Dissecting Polyclonal Vaccine-Induced Humoral Immunity against HIV Using Systems Serology.
Dissecting Polyclonal Vaccine-Induced Humoral Immunity against HIV Using Systems Serology.
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DOI：
10.1016/j.cell.2015.10.027
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发表时间：
2015-11-05
期刊：
影响因子：
64.5
通讯作者：
Alter G
中科院分区：
文献类型：
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作者：
Chung AW;Kumar MP;Arnold KB;Yu WH;Schoen MK;Dunphy LJ;Suscovich TJ;Frahm N;Linde C;Mahan AE;Hoffner M;Streeck H;Ackerman ME;McElrath MJ;Schuitemaker H;Pau MG;Baden LR;Kim JH;Michael NL;Barouch DH;Lauffenburger DA;Alter G
虽然抗体滴度和中和被认为是选择成功疫苗的金标准，但这些参数通常不足以预测保护性免疫。由于抗体介导一系列额外中和Fc功能，当中和不能预测保护时，研究Fc介导的活性可能有助于鉴定免疫相关性和体液保护机制。在这里，我们使用了一种称为系统血清学的综合方法来分析四种HIV疫苗试验中引起的体液反应之间的关系。每种疫苗方案诱导独特的体液“Fc指纹”。此外，对第一个适度保护性HIV疫苗试验RV 144的病例：对照数据的分析指出，免疫复合物组成可能是HIV保护性免疫的基础。因此，疫苗体液指纹的多维关系比较提供了一种独特的方法，用于评估和设计针对病原体的新型疫苗，其中相关的保护仍然难以捉摸。
While antibody titers and neutralization are considered the gold standard for the selection of successful vaccines, these parameters are often inadequate predictors of protective immunity. As antibodies mediate an array of extra-neutralizing Fc-functions, when neutralization fails to predict protection, investigating Fc-mediated activity may help identify immunological correlates and mechanism(s) of humoral protection. Here, we used an integrative approach termed Systems Serology to analyze relationships among humoral responses elicited in four HIV vaccine-trials. Each vaccine regimen induced a unique humoral “Fc-fingerprint”. Moreover, analysis of case:control data from the first moderately protective HIV vaccine trial, RV144, pointed to mechanistic insights into immune complex composition that may underlie protective immunity to HIV. Thus, multi-dimensional relational comparisons of vaccine humoral fingerprints offer a unique approach for the evaluation and design of novel vaccines against pathogens for which correlates of protection remain elusive.