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Showing posts from August 8, 2025

A versatile #H5N1-VSV #platform for safe #influenza virus #research applications

  ABSTRACT The H5N1 strain of influenza A virus (IAV) continues to cause severe infections in a range of avian and mammalian species , including sporadic but concerning cases in humans. There is growing concern that circulating H5N1 strains could lead to widespread human outbreaks . Research with highly pathogenic H5N1 viruses is restricted to Biosafety Level 3 (BSL-3) laboratories. Vesicular stomatitis virus (VSV)-based vaccine vectors expressing heterologous viral proteins from Ebola, SARS-CoV-2, Lassa virus, etc., have previously been shown to be safe and effective in animal models and human clinical trials . Here, we report the development of a recombinant VSV expressing the hemagglutinin (HA) and neuraminidase (NA) genes of H5N1 IAV (H5N1-VSV), which serves as a versatile platform to study various aspects of H5N1 IAV biology. H5N1-VSV replicated robustly to titers comparable to those of the full H5N1 virus in multiple cell lines. In mice , H5N1-VSV vaccination was safe, elicit...

#Inflammatory, transcriptomic, and #cell fate responses underlying the #mammalian #transmission of avian #influenza viruses

  ABSTRACT Airborne transmissibility of avian influenza viruses (AIVs) in humans is considered an essential component of their pandemic risk . Although several viral factors regulating airborne transmission (AT) have been delineated, it is not known what, if any, responses at the respiratory epithelia are determinants of AIV AT. Using responses in the ferret nasal epithelium to a panel of H1N1 AIVs, we describe host responses that segregate with AT phenotypes . AIV infection upregulated interferon alpha and gamma responses and IL-6 JAK-STAT signaling and downregulated oxidative phosphorylation . Single-cell transcriptomics revealed that cellular genotoxic stress and NF-kB, interferon, and cell fate pathways differentiated host responses to AIVs with different transmissibilities. These responses culminated in greater AIV antigen-containing exudate and debris in the respiratory spaces of the nasal epithelium of ferrets inoculated with AT AIVs. More abundant CMPK2, SP100, and CXCL10 t...

#USA, #Wastewater Data for Avian #Influenza #H5 (#CDC, August 8 '25)

  {Summary} Time Period: July 27, 2025 - August 02, 2025 -- H5 Detection :  4 sites ( 0.9% ) -- No Detection :  430 sites (99.1%) -- No samples in last week :  24 sites (...) Source: US Centers for Disease Control and Prevention,  https://www.cdc.gov/nwss/rv/wwd-h5.html ____

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

  Two Poultry Farms in the Odisha State. Source: WOAH,  https://wahis.woah.org/#/in-review/6694 ____

Post-exposure #prophylaxis regimen of #rabies monoclonal #antibody and #vaccine in category 3 potential exposure patients ...

  Summary Background Rabies is almost invariably fatal . A rabies monoclonal antibody (RmAb) was approved in India in 2016 for passive prophylaxis. This post-marketing study aimed to evaluate the long-term safety, immunogenicity, and efficacy of a post-exposure prophylaxis (PEP) regimen containing RmAb. Methods This phase 4, open-label, randomised, active-controlled study was conducted at 15 tertiary care hospitals in India . Patients aged 2 years or older with WHO category 3 rabies exposure by a suspected rabid animal were eligible if the exposure occurred less than 72 h before enrolment, or less than 24 h before enrolment for exposures to the face, neck, hand, or fingers. Participants were randomly assigned (3:1) to receive either RmAb (Rabishield; Serum Institute of India, Pune, India) plus a purified Vero cell rabies vaccine (PVRV; Rabivax-S) or equine rabies immunoglobulin (ERIG; Equirab) plus PVRV as PEP. In each treatment group, patients were further randomly assigned (1:1) ...

#MERS-related #coronavirus circulating in #pangolins exhibits strong fusogenicity in #human #cells and high sensitivity to fusion inhibitors

Highlights •  MjHKU4r-CoV-1 with high fusogenicity induces inflammatory responses in human cells •  6-HB structure determination unveils MjHKU4r-S-mediated membrane fusion mechanism •  MjHKU4r-CoV-1 HR2 peptides exhibit potent activity by targeting viral HR1 domain •  Stapled peptide MjHKU4r-HR2P10 shows potent and broad-spectrum anti-CoV activity Summary Unlike preceding MERS-related coronaviruses, the recently identified MjHKU4r-CoV-1 strain can directly infect human cells . Nonetheless, its potential pathogenic attributes and underlying molecular mechanisms remain unclear. We find that MjHKU4r-CoV-1 induces significant inflammation , including interleukin (IL)-6 and tumor necrosis factor alpha (TNF-α), and exhibits pronounced fusogenicity mediated by its spike (S) protein, leading to extensive syncytium formation . This suggests the possibility that MjHKU4r-CoV-1 possesses strong pathogenic potential in humans . Further, we successfully reveal the molecular mechan...

Highly conserved #Betacoronavirus #sequences are broadly recognized by #human T cells

Highlights •  Conserved T cell epitope regions elicit strong CD4+ and CD8+ T cell responses in SARS2-exposed •  CTERs enhance cross-reactivity across multiple Betacoronaviruses •  Targeting non-spike proteins expands immune breadth and HLA coverage •  Removing low population coverage regions preserves cross-reactivity Summary The COVID-19 pandemic highlighted the critical need for vaccine strategies capable of addressing emerging viral threats . Betacoronaviruses, including severe acute respiratory syndrome coronavirus ( SARS-CoV ), Middle East respiratory syndrome ( MERS ), and SARS-CoV-2 , present significant pandemic risks due to their zoonotic potential and genetic diversity . T cell-mediated immunity has demonstrated durable responses and strong cross-reactivity, offering a promising avenue for achieving broad immunity within a viral family. In this study, we combined comprehensive epitope mapping with sequence conservation analyses to identify conserved T cell ...