Vaccination of pigs with a codon-pair bias de-optimized live attenuated influenza vaccine protects from homologous challenge

Influenza A virus (IAV) in swine constitutes a major economic burden for producers as well as a potential threat to public health. Whole inactivated virus vaccines (WIV) are the predominant countermeasure employed to control IAV in swine herds in the United States despite the superior protection, and diminished adverse effects, induced by live attenuated influenza vaccines (LAIV). A major hurdle for the development of LAIV exists in achieving the proper level of attenuation while maintaining immunogenicity. Using Synthetic Attenuated Virus Engineering (SAVE) to introduce codon-pair bias de-optimization (CPBD) into the hemagglutinin (HA) and neuraminidase (NA) gene segments of pandemic H1N1 IAV, a novel LAIV was produced and evaluated for attenuation, immunogenicity, and efficacy in pigs. The CPBD LAIV induced inappreciable pathology following intranasal administration yet induced robust serum and mucosal antibody titers. CPBD LAIV vaccinated pigs challenged with wild-type virus showed protection from disease and virus detection, highlighted by the absence of detectable virus titers in the nasal passages and lungs. These results demonstrate the efficacy of a LAIV designed by SAVE codon de-optimization in pigs, providing support for the continued development of CPBD LAIV for use in swine.