Rajesh Vidya, Singamsetti Vijay Kumar, Vidya S, Gowrishankar M, Elamaran M, Tripathi Jyotsna, Radhika N B, Kochar Dhanpat, Ranjan Akash, Roy S K, Das Ashis
Biological Sciences Group, Birla Institute of Technology and Science, Centre for Biotechnology, Pilani 333031, Rajasthan, India.
Exp Parasitol. 2008 May;119(1):144-51. doi: 10.1016/j.exppara.2008.01.019. Epub 2008 Feb 9.
A number of stage-specific antigens have been characterized for vaccine development against Plasmodium falciparum malaria. This study presents a comprehensive analysis of the sequence polymorphism in Plasmodium falciparum apical membrane antigen-1 (PfAMA-1) in population samples from the eastern and western parts of India. This is the first study of its kind for the nearly full length PfAMA-1 gene from these regions in India. Our observations confirmed that sequence diversity of PfAMA-1 confines only to point mutations and shows 4-8% variation as compared to the prototypes. As opposed to the previous studies on PfAMA-1, our study revealed a greater degree of polymorphism in the Domain II region of PfAMA-1 protein, though signature for diversifying selection is seen throughout the gene. Our present investigation also indicates a very high degree of variation in the reported T- and B-cell epitopes of PfAMA-1. Few noteworthy and unique observations made in this study are the substitution of Cysteine residues responsible for the disulfide bond structure of the protein and the presence of premature termination after 595 amino acids in 3 of the 13 isolates under consideration. These crucial findings add new perspectives to the future of AMA-1 research and could have major implications in establishing AMA-1 as a vaccine candidate.
已经鉴定出多种阶段特异性抗原，用于开发抗恶性疟原虫疟疾的疫苗。本研究对来自印度东部和西部人群样本中的恶性疟原虫顶膜抗原-1（PfAMA-1）的序列多态性进行了全面分析。这是首次对来自印度这些地区的几乎全长的PfAMA-1基因进行此类研究。我们的观察结果证实，PfAMA-1的序列多样性仅局限于点突变，与原型相比显示出4%-8%的变异。与先前关于PfAMA-1的研究不同，我们的研究揭示了PfAMA-1蛋白结构域II区域中更高程度的多态性，尽管在整个基因中都能看到多样化选择的特征。我们目前的研究还表明，PfAMA-1报道的T细胞和B细胞表位存在非常高的变异。本研究中一些值得注意和独特的观察结果是，负责蛋白质二硫键结构的半胱氨酸残基发生了取代，并且在所研究的13个分离株中有3个在595个氨基酸后出现了提前终止。这些关键发现为AMA-1研究的未来增添了新的视角，并可能对将AMA-1确立为候选疫苗产生重大影响。
