ANTIGENIC ANALYSIS OF SEXUAL STAGES OF MALARIA PARASITES

四种潜在的靶抗原（Pfs 25/Pgs 25、Pfs 40、Pfs 230和Pgs 28） 我们的实验室已经克隆了阻断传播的抗体， 第五种（几丁质酶）已被鉴定。 在四种靶抗原中 已经克隆的，都已经在一个或多个重组体中表达 表达系统，但只有重组Pfs 25诱导传输- 阻断实验动物体内的抗体。 我们的近期目标是：（1） 在人类中测试Pfs 25亚基的安全性、免疫原性和功效 疫苗和设计一种测试这种传播效力的方法- 2）确定疫苗的作用，如果有的话， 钙结合Pfs 40在性发育中的作用，并确定Pfs 40 是传播阻断抗体的靶点; 3）鉴定和表达 作为重组蛋白，Pfs 230中的B细胞表位负责 我们的抗Pfs 230单克隆抗体的传递阻断活性; 4） 从恶性疟原虫中分离编码类似于 P.鸡Pgs 28; 5）测定几丁质酶抗体是否完全 阻断传播，如果是这样，分离并表达编码这个的基因， 动合子酶;和6）分离与这些类似的基因（如果它们存在） 其他人类疟疾寄生虫的五种蛋白质 我们更长期的 目标包括鉴定有性阶段寄生虫上的新靶抗原， 并确定受精的分子机制， 疟疾寄生虫

Four potential target antigens (Pfs25/Pgs25, Pfs40, Pfs230, and Pgs28) of transmission-blocking antibodies have now been cloned in our laboratory, and a fifth (chitinase) has been identified. Of the four target antigens that have been cloned, all have been expressed in one or more recombinant expression systems, but only recombinant Pfs25 has induced transmission- blocking antibodies in laboratory animals. Our immediate goals are to 1) test in humans the safety, immunogenicity, and efficacy of a Pfs25 subunit vaccine and design a means of testing the efficacy of such a transmission- blocking vaccine in the field; 2) 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; 3) identify and express as recombinant protein the B-cell epitopes in Pfs230 responsible for the transmission-blocking activity of our monoclonal antibodies to Pfs230; 4) isolate the gene from P. falciparum encoding the protein analogous to the P. gallinaceum Pgs28; 5) determine if antibodies to chitinase completely block transmission, and if so, isolate and express the gene encoding this ookinete enzyme; and 6) isolate analogous genes (if they exist) to these five proteins from the other human malaria parasites. 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.