Chung Amy W, Kumar Manu P, Arnold Kelly B, Yu Wen Han, Schoen Matthew K, Dunphy Laura J, Suscovich Todd J, Frahm Nicole, Linde Caitlyn, Mahan Alison E, Hoffner Michelle, Streeck Hendrik, Ackerman Margaret E, McElrath M Juliana, Schuitemaker Hanneke, Pau Maria G, Baden Lindsey R, Kim Jerome H, Michael Nelson L, Barouch Dan H, Lauffenburger Douglas A, Alter Galit
Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Department of Microbiology and Immunology, Peter Doherty Institute, University of Melbourne, Parkville, VIC 3010, Australia.
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Cell. 2015 Nov 5;163(4):988-98. doi: 10.1016/j.cell.2015.10.027.
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.
虽然抗体滴度和中和作用被认为是成功疫苗筛选的金标准，但这些参数往往不足以预测保护性免疫。由于抗体介导一系列额外的中和性Fc功能，当中和作用无法预测保护效果时，研究Fc介导的活性可能有助于识别体液保护的免疫相关因素和机制。在这里，我们使用一种称为系统血清学的综合方法来分析四项HIV疫苗试验中引发的体液反应之间的关系。每种疫苗方案都诱导出独特的体液“Fc指纹”。此外，对首个具有中度保护作用的HIV疫苗试验RV144的病例对照数据进行分析，揭示了免疫复合物组成的机制性见解，这些见解可能是HIV保护性免疫的基础。因此，疫苗体液指纹的多维关系比较为评估和设计针对保护相关因素仍难以捉摸的病原体的新型疫苗提供了一种独特的方法。
