Studies on mutation in virulence of Plasmodium falciparum

通过引进安全有效的疫苗，将克服目前疟疾控制受阻的局面。为促进疫苗研究付出了很大努力。一些候选的多肽疫苗目前正在进行第二阶段的测试。然而，疫苗的长效保护作用尚未达到。我们已经提出，利用减毒寄生虫进行活体疫苗的研究可能会打开一些前景，以产生持久的效果。本研究以伯氏疟原虫(P.berghei，NK65)及其弱毒衍生物(XAT)为研究对象，建立了一种啮齿动物模型。经Western blotting分析，发现29KD抗原分子在XAT中缺失。用O，Farrell双向电泳法对该分子进行纯化，并进行氨基酸序列分析。四十个戒酒协会。序列已经确定，现在正在搜索相应的cdna。另一方面，使用急性疟疾病例的血清，收集来自高流行区、中流行区和低流行区居民的血清，并将其作为多克隆抗体用于比较蛋白质印迹抗原分析。在急性疟疾中，47KD分子一直存在，治疗后分子消失。在这一品系上，作为恶性疟原虫毒力标记表位的抗原分子条带。目前正在研究中。产生了抗间日疟原虫的单抗，对间日疟原虫的反应性比间日疟原虫弱。)都进行了测试。P.F.和P.V.用几种抗P.F.本计划的最终目标是获得控制P.F.毒力的功能性抗原分子。用多克隆抗体和单抗寄生。

Present situation of hampered malaria control will be overcome by the introduction of safe and effective vaccine. Much efforts are paid for the promotion of vaccine research. Some candidate peptide vaccines are now being tested at phase II stage. However, long lasting protective effect of the vaccine are not yet achieved. We have proposed that studies on live type vaccine using attenuated parasites may open some prospects to produce long lasting effect. In the present study, a rodent model was studied using virulent P. berghei(NK65) and its attenuated derivative P. berghei(XAT). By western blotting technique, it was found that 29KD antigenic molecule was deficient in XAT. The molecule was purified by O,Farrell's two dimentional electrophoresis and subjected to sequence analysis of amino acids. Fourty a.a. sequence was determined and corresponding cDNA is now being searched for. On the other hand, using sera from acute malaria cases, sera from inhabitants in hyper, meso, and hypoendemic areas are collected and they were used as polyclonal antibodies in comparative western blot antigen analyses. In acute malaria, 47KD molecule was always remarked and the molecule disappeared after treatment. On this line, antigenic molecule bands which work as marker epitopes of the virulence of P. falciparum(P.f.) are now being studied. Monoclonal antibodies to P. f. were produced and the reactivities to P. vivax(P.v.)less virulent than P.f.) were tested. P.f. and P.v. were differentiated by some monoclonal antibodies to P.f. Eventual aim of the present programme is to get functional antigenic molecules which control virulence of P.f. parasite using polyclonal and monoclonal antibodies.