ETIDIOH - NEW

  Highlights •  IN-delivered ChAd-Texas vaccine elicits mucosal antibody and T cell responses •  IN-delivered ChAd-Texas vaccine protects against H5N1 in mice and hamsters •  IN delivery of ChAd-Texas vaccine confers greater protection than IM delivery •  ChAd-Texas induces H5N1 immunity in the setting of prior influenza immunity Summary The emergence of highly pathogenic avian H5N1 influenza viruses in dairy cows and humans has increased the potential for another pandemic . To address this risk, we developed chimpanzee adenoviral (ChAd)-vectored H5 hemagglutinin-targeted vaccines and tested their immunogenicity and efficacy in rodents . Immunization with ChAd-Texas (clade 2.3.4.4b) vaccine in mice elicits neutralizing antibody responses and confers protection against viral infection and mortality upon challenge with a human H5N1 isolate (A/Michigan/90/2024, clade 2.3.4.4b). Intranasal delivery of the ChAd-Texas vaccine elicits mucosal antibody and T cell respon...

Abstract Key to the success of influenza A virus as a pathogen are its numerous tactics of immune evasion. To suppress anti-viral cellular and organismal responses , influenza A virus encodes several immunomodulatory proteins , including the endoribonuclease PA-X . PA-X decreases inflammation and immune responses in in vivo infections by limiting host gene expression . PA-X is conserved in 99% of all influenza A viral strains , pointing to its importance as a crucial immunomodulator . However, it is not yet known how PA-X activity alters the antiviral response in the human airway or how it benefits the virus. To define how influenza A virus uses this protein to evade immune responses , we characterized the impacts of PA-X on the host response to infection in the infected and bystander cells of the airway epithelium using a 3D ex vivo model. We discovered that PA-X exerts a dual action on immune responses , dampening aspects of both the innate and adaptive immune systems . Consistent wi...