Baum Elisabeth, Badu Kingsley, Molina Douglas M, Liang Xiaowu, Felgner Philip L, Yan Guiyun
Department of Medicine, Division of Infectious Diseases, University of California Irvine, Irvine, California, United States of America.
PLoS One. 2013 Dec 2;8(12):e82246. doi: 10.1371/journal.pone.0082246. eCollection 2013.
Malaria represents a major public health problem in Africa. In the East African highlands, the high-altitude areas were previously considered too cold to support vector population and parasite transmission, rendering the region particularly prone to epidemic malaria due to the lack of protective immunity of the population. Since the 1980's, frequent malaria epidemics have been reported and these successive outbreaks may have generated some immunity against Plasmodium falciparum amongst the highland residents. Serological studies reveal indirect evidence of human exposure to the parasite, and can reliably assess prevalence of exposure and transmission intensity in an endemic area. However, the vast majority of serological studies of malaria have been, hereto, limited to a small number of the parasite's antigens. We surveyed and compared the antibody response profiles of age-stratified sera from residents of two endemic areas in the western Kenyan highlands with differing malaria transmission intensities, during two distinct seasons, against 854 polypeptides of P. falciparum using high-throughput proteomic microarray technology. We identified 107 proteins as serum antibody targets, which were then characterized for their gene ontology biological process and cellular component of the parasite, and showed significant enrichment for categories related to immune evasion, pathogenesis and expression on the host's cell and parasite's surface. Additionally, we calculated age-fitted annual seroconversion rates for the immunogenic proteins, and contrasted the age-dependent antibody acquisition for those antigens between the two sampling sites. We observed highly immunogenic antigens that produce stable antibody responses from early age in both sites, as well as less immunogenic proteins that require repeated exposure for stable responses to develop and produce different seroconversion rates between sites. We propose that a combination of highly and less immunogenic proteins could be used in serological surveys to detect differences in malaria transmission levels, distinguishing sites of unstable and stable transmission.
疟疾是非洲的一个主要公共卫生问题。在东非高地，高海拔地区以前被认为太冷，无法维持媒介种群和寄生虫传播，由于当地人群缺乏保护性免疫力，该地区特别容易发生疟疾流行。自20世纪80年代以来，频繁的疟疾流行时有报道，这些连续的疫情爆发可能使高地居民对恶性疟原虫产生了一定的免疫力。血清学研究揭示了人类接触该寄生虫的间接证据，并能可靠地评估流行地区的接触率和传播强度。然而，迄今为止，绝大多数疟疾血清学研究仅限于少数几种寄生虫抗原。我们使用高通量蛋白质组微阵列技术，在两个不同季节，针对恶性疟原虫的854种多肽，调查并比较了肯尼亚西部高地两个疟疾传播强度不同的流行地区居民按年龄分层的血清抗体反应谱。我们鉴定出107种蛋白质作为血清抗体靶点，然后对其进行了寄生虫基因本体生物学过程和细胞成分的表征，结果显示与免疫逃避、发病机制以及在宿主细胞和寄生虫表面表达相关的类别有显著富集。此外，我们计算了免疫原性蛋白质的年龄拟合年度血清转化率，并对比了两个采样点这些抗原的年龄依赖性抗体获得情况。我们观察到，在两个地点都有从幼年就产生稳定抗体反应的高免疫原性抗原，以及需要反复接触才能产生稳定反应且在不同地点产生不同血清转化率的低免疫原性蛋白质。我们建议，高免疫原性和低免疫原性蛋白质的组合可用于血清学调查，以检测疟疾传播水平的差异，区分不稳定和稳定传播的地点。
