#Preclinical evaluation of an #mRNA #vaccine developed from the first #human isolate of #bovine #H5N1

 

Highlights

• SM102 and DB-Y ionizable lipids deliver H5 mRNA vaccine with high efficiency and safety

• Vaccine-induced antibody and T cell response protect mice from H5N1 challenge

• Pre-existing H1 immunity does not diminish H5-specific immunogenicity

• Vaccine fully protects chicken against clade 2.3.4.4b/h H5 virus challenge

Summary

Given the global threat posed by H5N1 clade 2.3.4.4b avian influenza, rapid development of effective vaccines is imperative. We design an mRNA vaccine encoding hemagglutinin (HA) from A/Texas/37/2024, the first bovine-to-human strain. In murine models, both wild-type and cleavage-site-modified HA vaccines elicit robust and durable humoral immunity, along with a balanced Th1/Th2 response, conferring complete protection against lethal homologous viral challenge. The vaccine, along with the World Health Organization (WHO)-recommended candidate (A/Astrakhan/3212/2020), elicits cross-clade binding antibody responses and demonstrates improvement against specific clades at a 1 μg dose. Pre-existing H1 immunity does not diminish H5-specific immunogenicity. In avian species, the vaccine also provides full protection against lethal clades (2.3.4.4b and 2.3.4.4h). Formulated with another ionizable lipid, the vaccine elicits responses comparable to benchmark lipid nanoparticles (LNPs) and shows a favorable safety profile in rats. This work establishes a rapidly adaptable mRNA-LNP vaccine prototype for pandemic preparedness against evolving avian influenza threats.

Source: 

Link: https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(26)00119-9?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2666379126001199%3Fshowall%3Dtrue

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Avian #Influenza #Report - From March 29 to April 4, 2026 (Wk 14) (#HK PRC SAR CHP, April 8 '26): 1 #H5N1 case in #Cambodia, 1 #H7H7 case in #Taiwan

{Excerpts}

(...)

1) H5N1

-- Date of report: 31/03/2026 

-- Country: Cambodia 

-- Province / Region: Oddar Meanchey province

-- District / City: Banteay Ampil district 

-- Sex: Male

-- Age: 3 

-- Condition at time of reporting: Hospitalised 

-- Subtype of virus  H5N1 

(...)

2) H7N7

-- Place of occurrence: Taiwan, China

-- No. of cases  (No. of deaths): 1(0)

-- Details:   

- Avian influenza A(H7N7): 

* Central Taiwan: A man in his 70s who works in a poultry farm with onset on March 20, 2026. 

* This is the first locally-acquired human case of avian influenza A(H7N7) reported in Taiwan, China. 

(...)

Source: 

Link: https://www.chp.gov.hk/files/pdf/2026_avian_influenza_report_vol22_wk14.pdf

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

All [Backyard] birds at the site were culled; surveillance measures continue in the control zone. [Region: Libertador General Bernardo O'Higgins]

Source: 

Link: https://wahis.woah.org/#/in-review/7400

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Using an evolutionary epidemiological #model of #pandemics to estimate the #infection #fatality ratio for #humans infected with avian #influenza viruses

 

Abstract

The risk of highly pathogenic avian influenza virus infection to humans is challenging to estimate as many human avian influenza virus (AIV) infections are undetected because infections may be asymptomatic, symptomatic but not tested, and difficult to identify through contact tracing, as human-to-human transmission is rare. We derive equations that consider the evolutionary mechanisms that give rise to pandemics and are parameterized to be consistent with records of past pandemics. We estimate that thousands of human AIV infections occur worldwide in an average year and estimate the infection fatality ratio as 32 deaths per 10,000 infections (95% confidence interval: [9.6, 75]). This estimate is comparable to SARS-CoV-2 during the recent pandemic and higher than seasonal human influenza. We estimate that preventing animal-to-human influenza spillovers would delay pandemic emergence by several years. Preventing human infections with AIV is necessary given the high risk of severe outcomes to individuals and to reduce the risk of pandemics occurring in the future.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

AH was supported by a Natural Sciences and Engineering Research Council of Canada Discovery Grant (RGPIN 023-05905) and a Catalyst Grant: Avian Influenza OneHealth Research, Enhanced tracking of the circulation of and risk from highly pathogenic avian influenza viruses at the human-wildlife interface from the Canadian Institutes of Health Research. JM, ML, and AH were support by an Atlantic Canada Research in the Mathematical Sciences Collaborative Research Group award.

Source: 

Link: https://www.medrxiv.org/content/10.64898/2026.01.21.26344526v2

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

 

A wild Greylag Goose in Kalmyk Region.

Source: 

Link: https://wahis.woah.org/#/in-review/7410

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MF59-adjuvanted A/Astrakhan #influenza #vaccine induces cross-neutralizing #H5N1 #antibodies in #ferrets against circulating clade 2.3.4.4b viruses

 

Abstract

The continued global spread of highly pathogenic avian influenza A(H5N1) viruses, particularly clade 2.3.4.4b, has increased zoonotic spillover risk and underscored the urgency of pandemic preparedness. Human vaccination is a key strategy for mitigating severe disease and limiting transmission, especially in a setting where avian influenza viruses pose a zoonotic threat. We evaluated the immunogenicity of the MF59-adjuvanted, egg-derived A/Astrakhan/3212/2020 (H5N8) influenza vaccine (CBER-RG8A) in ferrets. To assess cross-reactivity, we generated pseudoviruses bearing HA and NA from circulating A(H5N1) 2.3.4.4b viruses, including North American (B1.13 and D1.1) and Eurasian (DI.2) genotypes. Immunogenicity was assessed using hemagglutination inhibition and microneutralization assays. A single dose elicited robust neutralizing titers (GMT ≥ 160), while a second dose increased titers by ≥3.3-fold. Cross-reactivity was maintained across most strains; however, responses were reduced up to 8-fold against strains harboring the A156T HA mutation, which may introduce a glycosylation site at antigenic site B. Limited responses were detected against divergent clades, with modest titers against clade 2.3.2.1a. These findings suggest broad protection induced by the CSL Seqirus pandemic vaccine against contemporary clade 2.3.4.4b A(H5N1) viruses and underscore the value of ferret immunogenicity data in informing strain selection and regulatory preparedness when human clinical data are unavailable.

Source: 

Link: https://www.nature.com/articles/s41541-026-01438-4

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#Bovine #H5N1 #influenza viruses have adapted to more efficiently use #receptors abundant in #cattle

 

Abstract

Sustained mammal-to-mammal transmission of high pathogenicity H5N1avian influenza viruses is reshaping the host range of these pathogens. One of the longest-running mammalian transmission chains involves the B3.13 genotype circulating in U.S. dairy cattle which was detected early in 2024. Genomic analysis revealed selection and rapid fixation of haemagglutinin mutations D104G and V147M. We demonstate, via glycomic profiling, that bovine tissues, including the mammary gland, are enriched in N- and O-linked glycans capped with N-glycolylneuraminic acid (NeuGc), a sialic acid absent in humans and birds, which instead express only N-acetylneuraminic acid (NeuAc). Early cattle H5 viruses poorly recognized NeuGc, but D104G and V147M enabled efficient engagement of both NeuAc- and NeuGc-containing receptors. These mutations enhanced replication in bovine mammary tissue without major attenuation of replication in human lung and primary nasal epithelial cells. NeuGc-driven receptor adaptation therefore promotes viral fitness in cattle while potentially limiting immediate zoonotic risk. Deep mutational scanning further identifies alternative haemagglutinin substitutions that confer NeuGc usage and represent surveillance markers for emerging cattle H5 lineages.

Competing Interest Statement

JDB and BD are inventors on Fred Hutch licensed patents related to deep mutational scanning. JDB consults for Pfizer, GSK, Apriori Bio, and Invivyd.

Funder Information Declared

Medical Research Council, MR/Y03368X/1, MR/R010757/1, MC_UU_0034/2, MC_UU_0034/3

BBSRC, BB/Y007298/1, BB/X006123/1, BB/X006166/1, BBS/E/PI/230002A, BBS/E/PI/230002B

BBSRC, BBS/E/PI/23NB0004, BBS/E/PI/23NB0003, UKRI2253, BB/V004697/1

Defra, SE2227

Royal Society, https://ror.org/03wnrjx87, RGS\R2\242118

Houghton Trust, HT/SPRG/23/04

Flanders, G005323N, G051322N, G010326N

CEIRR, 75N93021C00045

The Rockefeller Foundation, PC-2022-POP-005

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.04.02.715584v1

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#USA, #Wastewater Data for Avian #Influenza #H5 (#CDC, April 3 '26)

 

{Excerpt}

(...)

Time Period: March 22, 2026 - March 28, 2026

-- H5 Detection: 8 site(s) (1.7%)

-- No Detection: 458 site(s) (98.3%)

-- No samples in last week: 105 site(s)

(...)

Source: 

Link: https://www.cdc.gov/nwss/rv/wwd-h5.html

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

{Magallanes y Antártica Chilena} All the birds were culled. At this time, the SAG is on the field implementing all surveillance measures in the control zone.

Source: 

Link: https://wahis.woah.org/#/in-review/7402

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Predicting highly pathogenic avian #influenza #H5N1 #outbreak #risk using extreme #weather and bird #migration data in machine learning models

 

Abstract

Background. 

Climate change is intensifying extreme weather events (EWEs) with potentially profound consequences for zoonotic disease dynamics, yet the mechanisms linking EWEs to highly pathogenic avian influenza (HPAI) H5N1 outbreaks remain poorly characterized. The ongoing H5N1 panzootic, responsible for infection in over 500 avian and mammalian species, as well as nearly 1000 human cases and 477 deaths worldwide, provides a critical opportunity to evaluate how climate conditions shape spillover risk at landscape scales. 

Methods. 

We compiled a county-month dataset of confirmed H5N1 detections across the contiguous United States from 2022 to 2024 and integrated it with satellite-derived climate metrics, storm event data, and wild bird activity data. We trained and validated a gradient boosting machine classifier to predict outbreak risk and characterize predictor relationships. 

Results. 

Our model achieved strong discriminative performance (AUC-ROC = 0.856; AUC-PR = 0.237, representing a 7-fold improvement over chance) and high recall (0.726), supporting its utility as an early warning tool. Human population and temperature-related variables were the most influential predictors: cold temperature shocks and prolonged low temperatures were consistently associated with elevated outbreak risk, likely through enhanced environmental viral persistence, wild bird habitat compression, and allostatic stress-driven immunosuppression in reservoir hosts. Among storm variables, high wind coverage elevated risk, potentially via aerosol dispersal of contaminated particulates, while tornado activity showed an inverse relationship, consistent with documented avoidant behavior in migratory birds. Wild bird reservoir density showed a strong positive monotonic relationship with outbreak risk. 

Conclusions. 

Our analyses demonstrate that routinely available environmental and infection data can be used to predict HPAI outbreak risk at fine spatiotemporal scales. These findings demonstrate the divergent roles of short- versus long-term environmental exposures in HPAI spillover dynamics, as well as the potential for machine learning-based surveillance tools to inform targeted biosecurity interventions and early warning systems.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

This research was supported by a subaward agreement between prime award recipient Boston University (PI: Gregory Wellenius) and the subaward recipient Regents of the University of Colorado (PI: Elise Grover) under the National Institute of Environmental Health Sciences of the National Institutes of Health, Award Number U24ES035309 -01. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Source: 

Link: https://www.medrxiv.org/content/10.64898/2026.03.30.26349797v1

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#Tropism and #Replication Competence of #Cattle #Influenza #H5N1 Genotype B3.13 Virus in #Human Bronchus and #Lung Tissue

 

Abstract

In 2024, influenza A(H5N1) genotype B3.13 viruses emerged from cattle and caused mild spillover infections in humans. Using human bronchus and lung tissue, we evaluated tropism, replication, and pathogenesis of 2 cattle influenza isolates. Those viruses showed moderate replication competence and induced robust proinflammatory responses, suggesting potential risk for human health.

Source: 

Link: https://wwwnc.cdc.gov/eid/article/32/5/25-1926_article

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The emergence and molecular #evolution of #H5N1 #influenza viruses in #USA dairy #cattle

 

Abstract

Prior to 2024, highly pathogenic avian influenza H5N1 clade 2.3.4.4b viruses circulated predominantly in wild birds and poultry. In 2024 and 2025, 2.3.4.4b genotypes B3.13 and D1.1 were detected in United States dairy cattle. Using whole-genome and segment-specific phylodynamic inference, we estimate that B3.13 and D1.1 spilled over from wild birds into dairy cattle in late 2023 and late 2024, respectively. Spillover occurred shortly after the formation of the reassortant genotypes and was followed by months of cryptic transmission prior to detection. We found that both B3.13 and D1.1 evolved at higher rates in cattle relative to birds, primarily due to relaxed purifying selection. Site-specific analyses identified genomic sites under positive selection in cattle relative to birds, indicating adaptation and likely contributing to improved viral fitness after spillover. Intensified genomic surveillance in dairy cattle is essential as population immunity introduces additional selection pressures, with ever-changing risk for human emergence.

Competing Interest Statement

M.A.S. receives contracts from Johnson & Johnson and Gilead Sciences outside the scope of this work. M.U.G.K. received consulting fees from Takeda, Bavaria Nordic, and Google DeepMind for work unrelated to the manuscript.

Funder Information Declared

Fonds voor Wetenschappelijk Onderzoek - Vlaanderen, G051322N, G051323N

UK Medical Research Council/Department for Environment, Food and Rural Affairs (DEFRA) FluTrailMap-One Health consortium, MR/Y03368X/1

Biotechnology and Biological Sciences Research Council (BBSRC)/DEFRA ‘FluTrailMap’ consortium, BB/Y007298/1

Pirbright Institute’s Strategic Program Grants, BBS/E/PI/230002A, BBS/E/PI/230002B

EMBO Installation Grant, 5305

Academy of Medical Sciences Springboard, 1049

Centers of Excellence for Influenza Research and Response, National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH), Department of Health and Human Services, 75N93021C00015, 75N93021C00014

National Institutes of Health, AI135995, AI153044, AI192139

Rockefeller Foundation, PC-2022-POP-005

Health AI Programme from Google.org

Oxford Martin School Programmes in Pandemic Genomics & Digital Pandemic Preparedness

European Union's Horizon Europe, 874850, 101086640

Wellcome Trust, 303666/Z/23/Z, 226052/Z/22/Z, 228186/Z/23/Z

United Kingdom Research and Innovation, APP8583

Medical Research Foundation, MRF-RG-ICCH-2022-100069

UK International Development, 301542-403

Bill & Melinda Gates Foundation, INV-063472, INV-090281

Novo Nordisk Foundation, NNF24OC0094346

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.03.30.713641v1

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Broad #protection against #Influenza A Viruses via an adjuvant-free #mucosal microparticle #vaccine with conserved CD8/CD4 bispecific peptides

 

Abstract

Influenza A viruses (IAVs) cause substantial global morbidity and mortality and are responsible for most known viral pandemics. Their rapid antigenic evolution enables escape from natural and vaccine-induced immunity, requiring annual vaccine reformulation, which offers limited breadth and variable effectiveness. Although a universal influenza vaccine remains a critical objective, most strategies have focused on conserved viral glycoproteins to elicit broadly neutralizing antibodies, with comparatively fewer efforts targeting conserved T cell antigens to achieve cross-subtype protection. Current T cell-based approaches often rely on individual CD8+ epitopes, which are limited by peptide instability, delivery constraints, and dependence on adjuvants. Here, we demonstrate a T cell-focused vaccine strategy that uses evolutionary consensus of IAV M1 and NP from the H1N1 and H3N2 subtypes to predict, map, and screen conserved regions enriched with multiple CD8+ and CD4+ epitopes. We selected the top-performing peptides from immunogenicity screening. We encapsulated them in polylactic-co-glycolic acid microparticles (PLGA-MPs) engineered for selective uptake by APCs and pH-dependent sustained release. Intranasal delivery of this vaccine formulation targeted the primary site of infection and induced robust mucosal immunity without the need for conventional adjuvants. Both human and murine influenza-experienced T cells mounted potent recall responses to the vaccine. In mice, immunization elicited strong CD8+ and CD4+ T cell responses and conferred broad protection against homologous H1N1 and H3N2 as well as heterologous H5N1 IAV subtypes. These findings collectively establish a mucosal, T cell-based vaccine platform that is adjuvant-free and capable of providing broad protection against IAV and other viruses with pandemic potential.

Competing Interest Statement

The authors have declared no competing interest.

Funder Information Declared

DBT-ENDFLU, BT/IN/EU-INF/15/RV/19-20

Source: 

Link: https://www.biorxiv.org/content/10.64898/2026.03.29.715080v1

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

 

This incident is occurring in the Maule Region, in the municipality of San Rafael, on a recreational property where two owners are responsible for the total number of birds reported. All of the birds will be humanely culled, and the carcasses will be buried on the property under strict biosecurity measures.

Source: 

Link: https://wahis.woah.org/#/in-review/7405

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Antiviral activities of multiple #antivirals against highly pathogenic avian #influenza A #H5N1 in vitro and in mice

 

ABSTRACT

In 2024, a bovine H5N1 strain was first isolated from dairy cows in Texas and confirmed to transmit cross-species to humans. Therefore, research on treatments for human infection should be accelerated. In our study, the antiviral effects of baloxavir acid (BXA), oseltamivir carboxylate (OSC), EIDD-1931 (NHC), and ribavirin (RBV) against five H5N1 strains were evaluated in vitro. Cell viability and viral replication were measured to assess the antiviral effects. The results showed that the EC50 of BXA treatment was the lowest. The BXA/NHC and BXA/OSC combination treatments showed more potent inhibitory effects than each monotherapy. The 15 mg/kg baloxavir marboxil (BXM) / 125 mg/kg molnupiravir (MNP) and the 15 mg/kg BXM / 10 mg/kg oseltamivir phosphate (OSP) were tested in BALB/c mice. The mice were inoculated with 10 times the 50% mouse lethal dose (10 MLD50) of bovine H5N1 virus. Treatments began 1-day post-infection (1 dpi) and were administered orally twice daily for 5 or 7 days. Changes in body weight, clinical signs, and survival were monitored; lung and brain tissues were collected for virological, immunological, and histological analyses. Most mice died from severe neurological symptoms. Compared with the 5-day treatment, the 7-day treatment effectively inhibited viral replication and increased survival rates to 50% in BXM, BXM/MNP, and BXM/OSP treatments. Mice treated with BXM/MNP or BXM/OSP combination therapy showed lower viral yields in the lungs than those treated with BXM alone. The results provide a reference for human treatment, and extending the 7-day combination treatment should be considered.

Source: Emerging Microbes and Infections, https://www.tandfonline.com/journals/temi20

Link: https://www.tandfonline.com/doi/full/10.1080/22221751.2026.2645843

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#Cambodia - #Influenza A #H5N1 viruses of high pathogenicity (Inf. with) (non-poultry including wild birds & one #human case) (2017-) - Immediate notification

 

On 26 March 2026, an outbreak investigation team visited a backyard farm following reports of illness and mortality suspected to be caused by Avian Influenza (AI). A total of five samples (three chickens and two ducks) were collected and submitted to NAHPRI/GDAHP for testing of Avian Influenza (H5N1). On 27 March 2026, laboratory results confirmed that three out of five samples (two chickens and one duck) 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 31 March 2026.

Source: 

Link: https://wahis.woah.org/#/in-review/7409

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A Live Attenuated #Vaccine Candidate against Emerging Highly Pathogenic #Cattle-Origin 2.3.4.4b #H5N1 [#Influenza] Viruses

 

Abstract

Influenza viruses present a significant public health risk, causing substantial illness and death in humans each year. Seasonal flu vaccines must be updated regularly, and their effectiveness often decreases due to mismatches with circulating strains. Furthermore, inactivated vaccines do not provide protection against shifted influenza viruses that have the potential to cause a pandemic. The highly pathogenic avian influenza H5N1 clade 2.3.4.4b is prevalent among wild birds worldwide and is causing a multi-state outbreak affecting poultry and dairy cows in the United States (US) since March 2024. In this study, we have generated a NS1 deficient mutant of a low pathogenic version of the cattle-origin human influenza A/Texas/37/2024 H5N1, namely LPhTXdNS1, and validated its safety, immunogenicity, and protection efficacy in a prime vaccination regimen against wild-type (WT) A/Texas/37/2024 H5N1. The attenuation of LPhTXdNS1 in vitro was confirmed by its reduced replication in cultured cells and inability to control IFNβ promoter activation. In C57BL/6J mice, LPhTXdNS1 has reduced viral replication and pathogenicity compared to WT A/Texas/37/2024 H5N1. Notably, LPhTXdNS1 vaccinated mice exhibited high immunogenicity that reach its peak at weeks 3 and 4 post-immunization, leading to robust protection against subsequent lethal challenge with WT A/Texas/37/2024 H5N1. Altogether, we demonstrate that a single dose vaccination with LPhTXdNS1 is safe and able to induce protective immune responses against H5N1. Both safety profile and protection immunity suggest that LPhTXdNS1 holds promise as a potential solution to address the urgent need for an effective vaccine in the event of a pandemic for the treatment of infected animals and humans.

Competing Interest Statement

The A.G.-S. laboratory has received research support from GSK, Pfizer, Senhwa Biosciences, Kenall Manufacturing, Blade Therapeutics, Avimex, Johnson & Johnson, Dynavax, 7Hills Pharma, Pharmamar, ImmunityBio, Accurius, Nanocomposix, Hexamer, N-fold LLC, Model Medicines, Atea Pharma, Applied Biological Laboratories and Merck. A.G.-S. has consulting agreements for the following companies involving cash and/or stock: Castlevax, Amovir, Vivaldi Biosciences, Contrafect, 7Hills Pharma, Avimex, Pagoda, Accurius, Esperovax, Applied Biological Laboratories, Pharmamar, CureLab Oncology, CureLab Veterinary, Synairgen, Paratus, Pfizer and Prosetta. A.G.-S. has been an invited speaker in meeting events organized by Seqirus, Janssen, Abbott, Astrazeneca and NovavaxA.G.-S. is inventor on patents and patent applications on the use of antivirals and vaccines for the treatment and prevention of virus infections and cancer, owned by the Icahn School of Medicine at Mount Sinai, New York. All other authors declare no commercial or financial conflict of interest.

Source: 

Link: https://www.biorxiv.org/content/10.1101/2025.03.28.646033v2

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#USA, #Wastewater Data for Avian #Influenza #H5 (#CDC, March 27 '26)

 

{Excerpt}

(...)

Time Period: March 15, 2026 - March 21, 2026

-- H5 Detection: 9 site(s) (2.0%)

-- No Detection: 436 site(s) (98.0%)

-- No samples in last week: 130 site(s)

(...)

Source: 

Link: https://www.cdc.gov/nwss/rv/wwd-h5.html

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

 

Two wild Canada Geese in the Lounais-Suomen aluehallintovirasto Region.

Source: 

Link: https://wahis.woah.org/#/in-review/7401

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Deciphering #HPAI #Influenza A Virus #H5N1: Molecular Basis of #Pathogenicity, Zoonotic Potential, and Advances in #Vaccination Strategies

 

Abstract

The ongoing panzootic of the highly pathogenic avian influenza (HPAI) H5N1 virus, dominated by clade 2.3.4.4b, constitutes a significant global threat to wildlife, animal health, and public health. Once characterized by sporadic outbreaks, H5N1 has evolved into a sustained, year-round infection with an expanded host range that now includes numerous mammalian species. Its high pathogenicity is primarily driven by the acquisition of a polybasic haemagglutinin cleavage site, enabling systemic viral spread, alongside emerging endothelial and neurotropic properties that contribute to severe disease and high mortality in mammals. Although zoonotic transmission remains limited, H5N1 continues to accumulate mutations associated with mammalian adaptation, particularly within the haemagglutinin and polymerase complex. Notably, recent outbreaks in U.S. dairy cattle highlight the emergence of novel mammalian reservoirs with increased human exposure risk. Concurrently, vaccination strategies are advancing beyond traditional adjuvanted inactivated vaccines toward next-generation platforms, including mRNA and virus-like particle vaccines, designed for rapid deployment and broader immune protection. However, ongoing viral evolution, constrained vaccine availability, and gaps in coordinated surveillance underscore the urgent need for an integrated One Health approach to reduce panzootic risk.

Source: 

Link: https://www.mdpi.com/1999-4915/18/4/410

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