Mice immunized with #N1 NA in a single cycle infectious virus or in a recombinant nanoparticle #vaccine are protected against lethal challenge with HPAI #H5N1 influenza

 

Abstract

The recent spillover of highly pathogenic (HP) H5N1 clade 2.3.4.4b into dairy cattle and other mammalian species has been concerning. Vaccine candidates that can be rapidly synthesized and implemented are key countermeasures for protecting the human population against emerging pathogens. Here we examine the use of a pH1N1 virus lacking the genetic material for hemagglutinin (HA), limiting the infection to a single cycle (sciIAV) or Cobalt lipid-porphyrin nanoparticles decorated with neuraminidase (NA) of HPAI H5N1 (N1-CoPoP) as vaccine candidates. C57BL/6 mice that were inoculated intranasally with a single dose of pH1N1 sciIAV did not differ in serum NA antibody compared to uninoculated mice. However, mice that were inoculated intramuscularly with the N1-CoPoP alone or in combination with pH1N1 sciIAV had increased N1 IgG antibodies. Upon lethal challenge with HPAIV H5N1, all mice inoculated with either pH1N1 sciIAV or N1-CoPoP were protected from weight loss, unlike unvaccinated mice with substantial body weight losses that succumb to viral infection between 7 and 10 days post infection (dpi). Both pH1N1 sciIAV and N1-CoPoP immunization minimized viral infection such that only one mouse receiving pH1N1 sciIAV had detectable viral titer in the lungs at 4 dpi. By 6 dpi, no mouse inoculated with pH1N1 sciIAV and/or N1-CoPoP had detectable virus in nasal turbinates, lungs or the brain, unlike the high viral titers found in uninoculated mice. Both pH1N1 sciIAV and N1-CoPoP were protective and should be investigated further as alternative vaccine candidates.

Competing Interest Statement

J.F.L. holds interest in POP Biotechnologies. Other authors declare no competing interests.

Funder Information Declared

American Lung Association, https://ror.org/01p3rh655

Texas Biomedical Research Institute

Douglass Foundation

Source: 

Link:  https://doi.org/10.64898/2026.10.11.758125

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

 

{Click on Image to Enlarge}

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By caroline legg - This image has been extracted from another file, CC BY 2.0, https://commons.wikimedia.org/w/index.php?curid=151715256

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A wild Eurasian buzzard (common buzzard) in the Južno-Banatski Region.

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Source: 

Link: https://wahis.woah.org/#/in-review/7899

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#Evidence of Exposure to Highly Pathogenic Avian #Influenza #H5 Viruses in East #Greenland Polar #Bears

 

Abstract

We detected influenza A virus antibodies in plasma collected from East Greenland polar bears during subsistence hunts in 2024 (3/14 [21%]) and 2025 (6/14 [43%]). Four bears from 2025 had antibodies for the globally emerging highly pathogenic avian influenza virus H5 clade 2.3.4.4b, consistent with survival after exposure.

Source: 

Link: https://doi.org/10.3201/eid3211.261050

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

 

{Extracts}

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{Piura Region. Laying hen farm with a total flock of 5,800 birds}

    ° The National Agricultural Health Service (SENASA) within the framework of its epidemiological surveillance responds to reports of suspected animal diseases. 

    ° It has identified an outbreak of highly pathogenic avian influenza in poultry (laying hens), which exhibited respiratory and neurological signs. 

    ° Real-time PCR confirmed the presence of the H5N1 avian influenza virus, prompting the immediate implementation of quarantine measures and an epidemiological investigation. 

    ° All birds were culled, and the epidemiological unit was cleaned and disinfected; in addition, surveillance around the outbreak was conducted to detect possible cases.

(...)

Source: 

Link: https://wahis.woah.org/#/in-review/7894

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#Antiviral Susceptibility of Clade 2.3.4.4b #H5N1 and #H5N5 #Influenza Viruses Detected in #Birds in #Russia During 2021–2022

 

Abstract

In this study, we aimed to analyze the antiviral susceptibility of clade 2.3.4.4b H5N1 and H5N5 influenza viruses detected in Russia during 2021–2022. During this period, we investigated 40 avian influenza outbreaks in wild and domestic birds, isolating 109 H5N1 and 9 H5N5 strains. Using a genetic approach, we analyzed the presence of markers associated with reduced susceptibility to baloxavir and M2 blockers, as well as markers of reduced inhibition by neuraminidase inhibitors (NAIs). Additionally, the isolated strains were tested in a functional assay to evaluate the inhibitory activity of oseltamivir, zanamivir, and peramivir against viral neuraminidase. None of the isolates harbored genetic markers of reduced susceptibility to M2 blockers and baloxavir or reduced inhibition by NAIs. Functional assay showed that the median IC50 values of oseltamivir, zanamivir, and peramivir were 1.73, 0.49, and 0.16 nM for the H5N1 subtype, and 0.65, 1.13, and 0.12 nM for the H5N5 subtype, respectively. None of the tested strains demonstrated a ≥10-fold increase in NAI IC50 values compared to the corresponding subtype medians, and were thus classified as having a normal level of inhibition. The median IC50 values of the NAIs determined for the tested avian viruses were comparable to those of a susceptible seasonal A(H1N1)pdm09 strain, except for a slight reduction in oseltamivir activity against H5N1 viruses (4.3-fold) and zanamivir activity against H5N5 viruses (3.4-fold). Our study revealed a group of H5N1 viruses whose NA belonged to the ea5.1 genetic subclade, characterized by NA-Y253H and T452I amino acid substitutions, which exhibited a 28.8-fold decrease in oseltamivir IC50 values compared to the subtype median. These strains were detected in the European and Ural regions of Russia between May 2022 and January 2023, with no subsequent detections in the available surveillance data. To the best of our knowledge, such strains have not been identified outside Russia.

Source: 

Link: https://doi.org/10.3390/v18101126

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

{Excerpts}

(...)

{Vlaanderen Region} 

    ° The birds in the infected aviary have been euthanized (Somateria mollissima, Anas bernieri, Lophodytes cucullatus, Mergellus albellus, brasiliensis brasiliensis, Spatula hottentota, Anas melleri, Aix galericulata) . 

    ° The other birds have not been culled but are being monitored (derogation from Regulation 2020/687, Article 13.2.d) 05/10/2026 

    ° Birds in other aviaries (ibises and geese) were showing symptoms and tested positive for the H5N1 virus. It was therefore decided to euthanise all the animals.

    ° The captive birds in the two infected aviaries were euthanized, as were the three hens in an uninfected aviary. 

    ° The other birds were not culled but are being monitored (derogation from Regulation 2020/687, Article 13.2.d: animals of high genetic, cultural or educational value, duly justified). ; 

    ° PRIMARY OUTBREAK (Tongeren: secondary outbreak linked to the purchase of ducks in Balen)

(...)

Source: 

Link: https://wahis.woah.org/#/in-review/7868

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The #mammalian-adaptive #PB2-E627K substitution preserves viral fitness of clade 2.3.4.4b #H5N1 HPAIV in #birds

 

Abstract

Since emerging in 2020, clade 2.3.4.4b H5N1 high pathogenicity avian influenza virus (HPAIV) has disseminated globally, causing substantial infection and mortality in wild birds and poultry. Additionally, numerous spill-over events into mammals have occurred, including mass mortalities and sporadic human infections. Such events can drive the acquisition of mammalian-adaptive mutations, which further increase the risk to humans; the most well characterised mutation is the glutamate to lysine change at amino acid position 627 in the polymerase basic 2 protein (PB2-627K). Across avian influenza viruses, PB2-627K enhances polymerase activity and replication in mammalian cells, increasing zoonotic and pandemic potential. However, bioinformatic analyses indicate that PB2-627K remains rare among clade 2.3.4.4b H5N1 viruses circulating in avian populations. Here, we investigated the impact of PB2-627K on viral fitness in avian hosts to assess the potential for mammalian-adapted viruses to re-establish in birds, mimicking infection of avian species following scavenging on mammalian species where PB2-627K has already emerged. Using a representative H5N1 virus (European genotype AB), PB2-627K increased polymerase activity and replication in human cells without compromising replication in avian cells. A mammalian-derived PB2-627K H5N1 isolate from a fox exhibited comparable replication kinetics and transmission efficiency in chickens and ducks to a closely related PB2-627E virus. Notably, PB2-627K remained genetically stable at consensus level following infection and transmission in both avian hosts. These findings demonstrate that mammalian-adaptive mutations acquired during spill-over can be maintained in avian populations, potentially elevating zoonotic risk and underscoring the importance of surveillance for such mutations in birds.

Source: 

Link: https://doi.org/10.64898/2026.10.06.757006

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

 

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A wild Greylag Goose in Nicosia Region.

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Source: 

Link: https://wahis.woah.org/#/in-review/7864

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

 

{Excerpt}

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A backyard poultry farm in Araucanía Region.

(...)

Source: 

Link: https://wahis.woah.org/#/in-review/7872

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

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{Otdar Mean Chey} 

    On 20 September 2026, an outbreak investigation team visited a backyard poultry farm following reports of illness and mortality suspected to be caused by Avian Influenza (AI). 

    A total of three chicken and one duck samples were collected and submitted to NAHPRI/GDAHP for testing of Avian Influenza (H5N1). 

    And On 23 September 2026, laboratory results confirmed that all four samples tested positive for Avian Influenza (H5N1). 

    Additionally, in the same area, one human case of Avian Influenza (H5N1) was confirmed by the Ministry of Health on 27 September 2026.

(...)

Source: 

Link: https://wahis.woah.org/#/in-review/7875

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#Antibodies targeting a conserved cryptic epitope at the #influenza hemagglutinin head-stem interface via distinct binding modes

 

Abstract

Influenza A virus continues to pose pandemic threats, as demonstrated by the recent global spread of highly pathogenic H5N1 strains. Consequently, the development and characterization of vaccines targeting zoonotic influenza subtypes have become a major focus of the field. In this study, we characterize two broadly reactive antibodies previously isolated from H5N1 vaccinees. Although they have distinct immunoglobulin germline gene usage and binding modes, cryo-EM analysis shows that both antibodies share a highly conserved cryptic epitope at the interface of the hemagglutinin (HA) head and stem domains. The antigenicity of this epitope is influenced by natural amino acid variation at residue 293 of HA subunit 1, and its access is facilitated by acid-induced conformational change of HA. Nevertheless, both antibodies are non-neutralizing and possess only marginal protective efficacy against seasonal and H5N1 viruses in vivo, thus representing suboptimal vaccine responses. Overall, our findings expand the interactions of cross-reactive antibodies with an under-characterized HA epitope and provide insights for next-generation influenza vaccine design.

Competing Interest Statement

N.C.W. consults for HeliXon. All authors declare no other competing interests.

Funder Information Declared

Research Grants Council of the Hong Kong Special Administrative Region, China, HKU C7053-24G

Health and Medical Research Fund, no. 24230352

NIH/NIGMS, GM158411

Vallee Scholars Program

Source: 

Link: https://doi.org/10.64898/2026.09.24.754278

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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://doi.org/10.64898/2026.09.09.750291

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Cross-clade #protection against #human #H5N1 isolates by a clade 2.3.4.4b HA #mRNA #vaccine in mice

 

Abstract

The recent spread of clade 2.3.4.4b H5N1 high pathogenicity avian influenza (HPAI) viruses into mammals, despite limited human infections to date, has raised serious public health concerns and highlights the need for rapidly deployable vaccines, such as mRNA-based platforms, to strengthen pandemic preparedness. Here, we evaluated the effectiveness of an mRNA vaccine encoding the HA of NIID-002, a WHO-recommended H5 candidate vaccine virus (CVV) derived from A/Ezo red fox/Hokkaido/1/2022 (clade 2.3.4.4b) against A/Texas/37/2024 (TX37; clade 2.3.4.4b) and A/Cambodia/2311257/2023 (Cam23; clade 2.3.2.1e). The mRNA was formulated with ssPalmO, a low-inflammatory self-degradable ionizable lipid nanoparticle (LNP). BALB/c mice were immunized intramuscularly twice with the mRNA-LNP vaccine containing either 1 μg or 10 μg of H5 HA mRNA. After boosting, strong, dose-dependent serum IgG responses against NIID-002 HA were detected by ELISA. The mice were then challenged with a lethal dose of homologous TX37 or heterologous Cam23. All mice in the 10-μg group survived both challenges, demonstrating robust cross-clade protection. In the 1-μg group, complete protection without significant body weight loss was observed against TX37, whereas partial protection was observed following Cam23 challenge. Viral titers were significantly reduced in multiple tissues of the vaccinated mice compared to the unvaccinated controls. Our findings demonstrate that the NIID-002-HA mRNA vaccine confers protection against homologous and heterologous zoonotic H5N1 strains in a mouse model. This low-inflammatory ssPalmO-LNP platform thus supports safe, rapid vaccine development against emerging H5N1 viruses with pandemic potential.

Source: 

Link: https://doi.org/10.1016/j.vaccine.2026.129215

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

{Click on Image to Enlarge}

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{By Giacomo Cimino (@giacomociminoph) - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=200731939}

{Extracts}

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    ° In accordance with the WOAH Terrestrial Animal Health Code, Article 10.4.1, point 4, this outbreak does not change the disease-free status of Sweden as these are wild birds or birds kept in a single household, and therefore do not fall within the WOAH definition of poultry.

    ° {Kristianstad Region}. A Grey heron was found dead. It was sent to the Swedish Veterinary Agency for laboratory analysis as part of the national surveillance program for avian influenza.

(...)

Source: 

Link: https://wahis.woah.org/#/in-review/7871

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

 {Extracts}

{By Estormiz - Own work, CC0, https://commons.wikimedia.org/w/index.php?curid=90634774}

{Click on Image to Enlarge}

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(...)

    ° According to article 10.4.1.4 of the Terrestrial Animal Health Code, Member Countries should not impose bans on the trade in poultry commodities in response to notification on the presence of any influenza A virus in birds other than poultry.

    ° Nine Wild Common pheasants in Guldborgsund area.

(...)

Source: 

Link: https://wahis.woah.org/#/in-review/7870

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

 

{Excerpts}

(...)

    ° On 18 September 2026, Cologne Zoological Garden received 28 birds from an EU Member State. 

    ° These birds were housed in the zoo’s quarantine facility. 

    ° Current investigations suggest that the introduction of avian influenza (HPAI H5N1) occurred as a result of the movement of these animals. 

    ° Only birds in the quarantine facility are affected by avian influenza.

    ° {Species involved: Mandarin Duck (WILD), Anatidae (unidentified) (WILD), Anserinae (unidentified) (WILD), Greater Scaup (WILD), Hooded Merganser (WILD), Wood Duck (WILD), Smew (WILD), Swan Goose (WILD)}

(...)

Source: 

Link: https://wahis.woah.org/#/in-review/7860

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Avian #Influenza #Report: September 20 - 26 '26 (Wk 39) (HK CHP, Sept. 29 '26): 1 New #H5N1 Human Case in #Cambodia, 2 New #H9N2 Cases in #China

 

{Excerpts}

(...)

    ° Avian influenza A(H5N1)

        § Oddar Meanchey Province:

            - The case involved a 49-year-old man.

            - He has been isolated in the hospital and is receiving intensive medical  care. 

            - The patient worked at a farm and had direct contact with sick and dead chickens which tested positive for avian influenza A(H5N1) virus.

(...)

    ° Avian influenza A(H9N2):

        § Guangdong Province:

            - A one-year-old girl with onset on September 7, 2026.

        § Henan Province:

            - A one-year-old girl with onset on August 30, 2026.

(...)

Source: 

Link: https://www.chp.gov.hk/files/pdf/2026_avian_influenza_report_vol22_wk39.pdf

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In silico analysis of #pH stabilising #mutations of #hemagglutinin of #influenza A virus #H5N1 clade 2.3.4.4b

 

Abstract

Highly pathogenic avian influenza A(H5N1) viruses are expanding their host range among mammals, raising concerns about their pandemic potential. Building on recently published deep mutational scanning data, we show that hemagglutinin retains structural plasticity to increase acid stability through independent mechanisms, including modulation of electrostatic interactions, hydrogen-bonding networks and hydrophobic packing that may facilitate human adaptation. These findings illustrate how structural analyses can strengthen genomic surveillance for pandemic risk assessment.

Source: 

Link: https://doi.org/10.1038/s44298-026-00236-y

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Highly Pathogenic Avian #Influenza Viruses #H5N1 and #H5N5 in Red #Foxes (Vulpes vulpes) in #Norway during 2022-2024

 

Abstract

Since 2020, highly pathogenic avian influenza (HPAI) A(H5Nx) clade 2.3.4.4b viruses have spread globally, causing extensive outbreaks in domestic and wild birds. Increased circulation has resulted in frequent spillover to mammals, and occasional mammal-to-mammal transmission. Although human infections remain rare, the zoonotic potential of these viruses continues to be a public health concern. We investigated six cases of HPAI in red foxes (Vulpes vulpes) in Norway during 2022-2024 and identified infections with H5N1 and H5N5 viruses. Pathological and virological investigations demonstrated systemic infection, with prominent lesions in the brain and/or lungs. Phylogenetic analyses showed high similarity between viruses detected in foxes and those concurrently circulating in wild birds. The mammalian adaptation marker PB2:E627K was identified in one H5N1 virus and as a minority variant in a second H5N1 virus.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

Norwegian Veterinary Institute, 12314

Source: 

Link: https://doi.org/10.64898/2026.09.25.754393

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#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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