重磅！中国疾控中心病毒病所在流感疫苗Ｔ细胞免疫方面取得进展

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​中国疾控中心病毒病所高福院士实验室主要从事新发高致病性病毒感染的细胞免疫应答以及新发病毒生态与流行病学的基础和应用性研究。近日，研究团队联合江苏省疾控中心在甲型H1N1流感病毒疫苗的T细胞免疫检测和机制方面取得了进展，相关结果于2017年9月13日在线发表在《Vaccine》杂志上，题为《Hemagglutinin-specificCD4+ T-cell responses following 2009-pH1N1 inactivated split-vaccineinoculation in humans》。病毒病所刘军副研究员与江苏省疾控中心朱凤才副主任为该论文的共同通讯作者。

我国自主研发的2009甲型H1N1流感病毒疫苗是国际上较早获得世卫组织认可的裂解疫苗。研究团队在北京和江苏泰州两地进行了多中心临床研究，对该疫苗接种后的机体免疫应答，尤其是T细胞免疫应答进行了系统评价。

         图1. 流感疫苗接种后的HA蛋白特异性CD4+ T细胞免疫反应。
研究发现血凝素蛋白（Hemagglutinin，HA）特异性CD4+ T细胞在疫苗接种后能够被激发出来，而这些T细胞在疫苗接种6周后下降到基底水平，提示HA特异性CD4+ T细胞的归巢。而HA特异性T细胞水平与其抗体水平具有显著相关性，表明HA特异性T细胞免疫在疫苗接种后体液免疫的产生过程中可能发挥了重要作用。同时，通过MHC四聚体染色表明，疫苗接种后并未激发机体流感特异性CD8+ T细胞免疫反应。这一研究对于理解甲型H1N1流感病毒疫苗的免疫保护机制提供了重要参考，并为改进和优化流感病毒裂解疫苗提供了重要信息。


图2. MHC四聚体技术检测流感特异性CD8+ T细胞免疫反应。
近年来，中国疾控中心病毒病所刘军副研究员在新发病毒T细胞免疫应答及保护机制方面开展了系列研究工作。其中，在针对流感病毒特异性T细胞的研究中，发现甲型H1N1流感病毒广泛存在HLA-A24和-A3超家族分子交叉反应性T细胞表位（J Virol，2012）；流感病毒保守的T细胞表位介导了甲型H1N1流感病毒主要的CD8+ T细胞免疫反应（Eur J Immunol，2013）；在H7N9禽流感病毒方面，发现健康人群广泛存在能够对H7N9流感病毒产生交叉免疫反应的T细胞，并阐明了表位突变影响其免疫原性的分子基础（J Infect Dis，2016）。
这些研究和发现对于我们理解流感病毒感染后机体免疫应答规律及流感病毒的免疫逃逸提供了重要参考，并为开发广谱抗流感疫苗提供了重要思路。
Abstract
Influenza A virus remains a major threat to public health, and theinactivated split-virus vaccine is the most prevalent vaccine used worldwide.However, our knowledge about cellular immune responses to the inactivatedinfluenza virus vaccine and its correlation with humoral responses are yetlimited, which has restricted our understanding of the vaccine’s protectivemechanisms. Herein, in two clinical trials, T-cell responses specific for bothpreviously identified human leucocyte antigen (HLA)-I-restricted epitopes frominfluenza virus and hemagglutinin (HA) protein were longitudinally investigatedbefore, during, and after a two-dose vaccination with the inactivated 2009pandemic H1N1 (2009-pH1N1) vaccine. A robust antibody response in all of thedonors after vaccination was observed. Though no CD8+ T-cellresponses to known epitopes were detected, HA-specific T-cell responses wereprimed following vaccination, and the responses were found to be mainly CD4+ T-celldependent. However, HA-specific T-cells circulating in peripheral blood droppedto baseline levels 6 weeks after vaccination, but humoral immune responsesmaintained a high level for 4 months post-vaccination. Significantcorrelations between the magnitude of the HA-specific T-cell responses andhemagglutination inhibition antibody titers were demonstrated, indicating apriming role of HA-specific T-cells for humoral immune responses.
In conclusion, our study indicates that HA-specific CD4+ T-cellresponses can be primed by the inactivated 2009-pH1N1 vaccine, which maycoordinate with the elicitation of antibody protection. These findings wouldbenefit a better understanding of the immune protective mechanisms of thewidely used inactivated 2009-pH1N1 vaccine.


全文链接：
Vaccine：http://www.sciencedirect.com/sci ... i/S0264410X17311593

相关资料：
JID: https://doi.org/10.1093/infdis/jiw471
EJI:http://onlinelibrary.wiley.com/d ... 487F15ECC51A.f03t04
JVI: http://jvi.asm.org/content/86/24/13281.long