Immunological Cross-Reactivity between Malaria Vaccine Target Antigen P48/45 in Plasmodium vivax and P. falciparum and Cross-Boosting of Immune Responses.
Immunological Cross-Reactivity between Malaria Vaccine Target Antigen P48/45 in Plasmodium vivax and P. falciparum and Cross-Boosting of Immune Responses.
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DOI：
10.1371/journal.pone.0158212
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Kumar N
中科院分区：
文献类型：
--
作者：
Cao Y;Bansal GP;Merino K;Kumar N
一般来说，疟疾免疫被认为是物种特异性的，间日疟原虫和恶性疟原虫之间几乎没有已知的交叉反应性，这两种疟原虫都导致了90%的人类疟疾，并在许多国家共同流行。因此，我们认为可能需要针对不同种类疟原虫的物种特异性免疫。Pfs48/45和Pvs48/45是疟疾寄生虫性阶段的明确目标，目前正在开发阻断传播的疫苗。它们的序列比较显示在DNA和蛋白质水平上分别有61%和55%的同源性，这提高了这两个目标抗原可能共享交叉反应表位的可能性。在成功表达重组Pfs48/45和Pvs48/45蛋白后，我们假设这些蛋白不仅会表现出免疫交叉反应性，还会交叉促进免疫反应。以CFA、Montanide ISA-51和明本作为佐剂，用纯化的重组蛋白免疫小鼠，并通过ELISA、Western blotting和间接固定和活IFA分析血清，以验证这一假设。我们的研究表明，pvs48 /45免疫血清对Pfs48/45全长蛋白表现出较强的交叉反应性，且这种交叉反应性主要发生在Pfs48/45的氨基端和羧基端亚片段上。在交叉增强实验中，Pfs48/45和Pvs48/45抗原在小鼠免疫研究中能够相互交叉增强。此外，我们还注意到佐剂对观察到的交叉反应性的总体大小的影响。这些研究可能对两种疟疾寄生虫的免疫靶向传播具有重要意义。
In general, malaria immunity has been suggested to be species specific with very little, if any, known cross-reactivity between Plasmodium vivax and P. falciparum, both of which are responsible for >90% of human malaria, and co-endemic in many countries. It is therefore believed that species-specific immunity may be needed to target different species of Plasmodium. Pfs48/45 and Pvs48/45 are well established targets in the sexual stages of the malaria parasites, and are being pursued for the development of transmission blocking vaccines. Comparison of their sequences reveals 61% and 55% identity at the DNA and protein level, respectively raising the possibility that these two target antigens might share cross-reacting epitopes. Having succeeded in expressing recombinant Pfs48/45 and Pvs48/45 proteins, we hypothesized that these proteins will not only exhibit immunological cross–reactivity but also cross-boost immune responses. Mice were immunized with purified recombinant proteins using CFA, Montanide ISA-51 and alum as adjuvants, and the sera were analyzed by ELISA, Western blotting and indirect fixed and live IFA to address the hypothesis. Our studies revealed that Pvs48/45-immune sera showed strong cross-reactivity to full length Pfs48/45 protein, and the majority of this cross reactivity was in the amino-terminal and carboxyl-terminal sub-fragments of Pfs48/45. In cross-boosting experiments Pfs48/45 and Pvs48/45 antigens were able to cross-boost each other in mouse immunization studies. Additionally we also noticed an effect of adjuvants in the overall magnitude of observed cross-reactivity. These studies may have significant implications for immunity targeting transmission of both the species of malaria parasites.