Malaria Immunoepidemiology in Low Transmission: Correlation of Infecting Genotype and Immune Response to Domains of Plasmodium falciparum Merozoite Surface Protein 3
Malaria Immunoepidemiology in Low Transmission: Correlation of Infecting Genotype and Immune Response to Domains of Plasmodium falciparum Merozoite Surface Protein 3
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DOI：
10.1128/iai.01332-10
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发表时间：
2011-05-01
影响因子：
3.1
通讯作者：
Rayner, Julian C.
中科院分区：
文献类型：
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作者：
Jordan, Stephen J.;Oliveira, Ana L.;Rayner, Julian C.
由恶性疟原虫引起的疟疾是全球婴儿死亡的主要原因，目前没有有效的疫苗。已经确定了多种潜在的疫苗靶点，免疫流行病学研究在评估这些候选疫苗方面发挥了重要作用。当在高传播环境中进行此类研究时，个体通常被遗传上不同的恶性疟原虫类型的复杂混合物双重感染，使得不可能将感染抗原的基因型与抗体反应直接关联起来。相反，在低传播的地区，恶性疟原虫感染通常是遗传简单的，感染基因型和抗原特异性免疫反应的直接比较是可能的。作为该方法效用的测试，在秘鲁伊基托斯附近收集的血清样品中测试针对疫苗候选物恶性疟原虫裂殖子表面蛋白3（PfMSP 3）的几个结构域和等位基因变体的应答。识别保守的C-末端和更可变的N-末端结构域的抗体，但抗N-末端反应更普遍，滴度更高，主要是嗜细胞亚类。比较对不同PfMSP 3变体的抗体应答与感染时存在的PfMSP 3基因型显示，抗N末端应答主要是等位基因类别特异性的，但有一些证据表明应答跨等位基因类别交叉反应。当测试一个等位基因类别内的变体时，交叉反应性应答的证据要强得多，这对基于PfMSP 3的基因型超越疫苗的合理开发具有意义。
Malaria caused by Plasmodium falciparum is a major cause of global infant mortality, and no effective vaccine currently exists. Multiple potential vaccine targets have been identified, and immunoepidemiology studies have played a major part in assessing those candidates. When such studies are carried out in high-transmission settings, individuals are often superinfected with complex mixtures of genetically distinct P. falciparum types, making it impossible to directly correlate the genotype of the infecting antigen with the antibody response. In contrast, in regions of low transmission P. falciparum infections are often genetically simple, and direct comparison of infecting genotype and antigen-specific immune responses is possible. As a test of the utility of this approach, responses against several domains and allelic variants of the vaccine candidate P. falciparum merozoite surface protein 3 (PfMSP3) were tested in serum samples collected near Iquitos, Peru. Antibodies recognizing both the conserved C-terminal and the more variable N-terminal domain were identified, but anti-N-terminal responses were more prevalent, of higher titers, and primarily of cytophilic subclasses. Comparing antibody responses to different PfMSP3 variants with the PfMSP3 genotype present at the time of infection showed that anti-N-terminal responses were largely allele class specific, but there was some evidence for responses that cross-reacted across allele classes. Evidence for cross-reactive responses was much stronger when variants within one allele class were tested, which has implications for the rational development of genotype-transcending PfMSP3-based vaccines.