Bailey Jeffrey A, Mvalo Tisungane, Aragam Nagesh, Weiser Matthew, Congdon Seth, Kamwendo Debbie, Martinson Francis, Hoffman Irving, Meshnick Steven R, Juliano Jonathan J
Division of Transfusion Medicine and Program in Bioinformatics and Integrative Biology, University of Massachusetts School of Medicine, Worcester, USA.
J Infect Dis. 2012 Aug 15;206(4):580-7. doi: 10.1093/infdis/jis329. Epub 2012 May 2.
The development of an effective malaria vaccine has been hampered by the genetic diversity of commonly used target antigens. This diversity has led to concerns about allele-specific immunity limiting the effectiveness of vaccines. Despite extensive genetic diversity of circumsporozoite protein (CS), the most successful malaria vaccine is RTS/S, a monovalent CS vaccine. By use of massively parallel pyrosequencing, we evaluated the diversity of CS haplotypes across the T-cell epitopes in parasites from Lilongwe, Malawi. We identified 57 unique parasite haplotypes from 100 participants. By use of ecological and molecular indexes of diversity, we saw no difference in the diversity of CS haplotypes between adults and children. We saw evidence of weak variant-specific selection within this region of CS, suggesting naturally acquired immunity does induce variant-specific selection on CS. Therefore, the impact of CS vaccines on variant frequencies with widespread implementation of vaccination requires further study.
常用靶抗原的基因多样性阻碍了有效疟疾疫苗的研发。这种多样性引发了人们对等位基因特异性免疫限制疫苗效力的担忧。尽管环子孢子蛋白（CS）具有广泛的基因多样性，但最成功的疟疾疫苗是RTS/S，一种单价CS疫苗。通过使用大规模平行焦磷酸测序技术，我们评估了来自马拉维利隆圭的寄生虫中跨T细胞表位的CS单倍型的多样性。我们从100名参与者中鉴定出57种独特的寄生虫单倍型。通过使用多样性的生态和分子指标，我们发现成人和儿童的CS单倍型多样性没有差异。我们发现CS这一区域内存在微弱的变异特异性选择的证据，表明自然获得性免疫确实会对CS产生变异特异性选择。因此，随着疫苗的广泛接种，CS疫苗对变异频率的影响需要进一步研究。
