1Division of Global Pediatrics, University of Minnesota, Minneapolis, Minnesota.
2Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, Minnesota.
Am J Trop Med Hyg. 2020 Dec;103(6):2174-2182. doi: 10.4269/ajtmh.18-0805. Epub 2020 Oct 27.
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 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 (R0) 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.
在低传播地区，由于疟疾病例数量有限，很难确定对临床疟疾的免疫保护相关性。我们从肯尼亚高地地区的 5753 个人体中采集了血液样本，在接下来的 6 年中确定了该人群中的疟疾发病率，然后在巢式病例对照研究中比较了在该人群中未出现临床疟疾的个体与出现临床疟疾的个体对 11 种疫苗候选抗原的抗体反应（154 例病例和 462 例对照）。个体通过年龄和村庄进行匹配。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 3D7 株、红细胞结合抗原-175、红细胞结合蛋白-2、裂殖体表面蛋白（MSP）-1 FVO 和 3D7 株、MSP-3 和谷氨酸丰富蛋白（GLURP）N 端非重复（R0）和 C 端重复（R2）区。在调整了潜在的混杂因素后，存在针对 LSA-1、GLURP-R2 或 GLURP-R0 的抗体与降低出现临床疟疾的几率相关（比值比 [OR]，[95%CI] 0.56 [0.36-0.89]、0.56 [0.36-0.87]和 0.77 [0.43-1.02]）。针对 LSA-1、GLURP-R2 和 CSP 的抗体水平与降低出现临床疟疾的几率相关（OR [95%CI]；0.61 [0.41-0.89]、0.60 [0.43-0.84]和 0.49 [0.24-0.99]，抗体水平每增加 10 倍）。存在针对 CSP、GLURP-R0、GLURP-R2 和 LSA-1 的抗体可以最好地预测对临床疟疾的保护作用。在低传播环境中，针对 CSP、GLURP-R0、GLURP-R2 和 LSA-1 的抗体与对临床疟疾的保护作用相关。含有这些抗原的疫苗应在低疟疾传播地区进行评估。
