Infectious Diseases Unit, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden.
Clin Infect Dis. 2013 Nov;57(10):1409-16. doi: 10.1093/cid/cit556. Epub 2013 Aug 27.
Elucidating the mechanisms of naturally acquired immunity to Plasmodium falciparum infections would be highly valuable for malaria vaccine development. Asymptomatic multiclonal infections have been shown to predict protection from clinical malaria in a transmission-dependent manner, but the mechanisms underlying this are unclear. We assessed the breadth of antibody responses to several vaccine candidate merozoite antigens in relation to the infecting parasite population and clinical immunity.
In a cohort study in Tanzania, 320 children aged 1-16 years who were asymptomatic at baseline were included. We genotyped P. falciparum infections by targeting the msp2 gene using polymerase chain reaction and capillary electrophoresis and measured antibodies to 7 merozoite antigens using a multiplex assay. We assessed the correlation between the number of clones and the breadth of the antibody response, and examined their effects on the risk of malaria during 40 weeks of follow-up using age-adjusted multivariate regression models.
The antibody breadth was positively correlated with the number of clones (RR [risk ratio], 1.63; 95% confidence interval [CI], 1.32-2.02). Multiclonal infections were associated with a nonsignificant reduction in the risk of malaria in the absence of antibodies (RR, 0.83; 95% CI, .29-2.34). The breadth of the antibody response was significantly associated with a reduced risk of malaria in the absence of infections (RR, 0.25; 95% CI, .09-.66). In combination, these factors were associated with a lower risk of malaria than they were individually (RR, 0.14; 95% CI, .04-.48).
These data suggest that malaria vaccines mimicking naturally acquired immunity should ideally induce antibody responses that can be boosted by natural infections.
阐明人体对疟原虫感染产生自然免疫力的机制，对于疟疾疫苗的开发将具有重要意义。无症状的多克隆感染已被证明可以以依赖传播的方式预测对临床疟疾的保护，但其中的机制尚不清楚。我们评估了针对几种候选疟原虫裂殖子抗原的抗体反应广度与感染寄生虫群体和临床免疫力的关系。
在坦桑尼亚的一项队列研究中，纳入了 320 名基线时无症状的 1-16 岁儿童。我们通过聚合酶链反应和毛细管电泳靶向 msp2 基因对疟原虫感染进行基因分型，并使用多重分析测定法测量 7 种裂殖子抗原的抗体。我们评估了克隆数量与抗体反应广度之间的相关性，并使用年龄调整的多变量回归模型，在 40 周的随访期间，检查了它们对疟疾风险的影响。
抗体广度与克隆数量呈正相关（RR[风险比]，1.63；95%置信区间[CI]，1.32-2.02）。在没有抗体的情况下，多克隆感染与疟疾风险的降低呈非显著相关（RR，0.83；95%CI，.29-2.34）。在没有感染的情况下，抗体反应的广度与疟疾风险的降低显著相关（RR，0.25；95%CI，.09-.66）。综合来看，这些因素与疟疾的风险比它们单独的情况要低（RR，0.14；95%CI，.04-.48）。
这些数据表明，模拟自然获得性免疫的疟疾疫苗理想情况下应诱导可被自然感染增强的抗体反应。
