A recombinant chimeric influenza virus vaccine expressing the consensus H3 hemagglutinin elicits broad hemagglutination inhibition antibodies against divergent swine H3N2 influenza viruses

The global distribution and ongoing evolution of type A swine influenza virus (IAV-S) continue to pose significant challenges against developing broadly protective vaccines to control swine influenza. This study focuses on the hemagglutinin (HA) consensus-based approach towards developing a more broadly protective swine influenza vaccine against various H3 strains circulating in domestic pig populations. By computationally analyzing >1000 swine H3 full-length HA sequences, we generated a consensus H3 and expressed it in the context of influenza A WSN/33 reverse genetics system. The derived recombinant chimeric swine influenza virus with the consensus H3 was inactivated and further evaluated as a potential universal vaccine in pigs. The consensus H3 vaccine elicited broadly active hemagglutination inhibition (HI) antibodies against divergent swine H3N2 influenza viruses including human H3N2 variant of concern, and strains belong to genetic clusters IV, IV-A, IV-B, IV-C, IV-D and IV-F. Importantly, vaccinated pigs were completely protected against challenge with a clinical swine H3N2 isolate in that neither viral shedding nor replication in lungs of vaccinated pigs were observed. These findings warrant further study of the consensus H3 vaccine platform for broad protection against diverse swine influenza viruses.