Structural basis for a potent #human neutralizing #antibody targeting a conserved epitope on the #H7 #hemagglutinin head

 

Significance

The high-resolution cryo-EM structure indicates that the human antibody 6Y13 binds strongly to a conserved pan-H7 epitope on the hemagglutinin head, distinct from the receptor-binding site and lateral patch. However, 6Y13 can broadly neutralize H7 viruses, fully protect H7N9-infected mice, and potently block receptor binding through mechanisms, independent of Fc-mediated steric hindrance.

Abstract

Zoonotic H7N9 avian influenza virus infection remains a global concern because of its pandemic potential. Therefore, developing effective antibodies and vaccines against H7N9 is vital for preventing and controlling major outbreaks. Here, we isolated a human VH3-30 gene-encoded antibody, designated 6Y13, from a survivor of H7N9 infection. This antibody recognized the hemagglutinins (HAs) of the representative H7 subtype zoonotic viruses spanning two decades of antigenic evolution and potently neutralized epidemic H7N9 viruses in vitro. Moreover, 6Y13 conferred complete protection in mice against lethal H7N9 challenge in both prophylactic and therapeutic experiments. Structural analysis by cryoelectron microscopy indicated that 6Y13 binds to a unique conserved site on the HA head, distinct from the receptor-binding site and lateral patch. Nevertheless, 6Y13 efficiently blocked viral receptor binding without interfering with HA receptor binding, independent of Fc-mediated steric hindrance. Our findings provide a promising therapeutic candidate against pan-H7 subtype viruses and are beneficial for the design of H7 subtype influenza vaccine immunogens.

Source: Proceedings of the National Academy of Sciences of the United States of America, https://www.pnas.org/doi/10.1073/pnas.2503008122

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

 

{By Diliff - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=1385555}

Following the detection of HPAI H5N1 in a greylag goose found dead near the lake Biel on 4 November 2025, an infected area of 3 km around the three lakes in vicinity of the site of detection has been put in place. Within this area, measures of increased disease awareness, biosecurity and notification obligations have to be followed by poultry owners.

A wild Greylag Goose found dead in Bern Region.

Source: WOAH, https://wahis.woah.org/#/in-review/6985

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

 

{England}

Mixed commercial premises with 32.7k ducks and 11.6k broilers. Samples taken were positive for HPAI H5N1. Birds presented clinical signs of AI prior to testing.

Source: WOAH, https://wahis.woah.org/#/in-review/6987

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#Zoonotic Implications of the Co-Circulation of Clade 2.3.4.4b and 2.3.2.1a #H5N1 Avian #Influenza Viruses in #Nepal in 2023

 

Abstract

Samples collected from two avian influenza outbreaks in Bagmati Province in central Nepal between January and March 2023 were positive for H5N1. Full genomes were generated for both viruses, which revealed that one of the viruses was very similar to clade 2.3.4.4b H5N1 identified in Bangladesh in 2021/2022. The second virus was a reassortant H5N1 virus consisting of four genes (HA, NA, NP, and M) originating from a clade 2.3.2.1a H5N1 and the remaining four genes (NS, PB1, PB2, and PA) originating from a 2.3.4.4b H5N1. Notably, this second virus had a high identity with 2.3.2.1a clade viruses identified in humans and cats in India in 2024–2025. These are the first full genome sequences of H5N1 avian influenza viruses from Nepal and given the recent human infections by 2.3.2.1a H5N1 viruses in the region, these data will be of interest to both public health and veterinary authorities.

Source: Viruses, https://www.mdpi.com/1999-4915/17/11/1481

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An #intranasal adjuvanted, recombinant #influenza A/ #H5 #vaccine primes against diverse #H5N1 clades: a phase I trial

 

Abstract

Mucosal influenza vaccines may provide improved protection against infection and transmission, but their development is hindered by absence of immune correlates of protection. Here, we report a randomized, controlled phase I trial of a recombinant influenza A/H5 (A/Indonesia/05/2005, clade 2.1) hemagglutinin vaccine formulated with a nanoemulsion adjuvant (W805EC). The vaccine is administered intranasally in two doses 28 days apart at three antigen levels. Controls receive unadjuvanted H5 or placebo. Six months later, participants receive an intramuscular boost with unadjuvanted inactivated A/H5N1 (A/Vietnam/1203/2004, clade 1) vaccine. Primary outcomes are solicited and unsolicited adverse events (AEs), laboratory safety abnormalities, medically-attended AEs, potential immune-mediated conditions, new-onset chronic conditions, and serious AEs. All vaccines are well tolerated. After the intranasal series, hemagglutination inhibition and microneutralization responses are minimal. However, adjuvanted H5 recipients show significant increases in mucosal and serum IgG/IgA, surface plasmon resonance antibody binding, memory B and CD4 T cell activity, and antibody-dependent cell-mediated cytotoxicity. Following H5N1 boost, participants mount robust responses across measurements and have microneutralization responses against diverse H5N1 clades (including circulating clade 2.3.4.4b). Findings demonstrate successful mucosal priming and broad cross-clade responses. This intranasal vaccine supports further exploration of mucosal immune biomarkers and may accelerate development of intranasal influenza vaccines. ClinicalTrials.gov registration: NCT05397119

Source: Nature Communications, https://www.nature.com/articles/s41467-025-64686-3

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Rift Valley #fever [#RVFV] - #Mauritania and #Senegal (#WHO, D.O.N., Nov. 6 '25)

 

Situation at a glance

Between 20 September and 30 October 2025, a total of 404 confirmed human cases of Rift Valley fever (RVF), including 42 deaths, were reported by national health authorities in two West African countries: Mauritania and Senegal. 

RVF is a zoonotic disease, which mainly affects animals, but can also infect humans. 

The majority of human infections result from contact with the blood or organs of infected animals, but human infections have also resulted from the bites of infected mosquitoes. 

To date, no human-to-human transmission of RVF has been documented. 

While RVF often leads to severe illness in animals, its impact in humans varies, ranging from mild flu-like symptoms to severe hemorrhagic fever that can be fatal. 

RVF is endemic in both countries, where recurrent outbreaks have been previously reported in both livestock and humans. 

The risk of further spread remains high, especially with environmental conditions favorable to the proliferation of mosquitoes, periods of heavy rains and increased mosquito activity, as well as movements of livestock within country and towards Mali and Gambia for grazing and trade. 

The response to RVF outbreaks requires a One Health approach, based on enhanced collaboration between the human health, animal health and environmental sectors, in both countries and at the regional level. 

WHO, in collaboration with the World Organization for Animal Health (WOAH), and the Food and Agriculture Organization of the United Nations (FAO), currently assesses the overall risk as high at the national levels, moderate at the regional level and low at the global level.

(...)

Source: World Health Organization, https://www.who.int/emergencies/disease-outbreak-news/item/2025-DON584

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#Safety and Immunogenicity of an rVSV #Lassa Fever #Vaccine Candidate

 

Abstract

Background

No vaccine is currently available for Lassa fever, a viral hemorrhagic disease that is estimated to cause thousands of deaths each year in western Africa. A replication-competent recombinant vesicular stomatitis virus–vectored vaccine encoding a Lassa virus (LASV) glycoprotein complex, rVSVΔG-LASV-GPC, has been developed, but data on its safety and immunogenicity are limited.

Methods

In this phase 1, double-blind trial conducted in the United States and Liberia, we randomly assigned healthy adults (18 to 50 years of age) to receive rVSVΔG-LASV-GPC or placebo intramuscularly. Participants received a single vaccine dose of 2×104 plaque-forming units (PFU), 2×105 PFU, 2×106 PFU, or 2×107 PFU or placebo or received two vaccine doses of 2×107 PFU or placebo, within a window of 6 to 20 weeks. The side-effect profile was assessed according to the incidence of solicited and unsolicited adverse events (primary end point). Because Lassa fever can cause sensorineural hearing loss, hearing acuity was measured before and after the injection. Secondary end points were levels of binding antibodies against LASV glycoprotein, neutralizing antibodies, and vaccine vector–derived viral RNA and PFU in plasma, urine, and saliva.

Results

A total of 114 adults were enrolled. No serious vaccine-related adverse events were reported. The vaccine caused minimal local reactions and dose-dependent, mild-to-severe early-onset systemic reactogenicity events that were transient. No hearing loss was detected. All doses induced robust long-lasting cellular and humoral (binding and neutralizing) responses that cross-reacted against common LASV lineages. No infectious vaccine virus particles were found in plasma, urine, or saliva.

Conclusions

The rVSVΔG-LASV-GPC vaccine resulted in transient local and systemic reactogenicity events but no hearing loss or serious adverse events. The vaccine had immunogenicity over a wide dose range in healthy adults in the United States and Liberia. (Funded by the Coalition for Epidemic Preparedness Innovations and the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT04794218; Pan African Clinical Trials Registry number, PACTR2021106625781067.)

Source: The New England Journal of Medicine, https://www.nejm.org/doi/full/10.1056/NEJMoa2501073?query=TOC

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Controlled #human #influenza #infection reveals heterogeneous expulsion of infectious virus into #air

 

Abstract

Influenza virus is transmitted via respiratory expulsions, but detection of infectious virus in such expulsions has been challenging. Here, we describe quantification and genotyping of infectious virus in respiratory particles using a Modular Influenza Sampling Tunnel (MIST). The particles deposit on cell monolayers, enabling culture, quantification, and sequencing of viruses. Concomitantly, water-sensitive paper and fine particle samplers yield respiratory particle counts over a broad size range. Using the MIST, we captured infectious virus from humans experimentally infected with influenza virus on multiple days post-inoculation. The recovered respiratory particles varied in quantity over three orders of magnitude and contained viral genetic variation that was also detected in samples from infected individuals. Expulsion of infectious virus was associated with infectious viral load in saliva and nasopharyngeal swabs and with clinical symptoms. These data reveal the maintenance of viral diversity in expelled aerosols and suggest that heterogeneity among individuals in the magnitude of infectious expulsions may impact forward transmission potential.

Competing Interest Statement

NGR receives funding from Merck, Sanofi, Pfizer, Vaccine Company, Immorna, and consulting fees from Krog &Partners. Merck, CSK is a consultant for Ferring Pharmaceuticals. LCM serves as a consultant for MITRE corporation. None of these funders or consulting agencies were involved in the research described or influenced the studies.

Clinical Trial

NCT05332899

Funding Statement

This work was funded by Flu Lab, NIAID Centers of Excellence for Influenza Research and Response (CEIRR), contract number 75N93021C00017, and internal Emory University funds awarded to NGR. NVM is supported by 1F31AI186480-01. Next generation sequencing services were provided by the Emory NPRC Genomics Core which is supported in part by NIH P51 OD011132. Sequencing data was acquired on an Illumina NovaSeq 6000 funded by NIH S10 OD026799.

Source: MedRxIV, https://www.medrxiv.org/content/10.1101/2025.11.03.25339190v1

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

 

A sudden increased mortality in a commercial turkey flock. Samples were collected and submitted to the Irish Central Veterinary Research Laboratory for avian influenza testing. On 4th November 2025 highly pathogenic avian influenza sub. H5N1 was confirmed by the national reference laboratory.

Source: WOAH, https://wahis.woah.org/#/in-review/6976

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

 

{By Lukasz Lukasik - The uploader on Wikimedia Commons received this from the author/copyright holder., CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=816655}

{Isle of Man}

1 wild bird (common buzzard) was found dead on 27/10/2025. Official samples were taken and tested positive for HPAI H5N1.

Source: WOAH, https://wahis.woah.org/#/in-review/6977

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#Kyasanur Forest #disease: an emerging #arboviral #threat

 

Summary

Kyasanur Forest disease is a neglected tick-borne viral haemorrhagic fever endemic to India's Western Ghats, caused by the Kyasanur Forest disease virus, a flavivirus transmitted by Haemaphysalis spinigera ticks. The virus circulates in a sylvatic cycle among monkeys, rodents, shrews, birds, and ixodid ticks, and is transmitted to humans incidentally via tick bites. Since its discovery in 1957 in Karnataka, Kyasanur Forest disease has spread to other Indian states, driven by deforestation, forest fragmentation, and increased human incursion into wildlife habitats. Clinically, the disease manifests in a biphasic pattern, with haemorrhagic and neurotropic presentations. Although a formalin-inactivated vaccine is available, its efficacy is not promising, and no antivirals have been approved to date. Field reports indicate that mortality in monkeys might serve as an early indicator of forthcoming human outbreaks. The transmission dynamics of Kyasanur Forest disease, diagnostic gap, and ecological complexities present substantial public health challenges. In this Review, we provide an update on Kyasanur Forest disease virus, covering its epidemiology, transmission dynamics, molecular virology, virus–host interactions, immunological responses, animal models, and potential antiviral therapies and vaccines.

Source: Lancet Infectious Diseases, https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(25)00589-4/abstract?rss=yes

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#Transmission of #SARS-CoV-2 between #ferrets in presence of pre-existing #immunity

 

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of coronavirus disease 2019 (COVID-19), is characterized by its high contagiousness. The COVID-19 pandemic has exerted profound impacts on human society. The persistent circulation of SARS-CoV-2 in human populations continues to pose re-exposure risks for both vaccinated individuals and those with prior natural infection. Against this epidemiological background, there is an urgent need to characterize the transmission dynamics of SARS-CoV-2 in the context of pre-existing immunity. Using a ferret infection model, this study systematically addresses critical scientific questions, including viral transmission efficiency, temporal patterns of transmissibility, and the ability of pre-existing immunity to mitigate reinfection and viral shedding. The findings provide robust experimental evidence for elucidating the transmission mechanisms of SARS-CoV-2 and offer scientific insights to inform the rational design of optimized antiviral strategies.

Source: Journal of Virology, https://journals.asm.org/doi/full/10.1128/jvi.01566-25?af=R

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

 

The last outbreak of highly pathogenic avian influenza in poultry in Lubuskie region was confirmed on 11/03/2025. 02/05/2025 is the date of confirmation of the last outbreak in Poland in the spring of 2025.

A turkeys slaughterhouse operation in Lubuskie Region.

Source: WOAH, https://wahis.woah.org/#/in-review/6972

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Inverted #H1 #hemagglutinin nanoparticle #vaccines protect mice against challenges with human #H1N1 and bovine #H5N1 #influenza viruses

 

Abstract

Influenza is a global health concern, causing over 300,000 deaths worldwide annually. Current vaccines and natural infection mainly elicit antibodies against the variable head domain of the hemagglutinin (HA) glycoprotein. While these antibodies are highly neutralizing, the head domain constantly mutates due to selective pressure, causing the immune response to be strain-specific. Targeting the conserved HA stalk domain, however, has been shown to be a promising approach for a broadly protective vaccine. We previously demonstrated that presenting HA in an inverted orientation on virus-like particles (VLPs) significantly enhanced the induction of stalk-directed, cross-reactive antibodies compared to HA presented in a regular orientation. Here, we evaluated the protective efficacy of the inverted HA vaccine (VLP-HAinv) in mice against homologous, heterologous, and heterosubtypic influenza A virus challenges. VLP-HAinv vaccination in mice provided complete protection against homologous and heterologous H1N1 challenges as well as partial protection against a heterosubtypic challenge with bovine H5N1.

Source: npj Vaccines, https://www.nature.com/articles/s41541-025-01276-w

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Iris #Pigmentation Irregularities Following An Avian #Influenza #Outbreak: Implications For Disease #Surveillance & Population Monitoring in a Colonial #Seabird

 

Abstract

Emerging infectious diseases can have catastrophic impacts on wildlife populations, yet identifying individuals that survived exposure, especially when external symptoms are absent, remains challenging. Since 2021, a virulent strain of highly pathogenic avian influenza virus (HPAIV H5N1 clade 2.3.4.4b) has caused unprecedented mortality in wild birds across continents. Northern Gannets (Morus bassanus) are among the species that suffered significant population declines in Europe and North America. At North America's largest gannet colony (Bonaventure Island) dramatic mortality and reproductive failure occurred in 2022. Following this event, researchers noted a subset of gannets displaying irregular iris pigmentation, raising the possibility that this visible change may indicate a lasting effect of infection. Here, we build on earlier observations linking irregular iris pigmentation to HPAIV exposure in gannets using anti-nucleoprotein (NP) and anti-hemagglutinin (H5) antibodies. This provides the first quantitative test of this relationship using serological data and field-based digital photography. Iris irregularities were strongly associated ( ρ = -0.72) with antibodies to NP, supporting the hypothesis that they can indicate past exposure. The likelihood of NP antibody detection increased with iris pigment irregularity - about 50% likelihood at 40% irregularity, 65% at 50%, 77% at 60%, and over 90% above 77% irregularity. Moderate correlations (ρ = 0.30) were observed for H5 antibodies. Our findings provide quantitative support for the hypothesis that iris pigmentation irregularities may serve as a visible, non-invasive marker of past HPAIV exposure in gannets. If validated across colonies and years, iris assessment could offer a rapid tool for tracking population health and recovery following HPAIV outbreaks, enhancing conservation monitoring and disease surveillance.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

Environment and Climate Change Canada, https://ror.org/026ny0e17

Natural Sciences and Engineering Research Council of Canada

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.10.31.685885v1

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#Molnupiravir clinical trial simulation suggests that #PCR underestimates #antiviral #potency against #SARS-CoV-2

 

Abstract

Molnupiravir is an antiviral medicine that induces lethal copying errors during SARS-CoV-2 RNA replication. Molnupiravir reduced hospitalization in one pivotal trial by 50% and had variable effects on reducing viral RNA levels in three separate trials. We used mathematical models to simulate these trials and closely recapitulated their virologic outcomes. Model simulations suggested lower antiviral potency against pre-Omicron SARS-CoV-2 variants than against Omicron. We estimated that in vitro assays underestimated in vivo potency by 6- to 7-fold against Omicron variants. Our model suggested that because polymerase chain reaction detects molnupiravir mutated variants, the true reduction in non-mutated viral RNA was underestimated by approximately 0.4 log10 in the two trials conducted while Omicron variants dominated. Viral area under the curve estimates differed significantly between non-mutated and mutated viral RNA. Our results reinforce past work suggesting that in vitro assays are unreliable for estimating in vivo antiviral drug potency and suggest that virologic endpoints for respiratory virus clinical trials should be catered to the drug mechanism of action.

Source: Journal of Clinical Investigation, https://www.jci.org/articles/view/192052

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

 

A laying hens farm in Sachsen-Anhalt Region.

Source: WOAH, https://wahis.woah.org/#/in-review/6966

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

 

{Di Sanchezn - Opera propria, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=3019282}

Confirmation of HPAI - H5N1 case, at Cygnus olor Port Contanta Dana 55 in the Constanta county.

Source: WOAH, https://wahis.woah.org/#/in-review/6968

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A #cattle-derived #human #H5N1 isolate suppresses innate #immunity despite efficient #replication in human respiratory #organoids

 

Abstract

The H5N1 high pathogenicity avian influenza virus (HPAIV) of clade 2.3.4.4b, which spreads globally via wild birds, has become a major public health concern because it can infect a variety of mammals, including humans. In 2024, infection of dairy cattle with H5N1 HPAIV clade 2.3.4.4b was confirmed in the United States, and subsequent human cases were reported. Although these viruses are highly pathogenic in animal models, human infections have generally been mild, revealing a striking discrepancy. Here, we characterized the cattle-derived human H5N1 isolate A/Texas/37/2024 (TX37-H5N1) using three-dimensional human respiratory organoids derived from induced pluripotent stem (iPS) cells. Despite efficient replication, TX37-H5N1 induced minimal interferon and inflammatory cytokine responses. Bulk and single-cell RNA sequencing revealed reduced STAT1-mediated transcriptional activity in TX37-H5N1-infected organoids compared to the historic H5N1 human isolate A/Vietnam/1203/2004. These findings suggest that TX37-H5N1 fails to trigger the strong innate responses, including robust cytokine production, that are typically associated with severe H5N1 disease and are thought to contribute to cytokine storm-medicated pathogenesis. This attenuated response may help explain the discrepancy between the high pathogenicity of TX37-H5N1 in animal models and its mild clinical presentation in humans. While zoonotic influenza risk is often assessed using cell lines or animal models, our study highlights the value of using human respiratory organoids to evaluate human-specific virus-host interactions. This platform provides a complementary tool for assessing the risk of emerging avian influenza viruses.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

Japan Society for the Promotion of Science, JP24K09264

Japan Agency for Medical Research and Development, JP223fa627005, JP243fa627003h0003, JP24gm1810009, JP223fa627002, JP233fa827018

Japan Agency for Medical Research and Development, JP21gm1610005, JP22gm1610010

Japan Science and Technology Agency, JPMJMS2025

Takeda Science Foundation, https://ror.org/02y123g31

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.11.02.684669v1

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The Nightmare (1781), Detroit Institute of Arts (Henry Fuseli)

 

By Tulip Hysteria / Go to albums - https://www.flickr.com/photos/36417567@N03/32380012237/, CC BY 2.5, https://commons.wikimedia.org/w/index.php?curid=111521078

Source: Wikipedia, https://en.wikipedia.org/wiki/Henry_Fuseli

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