Original Research ARTICLE
Improved Immune Responses in Young and Aged Mice with Adjuvanted Vaccines against H1N1 Influenza Infection
- 1Infectious Disease Research Institute, United States
- 2Center on Aging and Department of Immunology, University of Connecticut School of Medicine, United States
- 3Department of Global Health, University of Washington, United States
- 4PAI Life Sciences (United States), United States
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 (Th1) cells, germinal center (GC) B cells and long-lived bone marrow plasma cells (BMPCs) 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 dendritic cells (BMDCs) 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.
Keywords: influenza, Vaccine, adjuvant, Elderly, T helper 1, H1N1
Received: 12 Sep 2017;
Accepted: 01 Feb 2018.
Edited by:Rino Rappuoli, GSK Vaccines, Italy
Reviewed by:Katie L. Flanagan, RMIT University, Australia
Randy A. Albrecht, Icahn School of Medicine at Mount Sinai, United States
Copyright: © 2018 Baldwin, Hsu, Van Hoeven, Gage, Granger, Guderian, Larsen, Lorenzo, Haynes, Reed and Coler. 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.
* Correspondence: PhD. Rhea N. Coler, Infectious Disease Research Institute, Seattle, WA, United States, Rhea.Coler@idri.org