A bivalent live attenuated influenza virus vaccine protects against H1N2 and H3N2 viral infection in swine

Vet Microbiol. 2021 Feb;253:108968. doi: 10.1016/j.vetmic.2020.108968. Epub 2020 Dec 28.

Abstract

Swine Influenza A virus (swIAV) poses a substantial burden to the swine industry due to its highly contagious nature, acute viral disease, and ability to cause up to 100 % morbidity. Currently, North American swine are predominately infected with three subtypes of swIAV: H1N1, H1N2, and H3N2. The ability of influenza viruses to cross both directions between humans and swine means that both human and swine-origin viruses as well as new reassortant viruses can pose a substantial public health or pandemic threat. Since the primary method of protection and control against influenza is through vaccination, more effective, new vaccine platforms need to be developed. This study uses two Canadian swIAV isolates, A/Swine/Alberta/SD0191/2016 (H1N2) [SD191] and A/Swine/Saskatchewan/SD0069/2015 (H3N2) [SD69] to design a bivalent live attenuated influenza virus vaccine (LAIV) through reverse genetics. The hemagglutinin (HA) cleavage site from both SD191-WT and SD69-WT were engineered from a trypsin-sensitive to an elastase-sensitive motif, to generate SD191-R342V and SD69-K345V, respectively. The elastase dependent SD191-R342V virus possesses a mutation from arginine to valine at amino acid (aa) 342 on HA, whereas the elastase dependent SD69-K345V virus possesses a mutation from lysine to valine at aa 345 on HA. Both elastase dependent swIAVs are completely dependent on elastase, display comparable growth properties to the wild type (WT) viruses, are genetically stable in vitro, and entirely non-virulent in pigs. Moreover, when these elastase dependent swIAVs were administered together in pigs, they were found to stimulate antibody responses and IFN-γ secreting cells, as well as prevent viral replication and lung pathology associated with WT H1N2 and H3N2 swIAV challenge. Therefore, this bivalent LAIV demonstrates the strong candidacy to protect swine against the predominant influenza subtypes in North America.

Keywords: Bivalent live attenuated virus vaccine; Elastase dependent influenza viruses; Swine Influenza A virus.