|Budget Amount *help
¥2,100,000 (Direct Cost : ¥2,100,000)
Fiscal Year 1992 : ¥700,000 (Direct Cost : ¥700,000)
Fiscal Year 1991 : ¥1,400,000 (Direct Cost : ¥1,400,000)
In our previous studies, We demonstrated that intranasal inoculation of influenza inactivated vaccine together with cholera toxin B subunit(CTB)into mice can provide cross-protection against variant virus infection in parallel with the induction of cross-reacting IgA antibodies (Ab) in the respiratory tract. The inactivated vaccine contained seven protein components of influenza virus. Among them, surface glycoprotein, hemagglutinin(HA), which varies slightly within the same subtype and largely within the same type, is known to be a major protein involved in the induction of protective antibodies. In addition, core protein, nucleoprotein(NP), which is cross-reactive in the same type, is known to be another major component involved in the recovery from influenza. The present study was designed to elucidate the role of HA and NP in the defense mechanism against influenza in the mice immunized intranasally together with CTB. This would lead to the development of the effective nasal influenza component vaccine. The results show that intranasal inoculation of PR8 HA molecules together with CTB into mice conferred protection against not only homologous virus infection but also heterologous virus infection. Moreover, the respiratory tract anti-HA IgA Ab from mice immunized with CTB-combined HA molecules mediated directly the cross-protection when transferred passively into the respiratory tract. Thus,the HA is one of the essential vaccine components in the blockade of infection in the nasally-vaccinated mice. On the other hand, intranasal inoculation of PR8 NP molecules together with CTB induced memory cells involved in the accelerated induction of CTL responses. Moreover, the accelerated elimination of virus-infected cells by CTL in the respiratory tract resulted in the facilitation of the recovery from influenza. Consequently, the NP seems to be also a useful vaccine component under the absence of local Ab.