Elastase-Dependant Live Attenuated Swine Influenza Virus Vaccine in Pigs

Swine influenza (SI) is an acute, highly contagious, respiratory disease of swine caused by influenza A viruses. In addition, SI infections possess significant human public health concerns as they may serve as intermediate host for the generation of new pandemic viruses. Vaccination is still the primary method for the prevention and control of SI. Currently, commercially available vaccines against SI are a combination of inactivated swine influenza viruses (SIVs) with oil adjuvant. Their application induces mainly humoral immune response, which may not be protective against virus variation in the field. In contrast, application of live attenuated influenza vaccines (LAIV) mimics natural infection and induces strong, cell-mediated and humoral immunity. Furthermore, LAIV induces cross-protective immunity against different subtypes of influenza A viruses and are currently unavailable for SI. Using reverse genetics technology we generated mutant SIVs with the modified cleavage site within hemagglutinin (HA) segment. These viruses are fully dependent on the presence of human neutrophil elastase for their growth in tissue culture and are completely attenuated when administered to pigs. Furthermore, application of these live attenuated, elastase-dependent swine influenza viruses as a live vaccines resulted in the significant protective humoral (systemic and mucosal), cell-mediated and cross-reactive immunity in pigs. The purpose of this review is to provide recent advances in SIV live vaccine development by modifying the hemagglutinin cleavage site. Here, we review the design and generation of elastasedependent mutant SIV by reverse genetics; evaluation of its genetic stability and pathogenicity in pigs; evaluation of its immunogenicity and protection efficacy after intratracheal and intranasal application to diverse SIV challenges including 2009 pandemic H1N1 virus.