Mamillapalli Anitha, Sunil Sujatha, Diwan Suraksha S, Sharma Surya K, Tyagi Prajesh K, Adak Tridibes, Joshi Hema, Malhotra Pawan
Department of Parasitolgy, National Institute for Malaria Research, New Delhi, India.
Malar J. 2007 Jul 20;6:95. doi: 10.1186/1475-2875-6-95.
The C-terminal region of merozoite surface protein-1 (MSP-1) is one of the leading candidates for vaccination against the erythrocytic stages of malaria. However, a major concern in the development of MSP-1 based malaria vaccine is the polymorphism observed in different geographical Plasmodium falciparum isolates. To explore whether the sequence heterogeneity of PfMSP-1 leads to variation in naturally acquired anti-MSP-119 antibodies, the present study was undertaken to study PfMSP-119 sequence polymorphism in malaria-endemic villages in eastern India and also carried out a competition enzyme-linked immunosorbent assay using three PfMSP-119 variant forms.
The sequence variations in the C-terminal region of PfMSP-119 were determined in a malaria endemic region. Three PfMSP-119 variants were produced in Escherichia coli (PfMSP119QKNG-L, PfMSP119EKNG-L and PfMSP119ETSR-F) and an immunodepletion assay was carried out using the corresponding patients' sera.
Results revealed predominance of PfMAD20 allele among Indian field isolates. Seven PfMSP-119 variant forms were isolated in a singe geographical location. Three of PfMSP-119 variant forms when expressed in E. coli showed presence of cross-reaction as well as variant specific antibodies in malaria infected patient sera.
The present study demonstrates the existence of allele specific antibodies in P. falciparum-infected patient sera, however their role in protection requires further investigation. These results thereby, suggest the importance of a multi-allelic PfMSP-119 based vaccine for an effective malaria control.
裂殖子表面蛋白1(MSP-1)的C端区域是针对疟疾红细胞阶段进行疫苗接种的主要候选对象之一。然而,基于MSP-1的疟疾疫苗研发中的一个主要问题是在不同地理区域的恶性疟原虫分离株中观察到的多态性。为了探究恶性疟原虫MSP-1(PfMSP-1)的序列异质性是否导致自然获得的抗MSP-119抗体的变异,本研究对印度东部疟疾流行村庄的PfMSP-119序列多态性进行了研究,并使用三种PfMSP-119变体形式进行了竞争酶联免疫吸附试验。
在一个疟疾流行地区测定PfMSP-119 C端区域的序列变异。在大肠杆菌中产生了三种PfMSP-119变体(PfMSP119QKNG-L、PfMSP119EKNG-L和PfMSP119ETSR-F),并使用相应患者的血清进行了免疫耗竭试验。
结果显示PfMAD20等位基因在印度野外分离株中占主导地位。在单一地理位置分离出七种PfMSP-119变体形式。三种PfMSP-119变体形式在大肠杆菌中表达时,在疟疾感染患者血清中显示出交叉反应以及变体特异性抗体的存在。
本研究证明了恶性疟原虫感染患者血清中存在等位基因特异性抗体,然而它们在保护中的作用需要进一步研究。因此,这些结果表明基于多等位基因PfMSP-119的疫苗对于有效控制疟疾的重要性。