#ah1n1 — Public Fediverse posts
Live and recent posts from across the Fediverse tagged #ah1n1, aggregated by home.social.
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Structural Convergence and Water-Mediated Substrate Mimicry Enable Broad #Neuraminidase #Inhibition by #Human #Antibodies
Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2024.11.27.625426v1?rss=1
Abstract
Influenza has been responsible for multiple global pandemics and seasonal epidemics and claimed millions of lives. The imminent threat of a panzootic outbreak of avian influenza H5N1 virus underscores the urgent need for pandemic preparedness and effective countermeasures, including monoclonal antibodies (mAbs). Here, we characterize human mAbs that target the highly conserved catalytic site of viral neuraminidase (NA), termed NCS mAbs, and the molecular basis of their broad specificity. Cross-reactive NA-specific B cells were isolated by using stabilized NA probes of non-circulating subtypes. We found that NCS mAbs recognized multiple NAs of influenza A as well as influenza B NAs and conferred prophylactic protections in mice against H1N1, H5N1, and influenza B viruses. Cryo-electron microscopy structures of two NCS mAbs revealed that they rely on structural mimicry of sialic acid, the substrate of NA, by coordinating not only amino acid side chains but also water molecules, enabling inhibition of NA activity across multiple influenza A and B viruses, including avian influenza H5N1 clade 2.3.4.4b viruses. Our results provide a molecular basis for the broad reactivity and inhibitory activity of NCS mAbs targeting the catalytic site of NA through substrate mimicry.____
#aH1n1 #aH5n1 #abstract #avianInfluenza #AVIANINFLUENZA #birdFlu #h5n1 #health #influenzaB #monoclonalAntibodies #news #research #SEASONALINFLUENZA
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Boosting #neuraminidase #immunity in the presence of #hemagglutinin with the next generation of #influenza #vaccines
Source: npj Vaccines, https://www.nature.com/articles/s41541-024-01011-x
Abstract
Neuraminidase (NA), the second most abundant surface glycoprotein on the influenza virus, plays a key role in viral replication and propagation. Despite growing evidence showing that NA-specific antibodies correlate with resistance to disease in humans, current licensed vaccines focus almost entirely on the hemagglutinin (HA) antigen. Here, we demonstrate that recombinant NA (rNA) protein is highly immunogenic in both naïve mice and ferrets, as well as in pre-immune ferrets, irrespective of the level of match with preexisting immunity. Ferrets vaccinated with rNA developed mild influenza disease symptoms upon challenge with human H3N2 influenza virus, and anti-NA antibody responses appeared correlated with reduction in disease severity. The addition of rNA to a quadrivalent HA-based vaccine induced robust NA-specific humoral immunity in ferrets, while retaining the ability to induce HA-specific immunity. These results demonstrate that the addition of rNA is a viable option to increase immunogenicity and potentially efficacy versus currently licensed influenza vaccines by means of boosting NA immunity.____
#aH1n1 #aH3n2 #abstract #animalModels #health #influenzaA #mrna #news #research #vaccine #vaccines
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Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2024.10.23.619695v1
Abstract
The most recent outbreak of highly pathogenic avian H5 influenza (HPAI) virus in cattle is now widespread across the U.S. with spillover events happening to other mammals, including humans. Several human cases have been reported with clinical signs ranging from conjunctivitis to respiratory illness. However, most of those infected report mild to moderate symptoms, while previously reported HPAI H5Nx infections in humans have had mortality rates upwards of 50%. We recently reported that mice with pre-existing immunity to A/Puerto Rico/08/1934 H1N1 virus were protected from lethal challenge from highly pathogenic clade 2.3.4.4b H5N1 influenza virus. Here, we demonstrate that mice infected with the 2009 pandemic H1N1 virus strain A/California/04/2009 (Cal09) or vaccinated with a live-attenuated influenza vaccine (LAIV) were moderately-to-highly protected against a lethal A/bovine/Ohio/2024 H5N1 virus challenge. We also observed that ferrets with mixed pre-existing immunity, either from LAIV vaccination and/or from Cal09 infection, showed protection against a HPAI H5N1 clade 2.3.4.4b virus isolated from a cat. Notably, this protection occurred independently of any detectable hemagglutination inhibition titers (HAIs) against the H5N1 virus. To explore factors that may contribute to protection, we conducted detailed T cell epitope mapping using previously published sequences from H1N1 strains. This analysis revealed a high conservation of amino acid sequences within the internal proteins of our bovine HPAI H5N1 virus strain. These data highlight the necessity to explore additional factors that contribute to protection against HPAI H5N1 viruses, such as memory T cell responses, in addition to HA-inhibition or neutralizing antibodies.____
#aH1n1 #aH5n1 #abstract #animalModels #avianInfluenza #AVIANINFLUENZA #birdFlu #ferrets #h1n1pdm09 #h5n1 #health #immuneSystem #news #research