PDF(Sci-hub)
Abstract：
Influenza vaccination is a common approach to prevent seasonal and pandemic influenza. Pre-existing antibodies against close viral strains might impair antibody formation against previously unseen strains-a process called original antigenic sin. The role of this pre-existing cellular immunity in this process is, despite some hints from animal models, not clear. Here, we analyzed cellular and humoral immunity in healthy individuals before and after vaccination with seasonal influenza vaccine. Based on influenza-specific hemagglutination inhibiting (HI) titers, vaccinees were grouped into HI-negative and -positive cohorts followed by in-depth cytometric and TCR repertoire analysis. Both serological groups revealed cross-reactive T-cell memory to the vaccine strains at baseline that gave rise to the majority of vaccine-specific T-cells post vaccination. On the contrary, very limited number of vaccine-specific T-cell clones was recruited from the naive pool. Furthermore, baseline quantity of vaccine-specific central memory helper T-cells and clonotype richness of this population directly correlated with the vaccination efficacy. Our findings suggest that the deliberate recruitment of pre-existing cross-reactive cellular memory might help to improve vaccination outcome.
摘要：
流感疫苗接种是预防季节性和大流行性流感的常用方法。针对紧密病毒株的预先存在的抗体可能会损害针对先前未见过的株的抗体形成-该过程称为原始抗原罪。这种预先存在的细胞免疫在这个过程中的作用是，尽管有一些动物模型的提示,不清楚。这里,我们分析了健康个体接种季节性流感疫苗前后的细胞免疫和体液免疫.基于流感特异性血凝抑制（HI）滴度，将疫苗接种者分为HI阴性和阳性队列,然后进行深入的细胞计数和TCR库分析.两个血清学组都显示出在基线时与疫苗株的交叉反应性T细胞记忆，这在疫苗接种后产生了大多数疫苗特异性T细胞。相反,从初始样本池中招募的疫苗特异性T细胞克隆数量非常有限.此外，该人群疫苗特异性中枢记忆辅助性T细胞的基线数量和克隆型丰富度与疫苗接种效果直接相关.我们的研究结果表明，有意招募预先存在的交叉反应性细胞记忆可能有助于改善疫苗接种结果。
