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Improved Immune Responses in Young and Aged Mice with Adjuvanted Vaccines against H1N1 Influenza Infection

Elderly people are at high risk for influenza-related morbidity and mortality due to progressive immunosenescence. While toll-like receptor (TLR) agonist containing adjuvants, and other adjuvants, have been shown to enhance influenza vaccine-induced protective responses, the mechanisms underlying ho...

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Autores principales: Baldwin, Susan L., Hsu, Fan-Chi, Van Hoeven, Neal, Gage, Emily, Granger, Brian, Guderian, Jeffrey A., Larsen, Sasha E., Lorenzo, Erica C., Haynes, Laura, Reed, Steven G., Coler, Rhea N.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5826078/
https://www.ncbi.nlm.nih.gov/pubmed/29515589
http://dx.doi.org/10.3389/fimmu.2018.00295
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author Baldwin, Susan L.
Hsu, Fan-Chi
Van Hoeven, Neal
Gage, Emily
Granger, Brian
Guderian, Jeffrey A.
Larsen, Sasha E.
Lorenzo, Erica C.
Haynes, Laura
Reed, Steven G.
Coler, Rhea N.
author_facet Baldwin, Susan L.
Hsu, Fan-Chi
Van Hoeven, Neal
Gage, Emily
Granger, Brian
Guderian, Jeffrey A.
Larsen, Sasha E.
Lorenzo, Erica C.
Haynes, Laura
Reed, Steven G.
Coler, Rhea N.
author_sort Baldwin, Susan L.
collection PubMed
description Elderly people are at high risk for influenza-related morbidity and mortality due to progressive immunosenescence. While toll-like receptor (TLR) agonist containing adjuvants, and other adjuvants, have been shown to enhance influenza vaccine-induced protective responses, the mechanisms underlying how these adjuvanted vaccines could benefit the elderly remain elusive. Here, we show that a split H1N1 influenza vaccine (sH1N1) combined with a TLR4 agonist, glucopyranosyl lipid adjuvant formulated in a stable oil-in-water emulsion (GLA-SE), boosts IgG2c:IgG1 ratios, enhances hemagglutination inhibition (HAI) titers, and increases protection in aged mice. We find that all adjuvanted sH1N1 vaccines tested were able to protect both young and aged mice from lethal A/H1N1/California/4/2009 virus challenge after two immunizations compared to vaccine alone. We show that GLA-SE combined with sH1N1, however, also provides enhanced protection from morbidity in aged mice given one immunization (based on change in weight percentage). While the GLA-SE-adjuvanted sH1N1 vaccine promotes the generation of cytokine-producing T helper 1 cells, germinal center B cells, and long-lived bone marrow plasma cells in young mice, these responses were muted in aged mice. Differential in vitro responses, dependent on age, were also observed from mouse-derived bone marrow-derived dendritic cells and lung homogenates following stimulation with adjuvants, including GLA-SE. Besides enhanced HAI titers, additional protective factors elicited with sH1N1 + GLA-SE in young mice were observed, including (a) rapid reduction of viral titers in the lung, (b) prevention of excessive lung inflammation, and (c) homeostatic maintenance of alveolar macrophages (AMs) following H1N1 infection. Collectively, our results provide insight into mechanisms of adjuvant-mediated immune protection in the young and elderly.
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spelling pubmed-58260782018-03-07 Improved Immune Responses in Young and Aged Mice with Adjuvanted Vaccines against H1N1 Influenza Infection Baldwin, Susan L. Hsu, Fan-Chi Van Hoeven, Neal Gage, Emily Granger, Brian Guderian, Jeffrey A. Larsen, Sasha E. Lorenzo, Erica C. Haynes, Laura Reed, Steven G. Coler, Rhea N. Front Immunol Immunology Elderly people are at high risk for influenza-related morbidity and mortality due to progressive immunosenescence. While toll-like receptor (TLR) agonist containing adjuvants, and other adjuvants, have been shown to enhance influenza vaccine-induced protective responses, the mechanisms underlying how these adjuvanted vaccines could benefit the elderly remain elusive. Here, we show that a split H1N1 influenza vaccine (sH1N1) combined with a TLR4 agonist, glucopyranosyl lipid adjuvant formulated in a stable oil-in-water emulsion (GLA-SE), boosts IgG2c:IgG1 ratios, enhances hemagglutination inhibition (HAI) titers, and increases protection in aged mice. We find that all adjuvanted sH1N1 vaccines tested were able to protect both young and aged mice from lethal A/H1N1/California/4/2009 virus challenge after two immunizations compared to vaccine alone. We show that GLA-SE combined with sH1N1, however, also provides enhanced protection from morbidity in aged mice given one immunization (based on change in weight percentage). While the GLA-SE-adjuvanted sH1N1 vaccine promotes the generation of cytokine-producing T helper 1 cells, germinal center B cells, and long-lived bone marrow plasma cells in young mice, these responses were muted in aged mice. Differential in vitro responses, dependent on age, were also observed from mouse-derived bone marrow-derived dendritic cells and lung homogenates following stimulation with adjuvants, including GLA-SE. Besides enhanced HAI titers, additional protective factors elicited with sH1N1 + GLA-SE in young mice were observed, including (a) rapid reduction of viral titers in the lung, (b) prevention of excessive lung inflammation, and (c) homeostatic maintenance of alveolar macrophages (AMs) following H1N1 infection. Collectively, our results provide insight into mechanisms of adjuvant-mediated immune protection in the young and elderly. Frontiers Media S.A. 2018-02-19 /pmc/articles/PMC5826078/ /pubmed/29515589 http://dx.doi.org/10.3389/fimmu.2018.00295 Text en Copyright © 2018 Baldwin, Hsu, Van Hoeven, Gage, Granger, Guderian, Larsen, Lorenzo, Haynes, Reed and Coler. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Baldwin, Susan L.
Hsu, Fan-Chi
Van Hoeven, Neal
Gage, Emily
Granger, Brian
Guderian, Jeffrey A.
Larsen, Sasha E.
Lorenzo, Erica C.
Haynes, Laura
Reed, Steven G.
Coler, Rhea N.
Improved Immune Responses in Young and Aged Mice with Adjuvanted Vaccines against H1N1 Influenza Infection
title Improved Immune Responses in Young and Aged Mice with Adjuvanted Vaccines against H1N1 Influenza Infection
title_full Improved Immune Responses in Young and Aged Mice with Adjuvanted Vaccines against H1N1 Influenza Infection
title_fullStr Improved Immune Responses in Young and Aged Mice with Adjuvanted Vaccines against H1N1 Influenza Infection
title_full_unstemmed Improved Immune Responses in Young and Aged Mice with Adjuvanted Vaccines against H1N1 Influenza Infection
title_short Improved Immune Responses in Young and Aged Mice with Adjuvanted Vaccines against H1N1 Influenza Infection
title_sort improved immune responses in young and aged mice with adjuvanted vaccines against h1n1 influenza infection
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5826078/
https://www.ncbi.nlm.nih.gov/pubmed/29515589
http://dx.doi.org/10.3389/fimmu.2018.00295
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