Protective efficacy of intranasally administered bivalent live influenza vaccine and immunological mechanisms underlying the protection.

Previously we reported the generation of a new potential live attenuated influenza vaccine (LAIV) named SIV/606 that expresses H1 and H3 HAs. We also demonstrated intratracheal vaccination of SIV/606 conferred protection against infections with both H1 and H3 swine influenza virus subtypes in pigs. Here we vaccinated pigs with SIV/606 intranasally, which is a more suitable route for LAIV, and evaluated vaccine efficacy. Intranasal vaccination of SIV/606 induced serum IgG antibody responses against both H1N1 and H3N2 SIVs and high titer of virus neutralizing antibodies against H1N1 SIV but not against H3N2 SIV. When we challenged the pigs with H1N1 and H3N2 SIVs, we observed marked reduction of lung lesions and viral titer in lung tissue in vaccinated pigs. Our analyses also showed that vaccinated pigs had more IFN-γ secreting cells in trachea-bronchial lymph nodes. Our studies demonstrated that intranasal vaccination of SIV/606 is efficacious for H1N1 and H3N2 SIVs infections. Moreover, our results may help explaining the protection from H3N2 SIV infection despite the low viral neutralizing antibody titer.