ANTIGENIC ANALYSIS OF SEXUAL STAGES OF MALARIA PARASITES

今年，非洲将有100到300万儿童死于疟疾。 为了控制疟疾，目前正在开发几种疫苗方法，其中一种 它是针对性阶段的(也就是传播阻断 疫苗)。编码四种潜在传播阻断靶点的基因 传播阻断抗原(Pfs25、Pfs28、Pfs40和Pfs230) 我们实验室现在已经克隆了抗体，还有五分之一，一种 一种是寄生虫产生的几丁质酶，第六种是蚊子产生的蛋白酶， 已经被确认了。在已经克隆的四种靶抗原中， 它们都在一个或多个重组表达系统中表达， 但只有rPfs25和rPfs28诱导了传播阻断抗体 在实验动物身上。我们目前的目标是在人类身上测试 RPfs25亚单位疫苗的安全性、免疫原性和有效性 设计一种测试这种传输阻断效果的方法 现场疫苗，2)提高诱导的rPfs28的表达 阻断抗体并检测rPfs25和rPfs28的各种组合 在一种适合人类使用的鸡尾酒疫苗中确定 联合使用可导致更长时间或更高滴度的传播阻断 抗体，3)确定钙结合Pfs40的作用(如果有的话) 在性发育中发挥作用，并确定Pfs40是否是 传播阻断抗体，4)促进rPfs230的表达 所以它诱导的抗体相当于传播的抗体- 阻断Pfs230的单抗，5)分离和表达编码Pfs230的基因 寄生虫产生的几丁质酶和蚊子产生的蛋白酶，以及6) 分离出与这五种寄生虫蛋白相似的基因，如果它们存在的话， 来自间日疟原虫。我们更长期的目标包括确定新的目标 有性期寄生虫的抗原及其分子机制的确定 参与疟疾寄生虫的受精。

One to three million children in Africa will die of malaria this year. To control malaria, several vaccine approaches are being developed, one of which is against the sexual stages (aka a transmission-blocking vaccine). The genes encoding four potential transmission-blocking target antigens (Pfs25, Pfs28, Pfs40, and Pfs230) of transmission-blocking antibodies have now been cloned in our laboratory, and a fifth, a parasite-produced chitinase, and a sixth, a mosquito-produced protease, have been identified. Of the four target antigens that have been cloned, all have been expressed in one or more recombinant expression systems, but only rPfs25 and rPfs28 have induced transmission-blocking antibodies in laboratory animals. Our immediate goals are to 1) test in humans the safety, immunogenicity, and efficacy of a rPfs25 subunit vaccine and design a means of testing the efficacy of such a transmission-blocking vaccine in the field, 2) improve expression of the rPfs28 that induces blocking antibodies and test various combinations of rPfs25 and rPfs28 in a cocktail vaccine suitable for use in humans to determine if the combination elicits longer lasting or higher titer transmission-blocking antibodies, 3) determine the role, if any, that the calcium-binding Pfs40 plays in sexual development and ascertain if Pfs40 is a target of transmission-blocking antibodies, 4) improve the expression of rPfs230 so that it induces antibodies equivalent to those of transmission- blocking mAbs to Pfs230, 5) isolate and express the genes encoding the parasite-produced chitinase and mosquito-produced proteases, and 6) isolate analogous genes to the five parasite proteins, if they exist, from P. vivax. Our more long-term goals include identifying new target antigens on sexual stage parasites, and defining the molecular mechanisms involved in fertilization of malarial parasites.