Identification of highly-protective combinations of Plasmodium vivax recombinant proteins for vaccine development.
Identification of highly-protective combinations of Plasmodium vivax recombinant proteins for vaccine development.
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DOI：
10.7554/elife.28673
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发表时间：
2017-09-26
期刊：
影响因子：
7.7
通讯作者：
Mueller I
中科院分区：
文献类型：
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作者：
França CT;White MT;He WQ;Hostetler JB;Brewster J;Frato G;Malhotra I;Gruszczyk J;Huon C;Lin E;Kiniboro B;Yadava A;Siba P;Galinski MR;Healer J;Chitnis C;Cowman AF;Takashima E;Tsuboi T;Tham WH;Fairhurst RM;Rayner JC;King CL;Mueller I
自然获得性免疫的抗原靶点的研究对于识别和优先考虑抗原以进行进一步的功能表征至关重要。我们测量了38种间日疟原虫抗原的总IgG抗体，研究了它们与巴布亚新几内亚1-3岁儿童队列中疟疾潜在风险的关系。使用模拟退火算法，抗体对多种抗原组合的潜在保护效力，以及与保护相关的抗体阈值首次进行了研究。对多种已知和新鉴定的蛋白质的高抗体水平与保护强烈相关（IRR 0.44-0.74，p<0.001-0.041）。在具有最强保护作用（>90%）的五种抗原组合中，EBP、DBPII、RBP 1a、CyRPA和PVX_081550是最常鉴定的;其中几种需要非常低的抗体水平才能显示保护性关联。这些数据确定了应优先进行进一步功能检测的单个抗原，并建立了检测多组分间日疟原虫疫苗的明确途径。
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 P. vivax 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 P. vivax vaccine.