| Budget Amount *help |
¥3,920,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥420,000)
Fiscal Year 2007: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2006: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Research Abstract |
In the present study, we found that superinfection with non-lethal doses of influenza virus and several kinds of oral streptococci(Streptococcus mutans, S. sanguis, S. salivarius, S. equi) let more than 60% of mice to death. The result suggests that infection with oral streptocci which do not have severe virulent factor can be lethal in addition to prior non-lethal influenza infection. However, it still remains which virulence foctor is a key mediator for induction of lethal influenza-oral streptococcal superinfection.
Immunization of mice with influenza HA vaccine did not protect from the lethal superinfection. We found that influenza HA immunization did not protect from influenza infection with mouse alveolar epithelial cells completely, thus, a few of influenza infected cells were co-infected with oral bacteria. The result indicate that the available vaccine adjuvant that enhances protective immnue responses to delete influenza virus completely is needed for protection from the super
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infection. Here we tested whether amphiphilic poly(γ-glutamic acid)-graft-L-phenylalanine copolymers(γ-PGA-NPs), which are derived from a bacterial capsular exopolymer produced by certain Bacillus natto strains, were an effective adjuvant for systemic influenza HA vaccination. Subcutaneous immunization with a mixture of HA vaccine and γ-PGA-NPs induced higher mononuclear cell proliferation and the production of γ-interferon(IFN-γ), interleukin(IL)-4, and IL-6 upon HA restimulation, and enhanced not only anti-HA neutralizing antibody production but also the influenza virus-specific cell-mediated immune response, including CTL activity, compared with immunization with HA alone or a mixture of HA and aluminum adjuvant. HA vaccine with γ-PGA-NPs protected mice against challenges with lethal doses of homologous influenza virus. The results indicate that adding γ-PGA-NPs to the HA vaccine promotes effective protection, and identify γ-PGA-NPs as a new, effective, and potent candidate adjuvant for a subcutaneous influenza virus vaccine. Less
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