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

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Title: Inactivated Influenza Vaccine That Provides Rapid, Innate-Immune- System-Mediated Protection and Subsequent Long-Term Adaptive Immunity
Authors: Chua, Brendon Y. Browse this author
Wong, Chinn Yi Browse this author
Mifsud, Edin J. Browse this author
Edenborough, Kathryn M. Browse this author
Sekiya, Toshiki Browse this author
Tan, Amabel C. L. Browse this author
Mercuri, Francesca Browse this author
Rockman, Steve Browse this author
Chen, Weisan Browse this author
Turner, Stephen J. Browse this author
Doherty, Peter C. Browse this author
Kelso, Anne Browse this author
Brown, Lorena E. Browse this author
Jackson, David C. Browse this author
Issue Date: 27-Oct-2015
Publisher: American Society for Microbiology
Journal Title: mBio
Volume: 6
Issue: 6
Start Page: e01024-15
Abstract: 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.
Type: article
Appears in Collections:国際連携研究教育局 : GI-CoRE (Global Institution for Collaborative Research and Education : GI-CoRE) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: David Charles Jackson

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