Mugyenyi Cleopatra K, Elliott Salenna R, Yap Xi Zen, Feng Gaoqian, Boeuf Philippe, Fegan Gregory, Osier Faith F H, Fowkes Freya J I, Avril Marion, Williams Thomas N, Marsh Kevin, Beeson James G
Kenya Medical Research Institute (KEMRI), Centre for Geographic Medicine, Coast, KEMRI-Wellcome Trust Research Programme, Kilifi.
Burnet Institute, Melbourne.
J Infect Dis. 2017 Oct 17;216(7):887-898. doi: 10.1093/infdis/jix370.
We investigated the poorly understood impact of declining malaria transmission on maintenance of antibodies to Plasmodium falciparum merozoite antigens and infected erythrocytes (IEs), including functional immunity.
In a 3-year longitudinal cohort of 300 Kenyan children, antibodies to different AMA1 and MSP2 alleles of merozoites, IE surface antigens, and antibody functional activities were quantified.
Over a period in which malaria transmission declined markedly, AMA1 and MSP2 antibodies decreased substantially; estimated half-lives of antibody duration were 0.8 year and 1-3 years, respectively. However, 69%-74% of children maintained their seropositivity to AMA1 alleles and 42%-52% to MSP2 alleles. Levels and prevalence of antimerozoite antibodies were consistently associated with increasing age and concurrent parasitemia. Antibodies promoting opsonic phagocytosis of merozoites declined rapidly (half-life, 0.15 years). In contrast, complement-fixing antibodies to merozoites did not decline and antibodies to IE surface antigens expressing virulent phenotypes were much better maintained (half-life, 4-10 years).
A decline in malaria transmission is associated with reduction in naturally acquired immunity. However, loss of immunity is not universal; some key functional responses and antibodies to IEs were better maintained and these may continue to provide some protection. Findings have implications for malaria surveillance and control measures and informing vaccine development.
我们研究了疟疾传播减少对恶性疟原虫裂殖子抗原和感染红细胞（IEs）抗体维持的影响，包括功能性免疫，而这方面的影响此前了解甚少。
在一项对300名肯尼亚儿童进行的为期3年的纵向队列研究中，对裂殖子不同AMA1和MSP2等位基因、IE表面抗原的抗体以及抗体功能活性进行了定量分析。
在疟疾传播显著下降的时期内，AMA1和MSP2抗体大幅减少；抗体持续时间的估计半衰期分别为0.8年和1 - 3年。然而，69% - 74%的儿童对AMA1等位基因保持血清阳性，42% - 52%的儿童对MSP2等位基因保持血清阳性。抗裂殖子抗体的水平和流行率始终与年龄增长和同时期的寄生虫血症相关。促进裂殖子调理吞噬作用的抗体迅速下降（半衰期为0.15年）。相比之下，裂殖子的补体固定抗体没有下降，对表达毒力表型的IE表面抗原的抗体维持得更好（半衰期为4 - 10年）。
疟疾传播减少与自然获得性免疫的降低有关。然而，免疫丧失并非普遍现象；一些关键的功能性反应和针对IEs的抗体维持得更好，这些可能继续提供一定的保护。研究结果对疟疾监测和控制措施以及疫苗研发具有启示意义。
