Center for Global Health and Diseases, Case Western Reserve University, Cleveland, Ohio, USA.
J Infect Dis. 2013 Jul;208(1):149-58. doi: 10.1093/infdis/jit134. Epub 2013 Mar 28.
Acquired immunity to malaria develops with increasing age and repeated infections. Understanding immune correlates of protection from malaria would facilitate vaccine development and identification of biomarkers that reflect changes in susceptibility resulting from ongoing malaria control efforts.
The relationship between immunoglobulin G (IgG) antibody and both interferon γ (IFN-γ) and interleukin 10 (IL-10) responses to the 42-kD C-terminal fragment of Plasmodium falciparum merozoite surface protein 1 (MSP142) and the risk of (re)infection were examined following drug-mediated clearance of parasitemia in 94 adults and 95 children in an area of holoendemicity of western Kenya.
Positive IFN-γ enzyme-linked immunosorbent assay (ELISA) and enzyme-linked immunosorbent spot assay (ELISPOT) responses to MSP142 3D7 were associated with delayed time to (re)infection, whereas high-titer IgG antibodies to MSP142 3D7 or FVO alleles were not independently predictive of the risk of (re)infection. When IFN-γ and IL-10 responses were both present, the protective effect of IFN-γ was abrogated. A Cox proportional hazard model including IFN-γ, IL-10, MSP142 3D7 IgG antibody responses, hemoglobin S genotype, age, and infection status at baseline showed that the time to blood-stage infection correlated positively with IFN-γ responses and negatively with IL-10 responses, younger age, and asymptomatic parasitemia.
Evaluating combined allele-specific cellular and humoral immunity elicited by malaria provides a more informative measure of protection relative to evaluation of either measure alone.
疟疾获得性免疫随年龄增长和重复感染而增强。了解疟疾保护性免疫相关因素有助于疫苗开发和鉴定反映因持续疟疾控制措施而导致的易感性变化的生物标志物。
在肯尼亚西部疟疾高度流行地区，94 名成年人和 95 名儿童经药物清除疟原虫后，研究了 IgG 抗体以及 IFN-γ和白细胞介素 10（IL-10）对恶性疟原虫裂殖体表面蛋白 1（MSP142）42kD C 端片段的反应与（再）感染风险之间的关系。
MSP142 3D7 的 IFN-γ酶联免疫吸附试验（ELISA）和酶联免疫斑点试验（ELISPOT）阳性反应与（再）感染的延迟时间相关，而 MSP142 3D7 或 FVO 等位基因的高滴度 IgG 抗体与（再）感染风险无独立相关性。当 IFN-γ和 IL-10 反应均存在时，IFN-γ的保护作用被消除。包含 IFN-γ、IL-10、MSP142 3D7 IgG 抗体反应、血红蛋白 S 基因型、年龄和基线时感染状态的 Cox 比例风险模型显示，血期感染时间与 IFN-γ反应呈正相关，与 IL-10 反应呈负相关，与年龄较小和无症状性疟原虫血症相关。
评估疟疾诱导的特定等位基因的细胞和体液免疫联合反应相对于单独评估任何一种反应提供了更有信息的保护措施衡量指标。
