Development of adjuvant-combined nasal influenza vaccine

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Natural influenza virus has been shown to be superior to the inactivated vaccine for inducing cross-protection against variants within a subtype of A type virus. The cross-protection induced by natural infection seems to be largely due to the induction of cross-reacting IgA antibodies in the respiratory tract. These facts suggest that the development of immunization procedure to stimulate mucosal IgA antibody production would improve the protective efficacy of the current inactivated vaccine. In this regard, intranasal immunization of inactivated vaccine has been advocated as means of inducing secretory IgA and systemic IgG antibodies against influenza. However, the intranasal immunization of inactivated vaccine alone cannot easily generate the secretory IgA antibodies. Under these circumstances, we attempted to inoculate intranasally the current inactivated vaccine together with a potent adjuvant, cholera toxin B subunit (CTB) containing 0.1% of CT,in mice. The results demonstrated that the nasal administration of the adjuvant-combined vaccine into mice can mimic the efficacy of live virus in inducing cross-protection against variant virus challenge. Moreover, we examined the effect of the intranasal immunization of the adjuvant-combined vaccine on IgA and HI antibody responses in humans. The results demonstrated that the adjuvant-combined vaccine can elicit significantly not only secretory IgA antibody but also serum HI antibody, as compared with vaccine alone, in humans.