Cross-protection against influenza virus infection in mice vaccinated by combined nasal/subcutaneous administration

The effects of a combination of intranasal (i.n.) and subcutaneous (s.c.) administration of inactivated influenza vaccine for priming and boosting on the cross-protection against antigenically drifted virus challenge were examined in Balb/c mice. Mice were primed through the i.n. or s.c. route with a CTB*-A/Kumamoto/37/79 (H1N1) combined vaccine (CTB*: cholera toxin B subunit supplemented with 0.2% of the holotoxin) and boosted through the i.n. or s.c. route with another drift virus vaccine, A/Bangkok/10/83 (H1N1), 4 weeks later. Two weeks after boosting, the mice were challenged with a third drift virus, A/Yamagata/120/86 (H1N1). The combination of i.n. priming and i.n. boosting afforded the highest cross-protection, while combinations of s.c. priming and i.n. or s.c. boosting afforded little cross-protection. In parallel with the protective activity, anti-A/Yamagata haemagglutinin-reactive IgA and IgG antibodies were detected in nasal and bronchoalveolar wash specimens. These results suggest that cross-protection against a variant virus challenge is most favourably provided by i.n. priming with the CTB* combined vaccine and i.n. boosting with the vaccine, which optimally induces cross-protective IgA and IgG antibodies.