analyses suggested that they enhance interactions with the mammalian host factors ANP32A and B. Our findings indicate that B3.13 is already well adapted for mammalian infection and transmission whereas D1.1 retains evolutionary potential through the rapid acquisition of adaptive mutations, highlighting important genotype-specific differences relevant to zoonotic risk assessment and pandemic preparedness.

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, Prosetta and A.A.C.T., 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 Icahn School of Medicine at Mount Sinai has licensed some of these inventions to Medimmune, Avimex, Leinco Technologies, Castlevax, Virofend, Kerafast, Cell Signaling, EMD Millipore, Genentech, Paratus and Nura Bio, and as a result receives financial compensation. Subject to Mount Sinai receiving such financial consideration, AG-S will receive a portion of that consideration pursuant to the terms of the Mount Sinai Intellectual Property Policy. All other authors declare no commercial or financial conflict of interest.

Funder Information Declared

NIH/NIAID, 75N93021C00014

Horizon Europe Program, KAPPA-FLU no. 101084171

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.08.10.744032v1

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#Chile - #Influenza A #H5N1 viruses of high pathogenicity (Inf. with) (non-poultry including wild birds) (2017-) - Immediate notification

 

The date of last occurrence corresponds to the end date of the most recent event involving backyard birds in Biobío region, involving birds that were not considered poultry as defined by the OIE Terrestrial Code.

Source: 

Link: https://wahis.woah.org/#/in-review/7757

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Identification and characterization of #PB2 #mutations associated with #mammalian #adaptation of highly pathogenic #H5N1 avian #influenza viruses

 

Abstract

The highly pathogenic avian influenza virus (HPAIV) subtype H5N1 has been continuously circulating among wild bird populations and domestic poultry. It’s ongoing circulation has led to outbreaks in poultry and U.S. dairy cattle populations, as well as sporadic severe infections in individuals engaged in poultry and dairy farming. These occurrences have raised concerns about the potential evolution of this virus into a pandemic strain. To elucidate the molecular determinants facilitating H5N1 cross-species adaptation and to evaluate its implications for public health, we conducted serials of sequence analysis and specific-site mutations on the viral polymerase subunit PB2 to determine its effect on polymerase activity and viral infectivity. The results showed that three mutations in the PB2 protein (E362G, D441N and M631L) were presented cooperative effects associated with enhanced viral replication in mammalian cells. Compared to the original isolated strain of the 2.3.4.4b clade, A/chicken/NL/FAV-0033/2021, these three mutations were predominantly identified in isolates obtained from cattle and other mammalian hosts between 2021 and 2024. The M631L mutation, identified as the primary determinant of increased polymerase activity in mammalian cells, significantly enhanced the binding affinity of PB2 to ANP32A. The mutation E362G and D441N did not increased polymerase activity and viral replication significantly but enhanced binding affinity of PB2 to ANP32A. The combined mutations with E362G, D441N and M631L resulted in a significantly increased polymerase activity and viral replication in H5N1 virus, and significantly elevated viral loads and aggravated pulmonary pathology in lungs of mice with H5N1 infection. These findings indicate that the PB2-M631L mutation constitutes a crucial molecular marker for the adaptation of H5N1 to mammalian hosts, whereas the E362G and D441N mutations likely function as supportive modulatory factors that optimize this host-adaptation process.

Source: 

Link: https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2026.1867604/full

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Protective Efficacy Evaluation of Various Inactivated #Vaccines Against the Newly Circulated Highly Pathogenic Avian #Influenza Virus #H5N1 of Clade 2.3.4.4b in Pekin #Ducks

 

Abstract

Highly pathogenic avian influenza (HPAI) virus H5N1of clade 2.3.4.4b has emerged as the predominant lineage circulating in poultry flocks worldwide, raising concerns regarding the protective efficacy of currently available commercial vaccines, particularly in domestic ducks, which play an important role in virus maintenance and transmission. Thus, this study evaluated the immunogenicity along with the protective efficacy of four inactivated H5 vaccines against a recently isolated local HPAI-H5N1 (Newvalley-3-H5N1-2024, clade 2.3.4.4b) strain in Pekin ducks in Egypt. A total of 150 seronegative ducks were divided into vaccinated and control groups (10 groups) and vaccinated at 10 days of age. At 31 days of age, the vaccinated and positive control groups were challenged using 106.5 EID50/0.5 mL/duck with the local isolate (Newvalley-3-H5N1-2024) via the oculo-nasal route. The vaccine efficacy was assessed through clinical signs, survival rate, hemagglutination inhibition (HI) antibody titer, tracheal and cloacal viral shedding quantified by real-time RT-PCR, and histopathological examination of trachea, lung, pancreas, and brain tissues. Generally, all ducks vaccinated with the ValleyVac Avian Flu H5 plus and MEFLUVACTM H5 PLUS 8 showed a significantly higher survival rate (100%) at 10 days post-vaccination (DPV) than those in the positive control (66.7% mortality rate). In contrast, ducks exhibited mortality rates ranging from 6.7% in the SERVAC Flu H5N1 group to 13.4% in the Sinder Fluvac group. The ValleyVac Avian Flu H5 plus and MEFLUVAC™ H5 PLUS 8 vaccines induced the highest HI antibody titers at 7, 14, 21, and 28 DPV in both homologous and heterologous AIV antigens, resulting in a significant reduction in viral load among all vaccinated duck groups (p-value < 0.05) comparable to the positive control group. Conversely, the SERVAC Flu H5N1 and Sinder Fluvac vaccines provided partial protection, suboptimal immunogenicity at different time points, and elevated viral shedding. Histopathological findings in ValleyVac Avian Flu H5 plus and MEFLUVAC™ H5 PLUS 8 vaccines exhibited mild tissue alterations following AIV challenge. Marked pathological lesions were observed in the SERVAC Flu H5N1 and Sinder Fluvac vaccinated groups. Among tested vaccines, both ValleyVac Avian Flu H5 plus and MEFLUVACTM H5 PLUS 8 showed the highest level of protective efficacy against the circulating AIV strain compared with other commercial vaccines. This study highlights the need for continuous molecular surveillance, antigenic matching, and regular updating of vaccine seed strains to ensure efficient HPAI control in Egypt.

Source: 

Link: https://www.mdpi.com/1999-4915/18/8/891

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