Plasmodium falciparum merozoite surface protein 3 is a target of allele-specific immunity and alleles are maintained by natural selection
Plasmodium falciparum merozoite surface protein 3 is a target of allele-specific immunity and alleles are maintained by natural selection
复制标题
DOI：
10.1086/509806
复制
发表时间：
2007-01-15
影响因子：
6.4
通讯作者：
Conway, David J.
中科院分区：
文献类型：
--
作者：
Polley, Spencer D.;Tetteh, Kevin K. A.;Conway, David J.
背景恶性疟原虫裂殖子表面蛋白（MSP）3是一种无性生殖的血液期疟疾疫苗候选抗原。序列多态性将等位基因分为2种主要类型，但这些类型的适应性和免疫学意义尚未确定。101 msp 3等位基因序列从2个人口生活在疟疾流行的地区，并分析了自然选择的证据。重组抗原代表全长序列的不同等位基因类型和一个相对保守的C-末端区域的生产，以评估免疫诱导的抗体反应在小鼠和保护协会自然获得的抗体在一个队列的319冈比亚儿童监测疟疾。基于频率的统计分析表明，多态性保持平衡选择在每个研究的2个群体。用全长MSP 3抗原免疫小鼠主要诱导类型特异性抗体，并且人体中大部分自然获得的MSP 3抗体也可以区分等位基因。在冈比亚儿童中，MSP 3等位基因特异性和保守表位的抗体与预防临床疟疾相关，即使在调整年龄和其他裂殖子抗原抗体的存在后也是如此。一种包含这种有希望的候选抗原的两种主要等位基因类型的疫苗可能特别适用于诱导婴儿和幼儿的保护性免疫。
Background. Plasmodium falciparum merozoite surface protein (MSP) 3 is an asexual blood-stage malaria vaccine candidate antigen. Sequence polymorphisms divide alleles into 2 major types, but the adaptive and immunological significance of the types has not been defined.Methods. One hundred one msp3 allele sequences were sampled from 2 populations living in areas where malaria is endemic and were analyzed for evidence of natural selection. Recombinant antigens representing full-length sequences of different allelic types and a relatively conserved C-terminal region were produced, to evaluate immunization-induced antibody responses in mice and protective associations for naturally acquired antibodies in a cohort of 319 Gambian children under surveillance for malaria.Results. Frequency-based statistical analyses indicated that polymorphisms are maintained by balancing selection in each of the 2 populations studied. Immunization of mice with full-length MSP3 antigens induced predominantly type-specific antibodies, and a large proportion of naturally acquired antibodies to MSP3 in humans also discriminated between the alleles. Among Gambian children, antibodies to allele-specific and conserved epitopes in MSP3 were associated prospectively with protection from clinical malaria, even after adjustment for age and for the presence of antibodies to other merozoite antigens.Conclusions. A vaccine incorporating both major allelic types of this promising candidate antigen could be particularly useful for induction of protective immunity in infants and young children.