Skip to main content

Posts

Showing posts from January 15, 2025

Clade 2.3.4.4b but not historical clade 1 #HA replicating #RNA #vaccine protects against #bovine #H5N1 challenge in #mice

Abstract The ongoing circulation of influenza A H5N1 in the United States has raised concerns of a pandemic caused by highly pathogenic avian influenza. Although the United States has stockpiled and is prepared to produce millions of vaccine doses to address an H5N1 pandemic, currently circulating H5N1 viruses contain multiple mutations within the immunodominant head domain of hemagglutinin (HA) compared to the antigens used in stockpiled vaccines . It is unclear if these stockpiled vaccines will need to be updated to match the contemporary H5N1 strains. Here we show that a replicating RNA vaccine expressing the HA of an H5N1 isolated from a US dairy cow confers complete protection against homologous lethal challenge in mice. A repRNA encoding the HA of a clade 1 H5 from 2004 (A/Vietnam/1203/2004) as utilized by some stockpiled vaccines, confers only partial protection . Our data highlight the utility of nucleic acid vaccines to be rapidly updated to match emergent viruses of concern w...

GGCX promotes #Eurasian #avian-like #H1N1 #swine #influenza virus #adaption to interspecies #receptor binding

Abstract The Eurasian avian-like (EA) H1N1 swine influenza virus (SIV) possesses the capacity to instigate the next influenza pandemic , owing to its heightened affinity for the human-type α-2,6 sialic acid (SA) receptor . Nevertheless, the molecular mechanisms underlying the switch in receptor binding preferences of EA H1N1 SIV remain elusive. In this study, we conduct a comprehensive genome-wide CRISPR/Cas9 knockout screen utilizing EA H1N1 SIV in porcine kidney cells. Knocking out the enzyme gamma glutamyl carboxylase (GGCX) reduces virus replication in vitro and in vivo by inhibiting the carboxylation modification of viral haemagglutinin (HA) and the adhesion of progeny viruses, ultimately impeding the replication of EA H1N1 SIV. Furthermore, GGCX is revealed to be the determinant of the D225E substitution of EA H1N1 SIV, and GGCX-medicated carboxylation modification of HA 225E contributes to the receptor binding adaption of EA H1N1 SIV to the α-2,6 SA receptor. Taken together, our...

#Outbreak of suspected #Marburg Virus Disease - United Republic of #Tanzania

Description of the situation Introduction On 13 January 2025, WHO informed its Member States and IHR State Parties of an outbreak of suspected Marburg Virus Disease (MVD) in the Kagera region of the United Republic of Tanzania using our secure web-based platform—the Event Information Site (EIS). Under the International Health Regulations, the EIS is used to issue rapid alerts to Member States of acute and rapidly developing public health risks and events with possible international implications. Summary of the situation On 10 January 2025, WHO received reliable reports from in-country sources regarding suspected cases of MVD in the Kagera region of the United Republic of Tanzania. Six people were reported to have been affected , five of whom had died . The cases presented with similar symptoms of headache, high fever, back pain, diarrhoea, haematemesis (vomiting with blood), malaise (body weakness) and, at a later stage of disease, external haemorrhage (bleeding from orifices). As of 1...