Department of Parasitology, Biomedical Primate Research Centre, Postbox 3306, 2280, GH Rijswijk, The Netherlands.
BMC Infect Dis. 2012 Feb 2;12:32. doi: 10.1186/1471-2334-12-32.
Establishing antibody correlates of protection against malaria in human field studies and clinical trials requires, amongst others, an accurate estimation of antibody levels. For polymorphic antigens such as apical membrane antigen 1 (AMA1), this may be confounded by the occurrence of a large number of allelic variants in nature.
To test this hypothesis, plasma antibody levels in an age-stratified cohort of naturally exposed children from a malaria-endemic area in Southern Ghana were determined by indirect ELISA. Titres against four single PfAMA1 alleles were compared with those against three different allele mixtures presumed to have a wider repertoire of epitope specificities. Associations of antibody levels with the incidence of clinical malaria as well as with previous exposure to parasites were also examined.
Antibody titres against PfAMA1 alleles generally increased with age/exposure while antibody specificity for PfAMA1 variants decreased, implying that younger children (≤ 5 years) elicit a more strain-specific antibody response compared to older children. Antibody titre measurements against the FVO and 3D7 AMA1 alleles gave the best titre estimates as these varied least in pair-wise comparisons with titres against all PfAMA1 allele mixtures. There was no association between antibody levels against any capture antigen and either clinical malaria incidence or parasite density.
The current data shows that levels of naturally acquired antigen-specific antibodies, especially in infants and young children, are dependent on the antigenic allele used for measurement. This may be relevant to the interpretation of antibody titre data from measurements against single PfAMA1 alleles, especially in studies involving infants and young children who have experienced fewer infections.
在人体现场研究和临床试验中，建立针对疟疾的保护性抗体相关性，除其他外，还需要准确估计抗体水平。对于诸如顶膜抗原 1（AMA1）等多态抗原，这可能会因自然界中存在大量等位基因变异而受到干扰。
为了检验这一假设，我们通过间接 ELISA 法测定了来自加纳南部疟疾流行地区的年龄分层自然暴露儿童队列中的血浆抗体水平。针对四个单 PfAMA1 等位基因的效价与针对三种不同等位基因混合物的效价进行了比较，这些混合物假定具有更广泛的表位特异性。还检查了抗体水平与临床疟疾发生率以及与先前寄生虫暴露的关联。
PfAMA1 等位基因的抗体效价通常随年龄/暴露而增加，而 PfAMA1 变体的抗体特异性降低，这表明年幼的儿童（≤ 5 岁）与年长的儿童相比，产生更具菌株特异性的抗体反应。针对 FVO 和 3D7 AMA1 等位基因的抗体效价测量可得出最佳效价估计值，因为这些效价在与所有 PfAMA1 等位基因混合物的效价进行两两比较时变化最小。针对任何捕获抗原的抗体水平与临床疟疾发生率或寄生虫密度均无关联。
目前的数据表明，自然获得的针对特定抗原的抗体水平，尤其是在婴儿和幼儿中，取决于用于测量的抗原等位基因。这可能与针对单个 PfAMA1 等位基因的抗体效价数据的解释有关，特别是在涉及经历较少感染的婴儿和幼儿的研究中。
