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.