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Inactivated Influenza Vaccine That Provides Rapid, Innate-Immune- System-Mediated Protection and Subsequent Long-Term Adaptive Immunity


Chua e al. mBio.pdf1.48 MBPDF見る/開く

タイトル: Inactivated Influenza Vaccine That Provides Rapid, Innate-Immune- System-Mediated Protection and Subsequent Long-Term Adaptive Immunity
著者: Chua, Brendon Y. 著作を一覧する
Wong, Chinn Yi 著作を一覧する
Mifsud, Edin J. 著作を一覧する
Edenborough, Kathryn M. 著作を一覧する
Sekiya, Toshiki 著作を一覧する
Tan, Amabel C. L. 著作を一覧する
Mercuri, Francesca 著作を一覧する
Rockman, Steve 著作を一覧する
Chen, Weisan 著作を一覧する
Turner, Stephen J. 著作を一覧する
Doherty, Peter C. 著作を一覧する
Kelso, Anne 著作を一覧する
Brown, Lorena E. 著作を一覧する
Jackson, David C. 著作を一覧する
発行日: 2015年10月27日
出版者: American Society for Microbiology
誌名: mBio
巻: 6
号: 6
開始ページ: e01024-15
抄録: The continual threat to global health posed by influenza has led to increased efforts to improve the effectiveness of influenza vaccines for use in epidemics and pandemics. We show in this study that formulation of a low dose of inactivated detergent-split influenza vaccine with a Toll-like receptor 2 (TLR2) agonist-based lipopeptide adjuvant (R4Pam2Cys) provides (i) immediate, antigen-independent immunity mediated by the innate immune system and (ii) significant enhancement of antigendependent immunity which exhibits an increased breadth of effector function. Intranasal administration of mice with vaccine formulated with R4Pam2Cys but not vaccine alone provides protection against both homologous and serologically distinct (heterologous) viral strains within a day of administration. Vaccination in the presence of R4Pam2Cys subsequently also induces high levels of systemic IgM, IgG1, and IgG2b antibodies and pulmonary IgA antibodies that inhibit hemagglutination (HA) and neuraminidase (NA) activities of homologous but not heterologous virus. Improved primary virus nucleoprotein (NP)-specific CD8! T cell responses are also induced by the use of R4Pam2Cys and are associated with robust recall responses to provide heterologous protection. These protective effects are demonstrated in wild-type and antibody-deficient animals but not in those depleted of CD8! T cells. Using a contact-dependent virus transmission model, we also found that heterologous virus transmission from vaccinated mice to naive mice is significantly reduced. These results demonstrate the potential of adding a TLR2 agonist to an existing seasonal influenza vaccine to improve its utility by inducing immediate short-term nonspecific antiviral protection and also antigen-specific responses to provide homologous and heterologous immunity.
資料タイプ: article
出現コレクション:雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

提供者: David Charles Jackson


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