Vaccine efficacy of live-attenuated, whole inactivated and alphavirus vectored vaccines against antigenically distinct H3N2 swine influenza A viruses

Influenza A virus (IAV) is an important pathogen in swine, and the main intervention strategy is vaccination to induce neutralizing antibodies against the hemagglutinin (HA). Three major antigenic clusters, cyan, red, and green, were identified among H3N2 viruses circulating in pigs in the U.S. and were associated with amino acid changes in 6 key sites in the HA protein. In this study, we compared the efficacy of different vaccine platforms including adjuvanted whole inactivated virus (WIV), live-attenuated influenza virus (LAIV), and an alphavirus vectored vaccine against challenge strains that were antigenically distinct.

Three animal experiments were carried out: experiment 1 used cyan antigenic virus WIV and LAIV against a heterologous red antigenic virus; experiment 2 used alphavirus vectored monovalent and bivalent vaccines expressing the HA of green and/or red antigenic viruses against homologous and heterologous challenge; and experiment 3 used green antigenic virus WIV and LAIV against homologous green and heterologous red challenge.

Pigs were challenged with each assigned virus, and nasal swabs were collected at 0, 1, 3, and 5 days post-infection (DPI) from pigs. At 5 DPI, lung and trachea lesions were evaluated and bronchoalveolar lavage fluid collected. Virus isolation, virus titer, hemagglutination inhibition (HI) assays, lung lesion scoring and mucosal antibody quantitation were performed.

In these studies, reduced cross-reactivity in HI assays was observed when tested against heterologous antigens, validating the significance of the cyan, red and green antigenic clusters. The levels of cross-protection against antigenically distinct challenge viruses varied across the vaccine platforms with LAIV as the most effective, the alphavirus vectored vaccine as intermediate, and the WIV providing the least amount of cross-protection. Enhanced lung lesions were observed when pigs were vaccinated with the green WIV and challenged with the red antigenic virus.

The main strategy used to prevent or reduce morbidity of IAV in swine is to employ commercially available and farm-specific autogenous vaccines. These studies will help to define the importance of the 6 antigenic sites to vaccine efficacy and indicate the number of H3N2 viruses required to be included in multivalent vaccines to cover the breadth of antigenic variants of H3 swine IAV co-circulating in the U.S. Amino acids at these 6 antigenic positions in the HA were associated with antigenic cross-reactivity of swine H3 IAV in the U.S. and attention to these sites could facilitate the rapid detection of antigenically drifted viruses.

Disclosure of Interest: None Declared.