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Vaccine. 2017 Oct 9;35(42):5644-5652. doi: 10.1016/j.vaccine.2017.08.061. Epub 2017 Sep 13.

Hemagglutinin-specific CD4+ T-cell responses following 2009-pH1N1 inactivated split-vaccine inoculation in humans.

Author information

1
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, China; Shenzhen Key Laboratory of Pathogen and Immunity, Shenzhen Third People's Hospital, Shenzhen, China; Center for Influenza Research and Early-Warning (CASCIRE), Chinese Academy of Sciences, Beijing, China.
2
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
3
Jiangsu Provincial Centre for Disease Prevention and Control, Nanjing, China.
4
National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention (China CDC), Beijing, China.
5
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, China.
6
School of Basic Medical Sciences, Wuhan University, No. 185 Donghu Road, Wuchang District, Wuhan, China.
7
National Cancer Institute/HIV dynamics and replication program, Frederick, MD, USA.
8
Center for Influenza Research and Early-Warning (CASCIRE), Chinese Academy of Sciences, Beijing, China.
9
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS), Beijing, China; National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention (China CDC), Beijing, China; Shenzhen Key Laboratory of Pathogen and Immunity, Shenzhen Third People's Hospital, Shenzhen, China; Center for Influenza Research and Early-Warning (CASCIRE), Chinese Academy of Sciences, Beijing, China; Savaid Medical School, University of Chinese Academy of Sciences, Beijing, China.
10
Jiangsu Provincial Centre for Disease Prevention and Control, Nanjing, China. Electronic address: jszfc@vip.sina.com.
11
National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention (China CDC), Beijing, China; Shenzhen Key Laboratory of Pathogen and Immunity, Shenzhen Third People's Hospital, Shenzhen, China. Electronic address: liujun@ivdc.chinacdc.cn.

Abstract

Influenza A virus remains a major threat to public health, and the inactivated split-virus vaccine is the most prevalent vaccine used worldwide. However, our knowledge about cellular immune responses to the inactivated influenza virus vaccine and its correlation with humoral responses are yet limited, which has restricted our understanding of the vaccine's protective mechanisms. Herein, in two clinical trials, T-cell responses specific for both previously identified human leucocyte antigen (HLA)-I-restricted epitopes from influenza virus and hemagglutinin (HA) protein were longitudinally investigated before, during, and after a two-dose vaccination with the inactivated 2009 pandemic H1N1 (2009-pH1N1) vaccine. A robust antibody response in all of the donors after vaccination was observed. Though no CD8+ T-cell responses to known epitopes were detected, HA-specific T-cell responses were primed following vaccination, and the responses were found to be mainly CD4+ T-cell dependent. However, HA-specific T-cells circulating in peripheral blood dropped to baseline levels 6weeks after vaccination, but humoral immune responses maintained a high level for 4months post-vaccination. Significant correlations between the magnitude of the HA-specific T-cell responses and hemagglutination inhibition antibody titers were demonstrated, indicating a priming role of HA-specific T-cells for humoral immune responses. In conclusion, our study indicates that HA-specific CD4+ T-cell responses can be primed by the inactivated 2009-pH1N1 vaccine, which may coordinate with the elicitation of antibody protection. These findings would benefit a better understanding of the immune protective mechanisms of the widely used inactivated 2009-pH1N1 vaccine.

KEYWORDS:

2009 pandemic influenza A (H1N1) virus; HA-specific CD4(+) T-cell response; Split-virus vaccine

PMID:
28917539
DOI:
10.1016/j.vaccine.2017.08.061
[Indexed for MEDLINE]

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