Efficacy of intranasal administration of a truncated NS1 modified live influenza virus vaccine in swine

In the U.S., despite available swine influenza virus (SIV) vaccines, multiple influenza subtypes as well as antigenic and genetic variants within subtypes continue to circulate in the swine population. One of the challenges to control and eliminate SIV is that the currently used inactivated influenza virus vaccines do not provide adequate cross-protection against multiple antigenic variants of SIV in the field. We previously generated a recombinant H3N2 swine influenza virus (SIV) based on the influenza A/SW/TX/4199-2/98 virus (TX98) containing an NS1 gene expressing a truncated NS1 protein of 126 amino acids, TX98-NS1Δ126 virus. This recombinant strain was demonstrated to be highly attenuated in swine and showed potential for use as a modified live-virus vaccine (MLV) after intratracheal application in pigs. However, this route of inoculation is not practical for vaccination in the field. In the present study, we first compared intramuscular and intranasal routes of application of the MLV, and found that the intranasal route was superior in priming the local (mucosal) immune response. Pigs were then vaccinated via the intranasal route and challenged with wild type homologous TX98 H3N2 virus, with a genetic and antigenic variant H3N2 SIV (influenza A/SW/CO/23619/99 virus, CO99) and a heterosubtypic H1N1 SIV (influenza A/SW/IA/00239/2004 virus, IA04). The intranasally vaccinated pigs were completely protected against homologous challenge. In addition, MLV vaccination provided nearly complete protection against the antigenic H3N2 variant CO99 virus. When challenged with the H1N1 IA04 virus, MLV vaccinated animals displayed reduced fever and virus titers despite minimal reduction in lung lesions. In vaccinated pigs, there was no serologic cross-reactivity by HI assays with the heterologous or heterosubtypic viruses. However, there appeared to be substantial cross-reactivity in antibodies at the mucosal level with the CO99 virus in MLV vaccinated pigs.