ETIDIOH - NEW

Abstract The H1N1 swine influenza viruses CQ91 and CQ445, isolated from pigs in China, exhibited distinct virulence in mice despite sharing similar genomic constellations. CQ91 demonstrated higher pathogenicity (MLD50: 5.4 log10 EID50) and replication efficiency in mice compared to CQ445 (MLD50: 6.6 log10 EID50). Through reverse genetics, we found that the attenuation of CQ445 was due to a single substitution of glutamic acid (E) with lysine (K) at position 343 in the PB2 protein . Introducing the CQ445-PB2 (343K) into CQ91 significantly reduced viral replication and pathogenicity in mice, while replacing CQ445-PB2 with CQ91-PB2 (343E) restored virulence. In vitro studies showed that the K343E mutation impaired viral replication in MDCK and A549 cells and reduced polymerase activity in minigenome assays. Mechanistically, the amino acid at position 343 in the PB2 affects the transcription stage of the viral replication process . Structural modeling indicated that the charge reversal cau...

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Abstract With the recent rise in cases of highly pathogenic avian influenza (HPAI) A(H5N1) clade 2.3.4.4b infection in humans and animals , there is an associated increase in the risk of human-to-human transmission . In this study, we characterize a recombinant A(H5N1) A/American Wigeon/South Carolina/22/000345-001/2021 (A/AW/SC/2021) clade 2.3.4.4b vaccine . Purified recombinant A/AW/SC/2021 HA trimers formulated with Matrix-M® adjuvant, saponin-cholesterol-phospholipid combination arranged in cage-like particles, are found to non-covalently anchor to the vertices of the Matrix-M and form A(H5N1) HA–Matrix-M nanoparticles (H5-MNPs). In naïve female mice , two intranasal (IN) or intramuscular (IM) doses of A/AW/SC/2021 H5-MNP vaccine induces robust antibody- and cell-mediated immune responses , including neutralizing antibodies against A(H5N1). In non-human primates (NHPs) primed with seasonal influenza vaccine , a single IM or IN dose of the A/AW/SC/2021 H5-MNP vaccine induces geometr...