Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Pestes 1374, 05508-900 São Paulo (SP), Brazil.
Infect Genet Evol. 2010 Mar;10(2):298-303. doi: 10.1016/j.meegid.2010.01.006. Epub 2010 Jan 25.
The circumsporozoite protein (CSP) of Plasmodium vivax, a major target for malaria vaccine development, has immunodominant B-cell epitopes mapped to central nonapeptide repeat arrays. To determine whether rearrangements of repeat motifs during mitotic DNA replication of parasites create significant CSP diversity under conditions of low effective meiotic recombination rates, we examined csp alleles from sympatric P. vivax isolates systematically sampled from an area of low malaria endemicity in Brazil over a period of 14 months. Nine unique csp types, comprising six different nonapeptide repeats, were observed in 45 isolates analyzed. Identical or nearly identical repeats predominated in most arrays, consistent with their recent expansion. We found strong linkage disequilibrium at sites across the chromosome 8 segment flanking the csp locus, consistent with rare meiotic recombination in this region. We conclude that CSP repeat diversity may not be severely constrained by rare meiotic recombination in areas of low malaria endemicity. New repeat variants may be readily created by nonhomologous recombination even when meiotic recombination is rare, with potential implications for CSP-based vaccine development.
间日疟原虫（Plasmodium vivax）的环子孢子蛋白（CSP）是疟疾疫苗开发的主要靶标，其具有免疫显性 B 细胞表位，映射到中央九肽重复序列。为了确定在低有效减数分裂重组率的条件下，寄生虫有丝分裂 DNA 复制过程中的重复基序重排是否会产生显著的 CSP 多样性，我们系统地检查了来自巴西低疟疾流行地区的 14 个月内采集的共生间日疟原虫分离株中的 csp 等位基因。在分析的 45 个分离株中观察到了 9 种独特的 csp 类型，包括 6 种不同的九肽重复。大多数阵列中以相同或几乎相同的重复为主，这与其最近的扩展一致。我们在 csp 基因座侧翼的染色体 8 片段上的多个位点发现了强烈的连锁不平衡，这与该区域罕见的减数分裂重组一致。我们得出的结论是，在低疟疾流行地区，CSP 重复多样性可能不会受到罕见减数分裂重组的严重限制。即使减数分裂重组很少，新的重复变体也可以通过非同源重组轻松产生，这可能对基于 CSP 的疫苗开发产生影响。
