Assessment of Immune Responses to a Trivalent Pichinde Virus-Vectored Vaccine Expressing Hemagglutinin Genes from Three Co-Circulating Influenza A Virus Subtypes in Pigs

Pichinde virus (PICV) can infect several animal species and has been developed as a safe and effective vaccine vector. Our previous study showed that pigs vaccinated with a recombinant PICV-vectored vaccine expressing the hemagglutinin (HA) gene of an H3N2 influenza A virus of swine (IAV-S) developed virus-neutralizing antibodies and were protected against infection by the homologous H3N2 strain. The objective of the current study was to evaluate the immunogenicity and protective efficacy of a trivalent PICV-vectored vaccine expressing HA antigens from the three co-circulating IAV-S subtypes: H1N1, H1N2, and H3N2. Pigs immunized with the trivalent PICV vaccine developed virus-neutralizing (VN) and hemagglutination inhibition (HI) antibodies against all three matching IAV-S. Following challenge infection with the H1N1 strain, five of the six pigs vaccinated with the trivalent vaccine had no evidence of IAV-S RNA genomes in nasal swabs and bronchoalveolar lavage fluid, while all non-vaccinated control pigs showed high number of copies of IAV-S genomic RNA in these two types of samples. Overall, our results demonstrate that the trivalent PICV-vectored vaccine elicits antibody responses against the three targeted IAV-S strains and provides protection against homologous virus challenges in pigs. Therefore, PICV exhibits the potential to be explored as a viral vector for delivering multiple vaccine antigens in swine.