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

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

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...

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Main Authors: Chua, Brendon Y., Wong, Chinn Yi, Mifsud, Edin J., Edenborough, Kathryn M., Sekiya, Toshiki, Tan, Amabel C. L., Mercuri, Francesca, Rockman, Steve, Chen, Weisan, Turner, Stephen J., Doherty, Peter C., Kelso, Anne, Brown, Lorena E., Jackson, David C.
Format: Online
Language:English
Published: American Society of Microbiology 2015
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4626850/
id pubmed-4626850
recordtype oai_dc
spelling pubmed-46268502015-11-02 Inactivated Influenza Vaccine That Provides Rapid, Innate-Immune-System-Mediated Protection and Subsequent Long-Term Adaptive Immunity Chua, Brendon Y. Wong, Chinn Yi Mifsud, Edin J. Edenborough, Kathryn M. Sekiya, Toshiki Tan, Amabel C. L. Mercuri, Francesca Rockman, Steve Chen, Weisan Turner, Stephen J. Doherty, Peter C. Kelso, Anne Brown, Lorena E. Jackson, David C. Research Article 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 antigen-dependent 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. American Society of Microbiology 2015-10-27 /pmc/articles/PMC4626850/ /pubmed/26507227 http://dx.doi.org/10.1128/mBio.01024-15 Text en Copyright © 2015 Chua et al. http://creativecommons.org/licenses/by-nc-sa/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-ShareAlike 3.0 Unported license (http://creativecommons.org/licenses/by-nc-sa/3.0/) , which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Chua, Brendon Y.
Wong, Chinn Yi
Mifsud, Edin J.
Edenborough, Kathryn M.
Sekiya, Toshiki
Tan, Amabel C. L.
Mercuri, Francesca
Rockman, Steve
Chen, Weisan
Turner, Stephen J.
Doherty, Peter C.
Kelso, Anne
Brown, Lorena E.
Jackson, David C.
spellingShingle Chua, Brendon Y.
Wong, Chinn Yi
Mifsud, Edin J.
Edenborough, Kathryn M.
Sekiya, Toshiki
Tan, Amabel C. L.
Mercuri, Francesca
Rockman, Steve
Chen, Weisan
Turner, Stephen J.
Doherty, Peter C.
Kelso, Anne
Brown, Lorena E.
Jackson, David C.
Inactivated Influenza Vaccine That Provides Rapid, Innate-Immune-System-Mediated Protection and Subsequent Long-Term Adaptive Immunity
author_facet Chua, Brendon Y.
Wong, Chinn Yi
Mifsud, Edin J.
Edenborough, Kathryn M.
Sekiya, Toshiki
Tan, Amabel C. L.
Mercuri, Francesca
Rockman, Steve
Chen, Weisan
Turner, Stephen J.
Doherty, Peter C.
Kelso, Anne
Brown, Lorena E.
Jackson, David C.
author_sort Chua, Brendon Y.
title Inactivated Influenza Vaccine That Provides Rapid, Innate-Immune-System-Mediated Protection and Subsequent Long-Term Adaptive Immunity
title_short Inactivated Influenza Vaccine That Provides Rapid, Innate-Immune-System-Mediated Protection and Subsequent Long-Term Adaptive Immunity
title_full Inactivated Influenza Vaccine That Provides Rapid, Innate-Immune-System-Mediated Protection and Subsequent Long-Term Adaptive Immunity
title_fullStr Inactivated Influenza Vaccine That Provides Rapid, Innate-Immune-System-Mediated Protection and Subsequent Long-Term Adaptive Immunity
title_full_unstemmed Inactivated Influenza Vaccine That Provides Rapid, Innate-Immune-System-Mediated Protection and Subsequent Long-Term Adaptive Immunity
title_sort inactivated influenza vaccine that provides rapid, innate-immune-system-mediated protection and subsequent long-term adaptive immunity
description 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 antigen-dependent 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.
publisher American Society of Microbiology
publishDate 2015
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4626850/
_version_ 1613495102515183616

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