CIRCUMSPOROZOITE BASED MULTIPLE ANTIGEN PEPTIDES AS MALARIA VACCINE

在过去的几年里， 纽约大学学院医学与分子寄生虫学 已经探索了使用多抗原肽（MAP） 作为疟疾疫苗的基础。 工作重点是 环孢子体蛋白（CSP）衍生肽;实验性 基于人类疟疾寄生虫CSP的免疫原已经被 研究了免疫原性，而啮齿类疟原虫同源物 系统已经能够进行免疫原性和功效测定。 衍生自CSP的中心重复区的序列具有 提供给MAP的B表位部分，而来自MAP的T表位 已经使用了CSP的几个部分。 已制作地图 通过ELISA滴度测定其显示出优异的免疫原性 针对免疫原和针对整个子孢子的IFA滴度。 高免疫原性MAP已被证明在啮齿动物中具有高度保护性 疟疾系统。 一种恶性疟原虫MAP， 命名为（T1 B）4的抗体已被证明是高度免疫原性的。 当 与明矾作为佐剂一起施用，这种MAP在免疫原性方面是高度免疫原性的。 应答小鼠品系，导致抗体滴度为 比免疫方案中看到的更大的幅度是 用于在各种品种中诱导抗疟疾保护的标准 包括人类恶性疟原虫感染在内的宿主寄生虫系统。 根据这一信息，决定使用MAP 作为疫苗的基础，并将在人类身上进行测试。 一个试点地段 的MAP已经由商业实验室合成， 根据GMP生产，正在计划GMP批次用于配制 用明矾 用HPLC、SDS-PAGE、凝胶电泳、紫外分光光度计、紫外分光光度计等方法对MAP进行了表征 过滤，氨基酸分析，质谱，反应性 参考单克隆抗体，免疫原性和人体试验， 计划在不久的将来。

Over the past several years, investigators in the Department of Medical and Molecular Parasitology at the New York University School of Medicine have explored the use of multiple antigen peptides (MAPs) as the basis for vaccines against malaria. The work has focused on peptides derived from the circumsporozite protein (CSP); experimental immunogens based on the CSP of human malaria parasites have been studied for immunogenicity, while rodent malaria parasite homolog systems have enabled both immunogenicity and efficacy determinations. Sequences derived from the central repeat region of the CSP have provided to B epitopes portion of the MAPs, whereas T epitopes from several portions of the CSP have been used. MAPs have been produced which exhibit excellent immunogenicity as determined by ELISA titers against the immunogens and IFA titers against whole sporozoites. Highly immunogenic MAPs have proven to be highly protective in rodent malaria systems. One Plasmodium falcip arum MAP in particular, designated (T1B)4 has proven to be highly immunogenic. When administered with alum as adjuvant, this MAP is highly immunogenic in responder mouse strains, resulting in antibody titers orders of magnitude greater than those seen in immunization regimen is the standard used for induction of protection against malaria in a variety of host parasite systems including P.falcimarum infections in humans. Based on this information, it was decided that the MAP would be used as the basis of a vaccine and would be tested in humans. A pilot lot of MAP has been synthesized by a commercial laboratory capable of production under GMP and a GMP lot is being planned for formulation with alum. The MAP has been characterized by HPLC, SDS-PAGE, gel filtration, amino acid analysis, mass spectrometry, reactivity with reference monoclonal antibody, and immunogenicity and human trials are planned for the near future.