CIRCUMSPOROZOITE BASED MULTIPLE ANTIGEN PEPTIDES AS MALARIA VACCINE

在过去的几年里，司法部的调查人员 纽约大学医学院的医学和分子寄生虫学 已经探索了多种抗原肽(MAP)的使用 作为疟疾疫苗的基础。这项工作的重点是 来自环孢子虫蛋白(CSP)的多肽；实验 基于人类疟疾寄生虫CSP的免疫原已经被 研究免疫原性，而啮齿动物疟疾寄生虫同源 系统已经实现了免疫原性和有效性的确定。 从CSP的中心重复区域衍生的序列具有 提供给地图的B表位部分，而T表位来自 CSP的几个部分已经使用。地图已经制作好了 经ELISA效价测定，显示出良好的免疫原性。 抗免疫原和IFA效价抗整个子孢子。 高免疫原性地图已被证明对啮齿类动物具有高度保护作用 疟疾系统。特别是一张恶性疟原虫的地图， 命名为(T1B)4已被证明具有高度的免疫原性。什么时候 用明矾作为佐剂，该MAP具有高度的免疫原性 应答小鼠品系，导致抗体滴度顺序为 比免疫方案中看到的更大的是 一种用于诱导对疟疾的保护的标准 包括人类恶性疟原虫感染在内的寄主寄生虫系统。 根据这一信息，决定使用这张地图 作为疫苗的基础，并将在人体上进行测试。一块试验田 已经由一家商业实验室合成，能够 根据GMP和GMP批次进行的生产正在计划中，以供制定 加明矾。用高效液相色谱(HPLC)、十二烷基硫酸钠-聚丙烯酰胺凝胶(SDS-PAGE)、凝胶 过滤、氨基酸分析、质谱学、反应性 参考单抗，以及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.