Malaria Transmission and Immunity in the Kenyan Highlands Antibody Correlates of Protection from Clinical Plasmodium falciparum Malaria in an Area of Low and Unstable Malaria Transmission
Malaria Transmission and Immunity in the Kenyan Highlands Antibody Correlates of Protection from Clinical Plasmodium falciparum Malaria in an Area of Low and Unstable Malaria Transmission
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DOI：
10.4269/ajtmh.18-0805
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发表时间：
2020-12-01
影响因子：
3.3
通讯作者：
John, Chandy
中科院分区：
文献类型：
--
作者：
Hamre, Karen;Ondigo, Bartholomew;John, Chandy
由于疟疾病例数量有限，在低传播地区难以确定预防临床疟疾的免疫相关因素。我们从肯尼亚高原地区的5，753名个体中收集了血液样本，确定了该人群在未来6年内的疟疾发病率，然后在巢式病例对照研究（154例病例和462例对照）中比较了对11种恶性疟原虫疫苗候选抗原的抗体应答。每个人都按年龄和村庄配对。检测的抗原包括环子孢子蛋白（CSP）、肝期抗原（LSA）-1、顶膜抗原-1 FVO和3D 7菌株、红细胞结合抗原-175、红细胞结合蛋白-2、裂殖子表面蛋白（MSP）-1 FVO和3D 7菌株、MSP-3和富含谷氨酸的蛋白（GLURP）N-末端非重复（RO）和C-末端重复（R2）区域。调整潜在混杂因素后，LSA-1、GLURP-R2或GLURP-R 0抗体的存在与临床疟疾发生几率降低相关（比值比[OR]，[95% CI]分别为0.56 [0.36-0.89]、0.56 [0.36-0.87]和0.77 [0.43-1.02]）。LSA-1、GLURP-R2和CSP抗体水平与临床疟疾发病几率降低相关（抗体水平每增加10倍，OR [95% CI]分别为0.61 [0.41-0.89]、0.60 [0.43-0.84]和0.49 [0.24-0.99]）。CSP、GLURP-R 0、GLURP-R2和LSA-1抗体的存在结合了对临床疟疾的最佳预测保护。CSP、GLURP-R 0、GLURP-R2和LSA-1的抗体与在低传播环境中预防临床疟疾有关。含有这些抗原的疫苗应在疟疾低传播地区进行评估。
Immune correlates of protection against clinical malaria are difficult to ascertain in low-transmission areas because of the limited number of malaria cases. We collected blood samples from 5,753 individuals in a Kenyan highland area, ascertained malaria incidence in this population over the next 6 years, and then compared antibody responses to 11 Plasmodium falciparum vaccine candidate antigens in individuals who did versus did not develop clinical malaria in a nested case-control study (154 cases and 462 controls). Individuals were matched by age and village. Antigens tested included circumsporozoite protein (CSP), liver-stage antigen (LSA)-1, apical membrane antigen-1 FVO and 3D7 strains, erythrocyte-binding antigen-175, erythrocyte-binding protein-2, merozoite surface protein (MSP)-1 FVO and 3D7 strains, MSP-3, and glutamate-rich protein (GLURP) N-terminal non-repetitive (RO) and C-terminal repetitive (R2) regions. After adjustment for potential confounding factors, the presence of antibodies to LSA-1, GLURP-R2, or GLURP-R0 was associated with decreased odds of developing clinical malaria (odds ratio [OR], [95% CI] 0.56 [0.36-0.89], 0.56 [0.36-0.87], and 0.77 [0.43-1.02], respectively). Levels of antibodies to LSA-1, GLURP-R2, and CSP were associated with decreased odds of developing clinical malaria (OR [95% CI]; 0.61 [0.41-0.89], 0.60 [0.43-0.84], and 0.49 [0.24-0.99], for every 10-fold increase in antibody levels, respectively). The presence of antibodies to CSP, GLURP-R0, GLURP-R2, and LSA-1 combined best-predicted protection from clinical malaria. Antibodies to CSP, GLURP-R0, GLURP-R2, and LSA-1 are associated with protection against clinical malaria in a low-transmission setting. Vaccines containing these antigens should be evaluated in low malaria transmission areas.