Blockage of regulatory T cells augments induction of protective immune responses by influenza virus-like particles in aged mice

• Type of Material: Article
• Authors: Zhiyuan Wen, Chinese Academy of Agricultural Sciences; Xi Wang, Fourth Military Medical University; Ke Dong, Fourth Military Medical University; Huizhong Zhang, Fourth Military Medical University; Zhigao Bu, Chinese Academy of Agricultural Sciences; Ling Ye, Emory University; Chinglai Yang, Emory University
• Language: English
• Date: 2017-12-01
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2017 Institut Pasteur
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.micinf.2017.08.013
• Title of Journal or Parent Work: Microbes and Infection
• ISSN: 1286-4579
• Volume: 19
• Issue: 12
• Start Page: 626
• End Page: 634
• Grant/Funding Information: Portions of this study was supported by funding from the Emory University Global Health Institute, the National Institutes of Health grant AI06652, and the NIH CEIRS contract HHSN272201400004C
• Keywords: INSECT CELLS; Vaccine; Aging; Immunology; IMMUNOSENESCENCE; HUMAN INFECTION; LIVE; EVOLUTION; Infectious Diseases; VACCINES; Science & Technology; Life Sciences & Biomedicine; VACCINATION; Influenza; Regulatory T cell; ANTI-CD25 MONOCLONAL-ANTIBODY; Microbiology; EFFICACY; A VIRUS
• Research Categories: Biology, Microbiology; Health Sciences, Immunology

Abstract

Elderly humans over 65 years old are at great risk to pathogenesis by influenza virus infection. However, although influenza vaccines provide effective protection in healthy young adults, protection of elderly adults is substantially lower even with a good match between the vaccine and the circulating influenza virus. To gain insight of the underlying mechanism for the reduced immunogenicity of influenza vaccines in the aged population, we investigated immunogenicity of influenza virus-like particle vaccines in aged mice, which represent a useful model for studying aging associated impairment in immune responses. Specifically, we investigated the effect of inhibiting regulatory T cells in aged mice on induction of protective immune responses by influenza vaccines. Our results showed that injecting anti-CD25 antibodies could down-regulate CD25 on the surface of regulatory T cells and significantly increase the levels of antibody responses induced by VLP immunization in aged mice. Further, the profiles of antibody responses were also changed towards Th1 type by regulatory T cell blockage in aged mice. Moreover, aged mice that were treated by anti-CD25 antibodies prior to vaccination were more effectively protected against lethal influenza virus challenge.