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Vaccines (Basel). 2018 Sep 20;6(4). pii: E66. doi: 10.3390/vaccines6040066.

Virus-Like Particles Are a Superior Platform for Presenting M2e Epitopes to Prime Humoral and Cellular Immunity against Influenza Virus.

Author information

1
Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA. kihyekim4282@gmail.com.
2
Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA. ymankwon@gmail.com.
3
Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA. leechard75@gmail.com.
4
Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA. mckim001@gmail.com.
5
Komipharm Co., Ltd., Siheung, Gyeonggi-do 15094, Korea. mckim001@gmail.com.
6
Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA. hshwang33@gmail.com.
7
Department of Microbiology, Chonnam National University Medical School, Hwasun-gun, Jeonnam 58128, Korea. hshwang33@gmail.com.
8
Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA. ej.ko226@gmail.com.
9
National Cancer Institute, National Institutes of Health, Bethesda, MD 20850, USA. ej.ko226@gmail.com.
10
Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA. youl6248@gmail.com.
11
Department of Chemical and Materials Engineering, University of Alberta, Edmonton, AB T6G 2V4, Canada. hyojick@ualberta.ca.
12
Institute for Biomedical Sciences, Georgia State University, Atlanta, GA 30303, USA. skang24@gsu.edu.

Abstract

Influenza virus M2 protein has a highly conserved ectodomain (M2e) as a cross-protective antigenic target. We investigated the antigenic and immunogenic properties of tandem repeat M2e (5xM2e) proteins and virus-like particles (5xM2e VLP) to better understand how VLP and protein platform vaccines induce innate and protective adaptive immune responses. Despite the high antigenic properties of 5xM2e proteins, the 5xM2e VLP was superior to 5xM2e proteins in inducing IgG2a isotype antibodies, T cell responses, plasma cells and germinal center B cells as well as in conferring cross protection. Mice primed with 5xM2e VLP were found to be highly responsive to 5xM2e protein boost, overcoming the low immunogenicity and protective efficacy of 5xM2e proteins. Immunogenic differences between VLPs and proteins in priming immune responses might be due to an intrinsic ability of 5xM2e VLP to stimulate dendritic cells secreting T helper type 1 (Th1) cytokines. We also found that 5xM2e VLP was effective in inducing inflammatory cytokines and chemokines, and in recruiting macrophages, monocytes, neutrophils, and CD11b⁺ dendritic cells at the injection site. Therefore, this study provides evidence that 5xM2e VLP is an effective vaccine platform, inducing cross-protection by stimulating innate and adaptive immune responses.

KEYWORDS:

5xM2e epitopes; innate/adaptive immunity; priming effect; virus-like particles (VLP), cross-protection

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