A chimeric influenza hemagglutinin delivered by parainfluenza virus 5 vector induces broadly protective immunity against genetically divergent influenza a H1 viruses in swine

Abstract

Highlights An HA-based vaccine candidate, created by DNA shuffling (HA-113), can be immunogenic when the recombinant antigen is expressed by PIV5 (PIV5-113). Immunity induced by the PIV5-113 vaccine can protect mice against infection with 4 of 5 parental HAs used to create the vaccine. Immunity induced by PIV5-113 can protect pigs against infection with an influenza virus isolate that is known to be infectious in pigs.

Combined intranasal and intramuscular parainfluenza 5-, simian adenovirus ChAdOx1- and poxvirus MVA-vectored vaccines induce synergistically HIV-1-specific T cells in the mucosa

“…Our results expand previously published increases in the levels of humoral and cellular responses against various pathogens by PIV5-based candidate vaccines in mice, hamsters, guinea pigs, ferrets, dogs, monkeys and most recently in humans ( 25 , 27 , 52 – 59 ). For the influenza virus, these immune responses protected mice and pigs against a virus challenge ( 60 ). Thus, through parental PIV5 safety, broad cell tropism, cross-species applicability, needle-free delivery, evasion of pre-existing anti-PIV5 immunity, and induction of CD8 + T cells, and mucosal and systemic antibodies, the PIV5 vector is a strong candidate for a versatile vaccine platform.…”

Viral PB1-F2 and host IFN-γ guide ILC2 and T cell activity during influenza virus infection

“…Viruses containing the PB1 gene from either PR8 or CA04 viruses were created as 1:7 reassortants using the well-established, eight-plasmid reverse genetic system, as described previously ( 59 – 61 ). Plasmids for PR8 and CA04 viruses were kindly provided by Richard J. Webby, St. Jude Children’s Research Hospital, Memphis, TN.…”

Parainfluenza virus 5 is a next‐generation vaccine vector for human infectious pathogens

“…Notably, the candidate vaccine could be used to induce broad immunity against genetically diversified influenza viruses circulating in both pigs and humans. 91 However, B cells are mostly restricted to recognizing surface antigens (e.g., viral spike proteins). Once inside cells, intracellular pathogens are not readily accessible to antibodies.…”

“…One study selected four parental influenza A H1N1 strains (A/New Jersey/8/76, A/Iowa/1/06, A/Ohio/1/07, and A/Tennessee/1‐560/09) to represent distinct phylogenetic clades and evaluated the immunogenicity of PIV5‐vectored vaccines expressing chimeric HA antigen (PIV5‐113) in a murine challenge model, before further assessment of protective immunity in a nursery pig model. The resulting data showed that the levels of vaccine‐induced HA‐reactive antibodies against ME08 (non‐parental H1N1 influenza A virus strain used to assess cross‐reactivity) were significantly higher in animals immunized via a prime‐boost regimen of PIV5‐vectored vaccine 91 …”

“…In a recent study, a chimeric influenza hemagglutinin delivered by a PIV5 vector increased the level of antibodies against the parental influenza virus. Notably, the candidate vaccine could be used to induce broad immunity against genetically diversified influenza viruses circulating in both pigs and humans 91 …”