Division of Population Health and Immunity, Walter and Eliza Hall Institute, Parkville, Australia.
Department of Medical Biology, University of Melbourne, Parkville, Australia.
Elife. 2017 Sep 26;6:e28673. doi: 10.7554/eLife.28673.
The study of antigenic targets of naturally-acquired immunity is essential to identify and prioritize antigens for further functional characterization. We measured total IgG antibodies to 38 antigens, investigating their relationship with prospective risk of malaria in a cohort of 1-3 years old Papua New Guinean children. Using simulated annealing algorithms, the potential protective efficacy of antibodies to multiple antigen-combinations, and the antibody thresholds associated with protection were investigated for the first time. High antibody levels to multiple known and newly identified proteins were strongly associated with protection (IRR 0.44-0.74, p<0.001-0.041). Among five-antigen combinations with the strongest protective effect (>90%), EBP, DBPII, RBP1a, CyRPA, and PVX_081550 were most frequently identified; several of them requiring very low antibody levels to show a protective association. These data identify individual antigens that should be prioritized for further functional testing and establish a clear path to testing a multicomponent vaccine.
研究自然获得性免疫的抗原靶标对于鉴定和优先选择进一步功能表征的抗原至关重要。我们测量了 38 种抗原的总 IgG 抗体，以调查它们与巴布亚新几内亚 1-3 岁儿童队列中疟疾前瞻性风险的关系。使用模拟退火算法，首次研究了针对多种抗原组合的抗体的潜在保护效力以及与保护相关的抗体阈值。针对多种已知和新鉴定的蛋白质的高抗体水平与保护呈强相关（IRR 0.44-0.74，p<0.001-0.041）。在具有最强保护作用的五种抗原组合（>90%）中，EBP、DBPII、RBP1a、CyRPA 和 PVX_081550 最常被鉴定出来；其中有几个需要非常低的抗体水平才能显示出保护相关性。这些数据确定了应优先进行进一步功能测试的个体抗原，并为测试多组分疫苗建立了明确的途径。
