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Intranasal Vaccination Promotes Detrimental Th17-Mediated Immunity against Influenza Infection

Influenza disease is a global health issue that causes significant morbidity and mortality through seasonal epidemics. Currently, inactivated influenza virus vaccines given intramuscularly or live attenuated influenza virus vaccines administered intranasally are the only approved options for vaccina...

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Autores principales: Maroof, Asher, Yorgensen, Yvonne M., Li, Yufeng, Evans, Jay T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3900655/
https://www.ncbi.nlm.nih.gov/pubmed/24465206
http://dx.doi.org/10.1371/journal.ppat.1003875
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author Maroof, Asher
Yorgensen, Yvonne M.
Li, Yufeng
Evans, Jay T.
author_facet Maroof, Asher
Yorgensen, Yvonne M.
Li, Yufeng
Evans, Jay T.
author_sort Maroof, Asher
collection PubMed
description Influenza disease is a global health issue that causes significant morbidity and mortality through seasonal epidemics. Currently, inactivated influenza virus vaccines given intramuscularly or live attenuated influenza virus vaccines administered intranasally are the only approved options for vaccination against influenza virus in humans. We evaluated the efficacy of a synthetic toll-like receptor 4 agonist CRX-601 as an adjuvant for enhancing vaccine-induced protection against influenza infection. Intranasal administration of CRX-601 adjuvant combined with detergent split-influenza antigen (A/Uruguay/716/2007 (H3N2)) generated strong local and systemic immunity against co-administered influenza antigens while exhibiting high efficacy against two heterotypic influenza challenges. Intranasal vaccination with CRX-601 adjuvanted vaccines promoted antigen-specific IgG and IgA antibody responses and the generation of polyfunctional antigen-specific Th17 cells (CD4(+)IL-17A(+)TNFα(+)). Following challenge with influenza virus, vaccinated mice transiently exhibited increased weight loss and morbidity during early stages of disease but eventually controlled infection. This disease exacerbation following influenza infection in vaccinated mice was dependent on both the route of vaccination and the addition of the adjuvant. Neutralization of IL-17A confirmed a detrimental role for this cytokine during influenza infection. The expansion of vaccine-primed Th17 cells during influenza infection was also accompanied by an augmented lung neutrophilic response, which was partially responsible for mediating the increased morbidity. This discovery is of significance in the field of vaccinology, as it highlights the importance of both route of vaccination and adjuvant selection in vaccine development
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spelling pubmed-39006552014-01-24 Intranasal Vaccination Promotes Detrimental Th17-Mediated Immunity against Influenza Infection Maroof, Asher Yorgensen, Yvonne M. Li, Yufeng Evans, Jay T. PLoS Pathog Research Article Influenza disease is a global health issue that causes significant morbidity and mortality through seasonal epidemics. Currently, inactivated influenza virus vaccines given intramuscularly or live attenuated influenza virus vaccines administered intranasally are the only approved options for vaccination against influenza virus in humans. We evaluated the efficacy of a synthetic toll-like receptor 4 agonist CRX-601 as an adjuvant for enhancing vaccine-induced protection against influenza infection. Intranasal administration of CRX-601 adjuvant combined with detergent split-influenza antigen (A/Uruguay/716/2007 (H3N2)) generated strong local and systemic immunity against co-administered influenza antigens while exhibiting high efficacy against two heterotypic influenza challenges. Intranasal vaccination with CRX-601 adjuvanted vaccines promoted antigen-specific IgG and IgA antibody responses and the generation of polyfunctional antigen-specific Th17 cells (CD4(+)IL-17A(+)TNFα(+)). Following challenge with influenza virus, vaccinated mice transiently exhibited increased weight loss and morbidity during early stages of disease but eventually controlled infection. This disease exacerbation following influenza infection in vaccinated mice was dependent on both the route of vaccination and the addition of the adjuvant. Neutralization of IL-17A confirmed a detrimental role for this cytokine during influenza infection. The expansion of vaccine-primed Th17 cells during influenza infection was also accompanied by an augmented lung neutrophilic response, which was partially responsible for mediating the increased morbidity. This discovery is of significance in the field of vaccinology, as it highlights the importance of both route of vaccination and adjuvant selection in vaccine development Public Library of Science 2014-01-23 /pmc/articles/PMC3900655/ /pubmed/24465206 http://dx.doi.org/10.1371/journal.ppat.1003875 Text en © 2014 Maroof et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Maroof, Asher
Yorgensen, Yvonne M.
Li, Yufeng
Evans, Jay T.
Intranasal Vaccination Promotes Detrimental Th17-Mediated Immunity against Influenza Infection
title Intranasal Vaccination Promotes Detrimental Th17-Mediated Immunity against Influenza Infection
title_full Intranasal Vaccination Promotes Detrimental Th17-Mediated Immunity against Influenza Infection
title_fullStr Intranasal Vaccination Promotes Detrimental Th17-Mediated Immunity against Influenza Infection
title_full_unstemmed Intranasal Vaccination Promotes Detrimental Th17-Mediated Immunity against Influenza Infection
title_short Intranasal Vaccination Promotes Detrimental Th17-Mediated Immunity against Influenza Infection
title_sort intranasal vaccination promotes detrimental th17-mediated immunity against influenza infection
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3900655/
https://www.ncbi.nlm.nih.gov/pubmed/24465206
http://dx.doi.org/10.1371/journal.ppat.1003875
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