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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#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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