#Estimation of the #transmission #dynamics of #H5N1 HPAI #outbreak in a dairy #herd using a modeling approach

 

Abstract

The emergence of Highly Pathogenic Avian Influenza (HPAI 2.3.4.4b) in dairy herds in 2024 across 19 states in the United States of America has raised concerns regarding the potential national and global zoonotic impact. All recent modeling efforts implemented homogenous cattle-to-cattle (both intra and inter-herd) transmission models which did not capture the real-world heterogeneity in mixing of animals, individual variations in susceptibility and infectiousness and clinical incidences across pens and lactation groups. The aim of this study was to develop a heterogenous transmission model to estimate the epidemiological parameters for intra-herd HPAI transmission on Californian dairies. We developed a validated stochastic agent-based model to estimate the epidemiological parameters for intra-herd HPAI transmission on California dairies. The hierarchical agent-based model also parameterized stochastic cattle movements within-herd to simulate real dairy management practices. A cow-level SEIR transmission approach was assumed during the outbreak. A novel Bayesian Optimizer with Gaussian Process (BO-GP) was fitted to the agent-based model for validation which converged within 25-40 iterations (out of 100 per farm) with minimal loss over two distinct error metrics, namely, Poisson loss function and temporal distance metric. Our optimized simulations estimated an average R0 was around 10.7-10.8 across all farms within the first 15 days of observed outbreak on four dairy farms with a mean effective transmission rate of 4.5% per contact between susceptible and infectious cows within each pen. Our model demonstrated that the movement of cows between pens ensured localized clusters of outbreaks within the sub-herds (pen population) that prolonged the overall outbreak within farms. We estimated the total duration of infection between 14.5 and 28 days, which is higher than the estimates from the homogenous models. With an integrated hierarchical agent-based model combined with Bayesian approximation, we produced actionable insights on the epidemiology of intra-farm spread of HPAI within cow herds, thereby guiding both future model development and applied disease control strategy.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

Animal and Plant Health Inspection Service (USDA-APHIS), AP25VSD&B000C007

Source: 

Link: https://doi.org/10.64898/2026.09.22.753543

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Avian #influenza #overview June–August 2026 (ECDC/EFSA, September 22 '26, Summary)

 

{Summary}

Abstract

    Between 5 June and 28 August 2026, 110 highly pathogenic avian  influenza (HPAI) A(H5N1) virus detections were reported in domestic (7)  and wild (103) birds in 12 countries in Europe. The number of detections  remained at a seasonal low throughout the summer, continuing the decline  observed since spring. In contrast to previous years, fewer colony-breeding  seabirds were affected, and the geographical range of detections was more  limited. Further sporadic detections of HPAI A(H5) virus were reported in wild  terrestrial carnivores and pinnipeds. Outside Europe, the epidemic continued  in the Americas, where also the HPAI A(H7N3) subtype was detected in Mexico.  Following its first introduction to mainland Australia, HPAI A(H5N1) virus spread within local wild bird populations and spilled over to terrestrial  carnivores and marine mammals. In the US, the number of dairy  cattle farms reportedly affected by HPAI A(H5N1) increased, while detections in  captive American minks were reported for the first time. Between 5 June and  31 August 2026, 15 cases of avian influenza virus infection were publicly  reported in humans (no fatal cases) in three countries and territories:  Bangladesh (one A(H5N1) case), Cambodia (one A(H5N1) case) and China (13 A(H9N2) cases). All human cases reported exposure to poultry or a poultry  environment prior to detection or onset of illness. Human infections with avian  influenza viruses remain rare and no sustained human-to-human transmission has  been documented. The risk posed by avian influenza A(H5N1) clade  2.3.4.4b viruses currently circulating in Europe remains low for the general  public in the European Union/European Economic Area (EU/EEA) and low-to- moderate for those occupationally or otherwise exposed to infected animals or  contaminated environments.

©2026 European Food Safety Authority, European Centre for Disease Prevention  and Control, European Union Reference Laboratory for Avian Influenza. EFSA  Journal published by WileyVCH GmbH on behalf of European Food Safety Authority

(...)

Source: 

Link: https://doi.org/10.2903/j.efsa.2026

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Serological #Evidence of Widespread #Exposure to #H5 Avian #Influenza Virus in #Arctic #Foxes in #Svalbard, Norway

 

Abstract

The continued circulation of H5 clade 2.3.4.4b highly pathogenic avian influenza virus (HPAIV) has caused extensive mortality in wild bird populations worldwide with increasing spillover to mammals. In 2022, H5 HPAIV emerged in Svalbard, Norway, with subsequent detections in wild birds, walruses, polar bears, and arctic foxes. To understand the population-level exposure among Svalbard arctic foxes, we analysed body fluids from carcasses trapped in 2006-2015 (n = 56), 2023-2024 (n = 112), and 2024-2025 (n = 94) for antibodies to H5 avian influenza (anti-H5), influenza A nucleoprotein (anti-NP), and neuraminidase subtypes using ELISAs, haemagglutination inhibition (HI), and a multiplex assay. Only three samples from 2006-2015 tested positive for anti-H5 and were interpreted as false positives. In 2023-2024, seropositivity for anti-H5 was high (95%), supported by a lower anti-NP seropositivity (85%) and antibody profiles consistent with mixed H5N1 (42%) and H5N5 (52%) exposure. In 2024-2025, anti-H5 and anti-NP seroprevalences remained high (83% and 57%), with H5N5 (87%) exposure predominating over H5N1 (3%). A subset of anti-H5-positive samples tested positive by HI (2023-2024: 30%; 2024-2025: 14%). Juveniles with exposure limited to the previous season had higher odds of anti-H5 seropositivity in 2023-2024 than in 2024-2025 (OR 5.5). Analysis of paired lung extracts from a subset of individuals (n = 63) yielded results concordant with body fluids, using an indirect anti-H5 ELISA adapted for carnivores. Our findings demonstrate widespread H5 virus exposure. Together with occasional reports of progression to fatal HPAI, this highlights the need for continued population monitoring to evaluate ecological consequences.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

European Commission, https://ror.org/00k4n6c32, 101132473, 101084171

Dutch Research Council, ENWPP.SK.2025.001

Source: 

Link: https://doi.org/10.64898/2026.09.17.752278

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Limited added #benefit of seasonal #influenza #vaccination before #H5 vaccination in mice and #ferrets challenged with #H5N1

 

ABSTRACT

Limited A(H5)-specific vaccine supply is expected early in a potential A(H5N1) pandemic, raising the question of whether licensed seasonal influenza vaccines could enhance protection when administered before A(H5) vaccination. We evaluated this strategy in mouse and ferret models using clade 2.3.4.4b A(H5N1) viruses. Seasonal influenza vaccination induced antibodies to seasonal haemagglutinins but did not induce detectable antibodies against A(H5) and did not consistently enhance A(H5)-directed antibody responses after A(H5) vaccination. In lethal challenge studies, seasonal vaccine priming before A(H5) vaccination was associated with improved outcomes compared with A(H5) vaccination alone in one of three mouse experiments, but this effect was not observed in the other two mouse experiments or in ferrets. These findings suggest that seasonal influenza vaccine priming provides limited added benefit to A(H5) vaccine-mediated protection against A(H5N1) under the conditions tested.

Source: 

Link: https://doi.org/10.1080/22221751.2026.2731495

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First detection of High pathogenicity Avian #Influenza #H5N1 Clade 2.3.4.4b Genotype EA-2024-DI.2.1 in #Egypt associated with migratory wild birds

 

Abstract

High pathogenicity avian influenza (HPAI) H5 clade 2.3.4.4b is the main driver of the ongoing unprecedented global panzootic. The recently emerged HPAI H5N1 clade 2.3.4.4b genotype EA-2024-DI.2.1 has become predominant in Europe, with migratory wild birds, particularly waterfowl, playing a major role in its dissemination. Egypt lies along major Afro-Eurasian migratory flyways, which have historically played an important role in the introduction of emerging H5Nx viruses into the country. In this study, targeted surveillance was conducted on 416 wild birds offered for sale in in live bird markets (LBMs) and roadside trading points in northern Egypt, mainly in Damietta and Port Said. Of these, 118 birds showing mild clinical signs were examined post-mortem and lung and tracheal tissues were collected, while oropharyngeal and cloacal swabs were collected from apparently healthy birds. Avian influenza virus was detected by RT-qPCR in 22 wild birds, all from tissue samples, whereas all swabs from apparently healthy birds were negative. Waterfowl accounted for 16 of the 22 positive birds (72.7%), with Eurasian teal showing the lowest Ct values (21-25). Phylogenetic and whole-genome analyses showed that the sequenced wild-bird viruses clustered within the recently emerged EA-2024-DI.2.1 sub-lineage and were closely related to contemporary European viruses. Compared with the EA-2021-AB genotype currently circulating in Egyptian poultry, the EA-2024-DI.2.1 viruses showed several HA amino acid differences, including A83D, L104M and T195A. These findings provide evidence for the introduction of EA-2024-DI.2.1 into Egypt through migratory wild birds and highlight the importance of continued genomic surveillance at the wild bird domestic poultry interface and antigenic evaluation against vaccines currently used in Egypt.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

the British Council International Science Partnerships Fund (ISPF), UK, grant number 1203757062

the Science, Technology & Innovation Funding Authority (STDF), Egypt., project ID 50185

Source: 

Link: https://doi.org/10.64898/2026.09.12.750890

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Detection of Highly Pathogenic Avian #Influenza #H5N1 Virus in #Cat and #Rats during #Outbreak in Backyard #Poultry, #USA, 2025

 

Abstract

In 2025, highly pathogenic avian influenza A(H5N1) virus was detected in a poultry flock in Illinois, USA. Quantitative reverse transcription PCR, sequencing, and histopathology on cat and rat samples from the farm showed multiple positive tissues and high sequence identity to an avian isolate. Small mammals might contribute to H5N1 transmission.

Source: 

Link: https://doi.org/10.3201/eid3210.260418

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Detection of #Divergent Highly Pathogenic Avian #Influenza #H5N1 Clade 2.3.4.4b Virus, São Paulo, #Brazil, 2025

 

Abstract

In 2025, we detected highly pathogenic avian influenza H5N1 virus in dead waterfowl at Ibirapuera Park, São Paulo, Brazil. Genomic characterization indicated a reassortant virus that emerged from locally circulating low pathogenicity avian influenza viruses and highly pathogenic North American lineages. Our results highlight cross-species transmission risk and underscore the need for enhanced surveillance.

Source: 

Link: https://doi.org/10.3201/eid3210.260723

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Experimental Highly Pathogenic Avian #Influenza #H5N1 Clade 2.3.4.4b Virus #Infection in #Alpacas, 2026

 

Abstract

Highly pathogenic avian influenza (HPAI) A(H5N1) clade 2.3.4.4b virus continues to spread globally and sporadically transmits from avian reservoirs to mammalian hosts. In May 2024, H5N1 infections in young goats and alpacas in the United States were reported. Nevertheless, the overall susceptibility of camelids to clade 2.3.4.4b virus remains unclear. We conducted a controlled experimental infection study in 6 alpacas, assessing clinical signs, viral shedding, tissue distribution, and serologic responses after intranasal inoculation with HPAI H5N1 genotype B3.13 virus. Observed illness was generally mild; body temperature increased slightly and food intake reduced for up to 3 days postinfection. We detected viral RNA in nasal swab samples and confirmed infectious HPAI H5N1 virus. Immunohistochemistry and RNA in situ hybridization detected virus only in the nasopharyngeal tonsil and nasal conchae at 4 days postinfection. Our findings suggest alpacas are susceptible to productive H5N1 infection, highlighting implications for livestock surveillance and biosecurity in regions with ongoing circulation.

Source: 

Link: https://doi.org/10.3201/eid3210.260491

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Respiratory #pandemic #risk in the #Anthropocene: A #OneHealth #framework and #GISRS+ agenda

 

Highlights

    • Respiratory pandemics are now a structural feature of the Anthropocene.

    • H5Nx and SARS-related CoVs are identified as leading pandemic candidates.

    • A geographic mismatch exists between spillover risk and surveillance.

    • A multidimensional GISRS+ agenda is proposed for proactive One Health.

Abstract

Recent epidemics and pandemics caused by respiratory viruses, alongside the animal panzootic spread of highly pathogenic avian influenza A(H5Nx), have become a structural feature of the Anthropocene, yet responses remain largely reactive. This review integrates findings from WHO's Global Influenza Surveillance and Response System (GISRS) and related surveillance data (2000–2024), epidemiological studies of influenza A virus, SARS-CoV, MERS-CoV, SARS-CoV-2, and H5Nx, and One Health literature. We examine major groups of respiratory viruses and identify mismatches between risk and surveillance by focusing on spillover potential from animal hosts, human-to-human transmission and its controllability, and Anthropocene characteristics that increase epidemic risk. The analysis indicated that SARS-related coronaviruses and influenza A viruses, particularly H5Nx, are among the leading candidates based on currently available evidence because they have large reservoirs in animal hosts and spillover to humans is highly probable. The previous presymptomatic spread of SARS-CoV-2 and recent mammalian adaptation in H5N1 clade 2.3.4.4b highlight limitations of the traditional symptom-based and pathogen-specific surveillance system. Spillover events tend to occur in tropical and subtropical regions in low- and middle-income countries, but most genomic surveillance is in high-income countries. We propose interventions that address the upstream, midstream, downstream processes of epidemics. Upstream interventions are primary prevention measures related to land use, livestock, wildlife, and urban environments; midstream interventions are GISRS+-based pathogen-agnostic genomic and metagenomic early warning systems triggered by One Health; and downstream interventions include vaccines, antivirals, non-pharmaceutical interventions, and engineering with equity-centred global governance and sustainable financing.

Source: 

Link: https://doi.org/10.1016/j.onehlt.2026.101553

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

Backyard captive birds in Los Ríos Region.

Source: 

Link: https://wahis.woah.org/#/in-review/7819

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Establishment of an avian #influenza #surveillance program in #Australia's largest #river basin

 

Abstract

To-date Australia has had mostly coastal occurrences in a small but growing number of species of high pathogenicity avian influenza (HPAI) H5N1 clade 2.3.4.4b. The potential impacts of expected spread are the focus of significant preparation activities. Here we report on early surveillance undertaken in 2025-26 in the Murray-Darling Basin, Australia's largest river system, which contains internationally important wetlands that support large multi-species aggregations of waterbirds vulnerable to mass mortality. We detected two low pathogenicity avian influenza (LPAI) viruses of Australian origin in wild waterbirds. Ongoing surveillance will aid in early detection and rapid response in the case of a major inland outbreak of H5N1.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

Department of Climate Change, Energy, the Environment and Water

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.09.09.750291v1

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Elicitation of Potent #H5N1 - and #H7N9-Neutralizing #Antibody Responses in Rh. Macaques by Sequential Heterologous #Vaccination with #mRNA and Adenoviral Vectors Encoding Full-Length Hemagglutinins

 

Abstract

Highly pathogenic avian influenza (HPAI) represents an enormous pandemic risk amid the ongoing H5N1 panzootic. HPAI, defined by its high lethality in domestic poultry, includes the influenza A virus (IAV) H5N1 and H7N9 subtypes and has a 40–50% case fatality rate in humans. To facilitate the development of efficacious HPAI vaccination regimens and isolation of HPAI-neutralizing monoclonal antibodies (nmAbs) for prophylactic and therapeutic use, we performed a proof-of-concept pilot study wherein we developed an array of mRNA and adenovirus-vectored vaccines encoding HPAI hemagglutinins (HAs) and then assessed their immunogenicity in IAV-naïve Indian rhesus macaques (RMs). All RMs developed binding IgG recognizing both HPAI HAs. HPAI-nAbs were detected in RMs vaccinated with full-length HAs, but not in RMs vaccinated with HA stems alone. Potent HPAI neutralization activity was observed in two animals with serum ID50 titers of ~1:100,000 against H5N1 and ~1:50,000 against H7N9. Most RMs developed cross-reactive IgG recognizing the HAs of additional IAV subtypes, and HA-specific B cells were readily identifiable in vaccinee PBMCs by flow cytometric analysis. The results of our pilot study suggest that elicitation of potent HPAI-nAb responses is enhanced by vaccination with the HA head domain and that vaccination with the HA stem alone tends to elicit binding non-nAbs. Furthermore, use of our fluorophore-conjugated HA probes to identify HA-specific B cells could enable HPAI-nmAb isolation. Collectively, our findings could facilitate the development of novel vaccines and nmAb therapeutics leveraging the superior neutralization potency of HA head-specific Abs to prevent and treat HPAI infections in humans.

Source: 

Link: https://www.mdpi.com/1999-4915/18/9/981

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Sex differences in #vaccine-induced #neuraminidase cross-recognition impact #H5N1 #dissemination to the lower respiratory tract in mice

 

Abstract

H5N1 vaccines have been poorly immunogenic in humans, creating a challenge for vaccine development. Seasonal influenza vaccines offer some cross-protection against H5N1, but there has been no consideration of whether protection differs between the sexes. We investigated sex differences in antibody responses following receipt of either beta-propiolactone inactivated whole virus H1N1 or H5N1 (LAIV backbone) vaccines in C57BL/6 mice. Using systems serology assays, vaccination induced strong homologous and heterologous antibody responses, with females generating greater IgG titers than males against whole virus H1N1 and H5N1, which was primarily mediated by greater IgG responses to neuraminidase (NA) than hemagglutinin (HA) protein. Cross-reactive H5N1 IgG titers were greater among H1N1-vaccinated females, and primarily mediated by greater N1-specific IgG titers. IgG2b and IgG2c were the primary antibody isotypes generated in response to these vaccines, with females having greater IgG2b titers and enhanced binding to FcγRIV for avian and human NA than males following either homologous or heterologous vaccination. Antibody-dependent complement deposition was measured as an FcR-mediated non-neutralizing response against HA and NA and was more robust among H1N1 and H5N1 vaccinated females than their male counterparts in response to homologous HA only. Vaccinated females tended to have greater neutralizing antibody titers than males against the homologous vaccine strain, with limited cross-neutralizing antibodies detected in either sexes. Neuraminidase inhibition titers were greater in vaccinated females than males against the heterologous virus following H1N1 vaccination and against both the vaccine and heterologous viruses following H5N1 vaccination. When H1N1 and H5N1 vaccinated mice were challenged with a lethal dose of A/Texas/37/2024 H5N1, all H5N1 vaccinated mice were protected, regardless of sex. Among H1N1 vaccinated mice, while both sexes were protected against disease, H1N1 vaccinated females restricted virus to the upper respiratory tract and had lower pulmonary virus titers than males at 3 days post challenge. These findings highlight that sex differences in vaccine-induced NA-specific antibody responses are associated with differential respiratory dissemination of H5N1 and that sex should be considered in studies of vaccine-induced cross-reactive influenza immunity.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

NIH/NIAID Johns Hopkins Center of Excellence for Influenza Research and Response, 75N93021C00045

Richard Eliasberg Family Foundation

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.05.26.728011v3

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Lessons Learned During 2024‒25 Highly Pathogenic Avian #Influenza #H5N1 Virus #Outbreak Response in #USA: Experience of State and Local Public Health Departments

 

Abstract

Objectives. 

To describe challenges and lessons learned during state and local health department responses to the 2024‒2025 highly pathogenic avian influenza A(H5N1) outbreaks.

Methods. 

We conducted semistructured interviews from August to November 2025 with Department of Health and Agriculture staff from states with confirmed or probable A(H5N1) human cases. We conducted 15 total interviews with 37 participants from 10 US states. Interview transcripts were inductively and deductively coded to identify generalizable lessons that might improve future outbreak response efforts.

Results. 

Key themes included difficulty accessing farms and reaching at-risk populations; lack of sufficient guidelines for proactively responding to zoonotic outbreaks that could have human health implications; the importance of maintaining preparedness planning, capacity, and infrastructure; and uncertainty around future capacity to respond to outbreaks because of resource constraints and changes in federal leadership.

Conclusions. 

Although this study focused on responses to A(H5N1) outbreaks, the findings are indicative of the nation’s overall readiness for biological threats. Prioritization of capacity building for infectious disease outbreaks, including robust health department funding to support continued disease surveillance, is critical to prevent more widespread transmission. 

(Am J Public Health. Published online ahead of print September 3, 2026:e1–e7. https://doi.org/10.2105/AJPH.2026.308656)

Source: 

Link: https://ajph.aphapublications.org/doi/10.2105/AJPH.2026.308656

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Experimental #reproduction numbers disentangle #vaccine effects on susceptibility and infectiousness during #H5N1 #transmission in #geese

 

Abstract

Vaccination against high pathogenicity avian influenza virus (HPAIV) is increasingly used to protect poultry, but vaccine performance is commonly inferred from clinical protection and virus shedding rather than measured transmission. We asked whether reproduction numbers from controlled transmission experiments can quantify how vaccination changes susceptibility and infectiousness. Domestic geese were prime-boost vaccinated with an H5 clade 2.3.4.4b RNA-replicon vaccine and challenged with homologous HPAIV H5N1. Replicated seeder-sentinel groups represented transmission among unvaccinated animals, to vaccinated contacts, and from vaccinated breakthrough-infected animals. Vaccinated directly challenged geese remained clinically protected although all became RT-qPCR-positive. Estimated reproduction numbers were R0=4.7 (95% CI, 2.8-8.0) among unvaccinated geese, Rs=2.6 (1.6-4.5) for transmission to vaccinated contacts, Ri=3.7 (2.0-6.8) for transmission from vaccinated infected geese, and Rvacc=2.0 (0.8-4.9) for a fully vaccinated population. Vaccination reduced transmission but did not reduce the point estimate for Rvacc below one under these intensive exposure conditions. Vaccinated infected geese also shed substantially less viral RNA, whereas the estimated reduction in infectiousness was more modest, indicating that RNA shedding alone may not reliably predict transmission reduction. Experimental reproduction numbers therefore provide a direct population-level complement to conventional vaccine endpoints and separate effects on susceptibility from effects on onward transmission.

Competing Interest Statement

Christophe Cazaban is an employee of CEVA Santé Animale, which provided the experimental vaccine used in this study. The remaining authors declare no competing interests.

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.09.02.748824v1

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#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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