ANTIGENIC ANALYSIS OF SEXUAL STAGES OF MALARIA PARASITES

今年非洲将有200多万儿童死于疟疾。到 为了控制疟疾，正在开发几种疫苗方法， 这是针对性阶段（又名传播阻断疫苗）。 编码四种潜在的传播阻断靶抗原的基因 （Pfs 25、Pfs 28、Pfs 40和Pfs 230）的传播阻断抗体 现在已经在我们的实验室里被克隆了，第五个，一个寄生虫产生的， 几丁质酶和第六种蚊子产生的蛋白酶， 鉴定 在已经克隆的四种靶抗原中， 在一个或多个重组表达系统中表达。 rPfs25， rPfs 28和rPfs 230在小鼠中诱导了传播阻断抗体， 实验室动物 我们的近期目标是1）在人类身上测试 rPfs 25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 2）提高rPfs 28的表达， 封闭抗体，并测试rPfs 25和rPfs 28的各种组合 在适用于人类的鸡尾酒疫苗中， 联合使用可延长或提高传播阻断滴度 抗体，3）确定的作用，如果有的话，钙结合Pfs 40 在性发育中起作用，并确定Pfs40是否是 4）提高rPfs 230的表达 这样它就能诱导出与传染病相同的抗体 5）分离并表达编码Pfs 230的基因， 寄生虫产生的几丁质酶和蚊子产生的蛋白酶，和6） 分离出与这五种寄生虫蛋白质类似的基因，如果它们存在的话， 间日疟原虫 我们的长期目标包括确定新的目标 性阶段寄生虫的抗原，并确定分子机制 参与疟疾寄生虫的受精。

Over two 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. rPfs25, r Pfs28 and rPfs230 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.