Neutralizing Antibody Response to Influenza A(H5N1) Virus in Dairy Farm Workers, Michigan, USA - PubMed
Since March 2024, highly pathogenic avian influenza A(H5N1) viruses have caused outbreaks in dairy cattle and poultry in the United States, and they continue to spill over into humans. However, data on human immune response to those viruses is limited. We report neutralizing antibody responses in 2 …
Antiviral Susceptibility of Influenza A(H5N1) Clade 2.3.2.1c and 2.3.4.4b Viruses from Humans, 2023-2024 - PubMed
During 2023-2024, highly pathogenic avian influenza A(H5N1) viruses from clade 2.3.2.1c caused human infections in Cambodia and from clade 2.3.4.4b caused human infections in the Americas. We assessed the susceptibility of those viruses to approved and investigational antiviral drugs. Except for 2 v …
Reverse genetics-derived cattle H5N1 virus from Clade 2.3.4.4b shows enhanced systemic infectivity and pathogenicity than an older Clade 1 H5N1 virus in BALB/c mice - PubMed
The newly emerged avian influenza A H5N1 Clade 2.3.4.4b can infect dairy cows and shed live virus in their milk. Sporadic cattle-to-human infections have been reported, highlighting the urgent need to understand its pathogenesis in mammals. Using both non-lactating and lactating BALB/c mice, we exam …
Effect of Prior Influenza A(H1N1)pdm09 Virus Infection on Pathogenesis and Transmission of Human Influenza A(H5N1) Clade 2.3.4.4b Virus in Ferret Model - PubMed
Reports of human infections with influenza A(H5N1) clade 2.3.4.4b viruses associated with outbreaks in dairy cows in the United States underscore the need to assess the potential cross-protection conferred by existing influenza immunity. We serologically evaluated ferrets previously infected with an …
Genome-wide siRNA library screening identifies human host factors that influence the replication of the highly pathogenic H5N1 influenza virus - PubMed
The global dissemination of H5 avian influenza viruses represents a significant threat to both human and animal health. In this study, we conducted a genome-wide siRNA library screening against the highly pathogenic H5N1 influenza virus, leading us to the identification of 457 cellular cofactors (44 …
US dodged a bird flu pandemic in 1957 thanks to eggs and dumb luck – with a new strain spreading fast, will Americans get lucky again?
In recent months, Americans looking for eggs have faced empty shelves in their grocery stores. The escalating threat of avian flu has forced farmers to kill millions of chickens to prevent its spread.
Chief of Infectious Diseases, Dr. Elizabeth Asiago-Reddy gives an update on bird flu (avian influenza). Computational neuroscientist Christopher Gaiteri discusses what research into brain connectivity reveals about dementia and other disorders.
Clade 2.3.4.4b H5N1 neuraminidase has a long stalk, which is in contrast to most highly pathogenic H5N1 viruses circulating between 2002 and 2020 - PubMed
Since 2020, H5N1 highly pathogenic avian influenza (HPAI) viruses of clade 2.3.4.4b have been rapidly spreading in wild birds but have also caused a large number of mammalian infections and more than 70 known human cases. Importantly, this H5N1 clade has also crossed the species barrier into dairy c …
Pathogenicity of Highly Pathogenic Avian Influenza A/H5Nx Viruses in Avian and Murine Models - PubMed
The evolution and adaptation of highly pathogenic avian influenza (HPAI) viruses pose ongoing challenges for animal and public health. We investigated the pathogenic characteristics of the newly emerged H5N1/2022 and H5N8/2022 of clade 2.3.4.4b compared to the previously circulating H5N1/2016 of cla …
Immunity against seasonal H1N1 flu reduces bi | EurekAlert!
Pre-existing immunity against seasonal H1N1 flu might help explain why most reported human cases of H5N1 bird flu in the U.S. have not resulted in lethal outcomes.
Effect of Prior Influenza A(H1N1)pdm09 Virus Infection on Pathogenesis and Transmission of Human Influenza A(H5N1) Clade 2.3.4.4b Virus in Ferret Model
Human monoclonal antibodies that target clade 2.3.4.4b H5N1 hemagglutinin
The highly pathogenic avian influenza H5N1 virus clade 2.3.4.4b has been spreading globally since 2022, causing mortality and morbidity in domestic and wild birds and mammals, including infection in humans, raising concerns about its pandemic potential. We aimed to generate a panel of anti-hemagglutinin (HA) human monoclonal antibodies (mAbs) against the H5 protein of clade 2.3.4.4b. H2L2 Harbour Mice, which express human immunoglobulin germline genes, were immunized with H5 and N1 recombinant proteins from A/mallard/New York/22-008760-007-original/2022 H5N1 virus, enabling the generation of human chimeric antibodies. Through hybridoma technology, sixteen full human mAbs were generated, most of which showed cross-reactivity against H5 proteins from different virus variants. The functionality of the sixteen mAbs was assessed in vitro using hemagglutination inhibition and microneutralization assays with viruses containing a clade 2.3.4.4b HA. Fourteen out of the sixteen mAbs neutralized the virus in vitro. The mAbs with the strongest hemagglutination inhibition activity also demonstrated greater neutralizing capacity and showed increased protective effects in vivo when administered prophylactically or therapeutically in a murine H5N1 challenge model. Using cryo-electron microscopy, we identified a cross-clonotype conserved motif that bound a hydrophobic groove on the head domain of H5 HA. Akin to mAbs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the coronavirus 2019 (COVID-19) pandemic, these mAbs could serve as important treatments in case of a widespread H5N1 epidemic or pandemic.
### Competing Interest Statement
The Icahn School of Medicine at Mount Sinai has filed patent applications regarding the described H5 mAbs which list GPA, JAD and FK as inventors. The Icahn School of Medicine at Mount Sinai has filed patent applications relating to SARS-CoV-2 serological assays, NDV-based SARS-CoV-2 vaccines influenza virus vaccines and influenza virus therapeutics which list FK as co-inventor and FK has received royalty payments from some of these patents. Mount Sinai has spun out a company, Kantaro, to market serological tests for SARS-CoV-2 and another company, Castlevax, to develop SARS-CoV-2 vaccines. FK is co-founder and scientific advisory board member of Castlevax. FK has consulted for Merck, GSK, Sanofi, Curevac, Seqirus and Pfizer and is currently consulting for 3rd Rock Ventures, Gritstone and Avimex. The Krammer laboratory is also collaborating with Dynavax on influenza vaccine development and with VIR on influenza virus therapeutics. ABW has received royalty payments for the licensure of a prefusion coronavirus spike stabilization technology for which he is a co-inventor. ABW is currently consulting for Third Rock Ventures and Merida Biosciences. Julianna Han and Andrew Ward are consultants for Third Rock Ventures.
What is H5N9? H5N9 is a rare subtype of the influenza A virus that can cause highly pathogenic avian influenza (HPAI), also known as bird flu. It's a reassortment strain that originated from the H5N1, H7N9, and H9N2 subtypes
U.S. authorities also identified the more common H5N1 strain on the same farm in Merced County, California.
Comparative Mutational Analysis and the Glycosylation Patterns of a Peruvian Isolated Avian Influenza a Virus H5N1: Exploring Possible Viral Spillover Events Within One Health Approach
(1) Background: The emergence of H5N1 Influenza A viruses clade 2.3.3.4b since 2020, have caused the mortality of thousands of birds/mammals worldwide, through evolu-tionary changes have been associated with acquired mutations and posttranslational modifications. (2) Methods: This study aimed to compare the mutational profile of H5N1 avian Influenza virus isolated from a Peruvian natural reserve, with recent data from other related international studies made in human and different species of domestic and wild birds and mammals. Briefly, the near complete protein sequences of Influenza virus coming from a Calidris alba were analyzed in a multisegmented level, altogether with 55 samples collected between 2022-2024 in different countries. Moreover, the glycosylation patterns were also predicted in silico. (3) Results: A total of 603 amino acid changes were found among H5N1 viruses analyzed, underscoring the detection of critical mutations HA:143T, HA:156A, HA:208K, NA: 71S, NP:52H, PA:336M, PA:36T, PA:85A/N, PB1-F2:66S, PB2:199S, PB2:292V, PB2:559T, as well as PA:86I, PA:432I, PA:558L, HA:492D, NA:70D, NS1-83P, PB1:515A, PA-X:57Q, PB1-F2:22E, NS1-21Q, NEP:67G, among others, considered of importance under One Health perspective. Similarly, changes in the N-linked glycosylation sites (NLGs) predicted in both HA and NA proteins were found, highlighting the loss/acquisition or changes in some NLGs sites such as 209NNTN, 100 NPTT, 302NSSM (HA) and 70NNTN, 68NISS, 50NGSV (NA). (4) Conclu-sions: This study provides our understanding about the evolution of current Influenza A viruses H5N1 HPAIV circulating globally. These findings outline the importance of sur-veillance updating mutational profiles and glycosylation patterns of these highly evolved virus.
Neuraminidase reassortment and oseltamivir resistance in clade 2.3.4.4b A(H5N1) viruses circulating among Canadian poultry, 2024 - PubMed
We report the detection of a clade 2.3.4.4b A(H5N1) reassortant virus with a neuraminidase surface protein derived from a North American lineage low-pathogenic avian influenza virus. This virus caused a widespread and ongoing outbreak across 45 poultry farms in British Columbia, Canada. Isolates fro …