RECOMBINANT BCG MALARIA VACCINES

重组卡介苗疟疾疫苗

• 批准号: 6374196
• 负责人: WILLIAM Robert JACOBS
• 金额: $ 53.19万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-08-15 至 2003-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6374196
• 关键词: Aotus; Bacillus Calmette Guerin vaccine; Macaca mulatta; Mycobacterium bovis; Plasmodium; active immunization; bacterial antigens; laboratory mouse; malaria vaccines; recombinant proteins; vaccine development; vector vaccine

DESCRIPTION: (Adapted from Applicant's Abstract) Malaria is a major global health burden with annual incidences of 300 to 500 million cases and 1.5 to 2.7 million deaths per year. Development of a vaccine represents an essential goal for an effective control strategy. However, for a vaccine to have a significant impact it would need to be safe, easy to administer, effective in children and affordable in Africa. This laboratory has developed the systems to engineer BCG, the widely used tuberculosis vaccine into a recombinant BCG (rBCG) vaccine vector capable of expressing foreign antigens. Immunization with rBCG expressing viral, bacterial, or parasitic foreign antigens elicits antibody as well as CD4 and CD8 T cell responses to the foreign antigens in mice and monkeys. Recombinant BCG represents an attractive vaccine delivery system for Africa as BCG is a safe, inexpensive vaccine that is already administered to the majority of children at birth throughout Africa and the developing world. Previous studies have shown that immunization with the conserved antigen MSP-1 from a variety of Plasmodium species protects against challenge with the homologous Plasmodium species in mouse and monkey models. We have obtained expression of the conserved portion of the Plasmodium falciparum blood stage antigen MSP-1 on the surface of BCG. These expression constructs have been engineered into vectors that contain a gene that complements novel auxotrophic deletion mutations of BCG, to provide a selection system to maintain the plasmids when grown in mammalian hosts. We intend to express MSP-1 antigens of P. yoelii and P. knowlesi in these systems and then test the ability of all of the rBCG constructs to protect against malaria in mice, Aotus monkeys, and Rhesus monkeys. The immunization studies are designed to test the recombinant BCG's expressing MSP-1 for protection and their abilities to induce a priming immunization that can confer protection upon infection with the malarial parasites.

描述：（改编自申请人的摘要）疟疾是主要的全球 健康负担为300至5亿例，每年发生1.5至2.7 每年有百万人死亡。疫苗的开发代表了一个基本目标 有效的控制策略。但是，要使疫苗具有显着的 影响它需要安全，易于管理，对儿童有效，并且 在非洲负担得起。该实验室已经开发了工程的系统 BCG，广泛使用的结核病疫苗进入重组BCG（RBCG）疫苗 能够表达外国抗原的载体。 RBCG免疫 表达病毒，细菌或寄生的外抗原抗体作为抗体 以及小鼠中对外抗原的CD4和CD8 T细胞反应， 猴子。重组BCG代表了一个有吸引力的疫苗输送系统 非洲作为BCG是一种安全，廉价的疫苗 整个非洲和发展中国家出生的大多数儿童。 先前的研究表明，保守的抗原MSP-1免疫 来自各种疟原虫可以防止挑战 小鼠和猴子模型中的同源质质种。我们已经获得了 恶性疟原虫血液阶段的保守部分的表达 BCG表面上的抗原MSP-1。这些表达构造已经 设计成载体，该载体包含一个补充新型营养性的基因 删除BCG的突变，以提供选择系统以维护 在哺乳动物宿主中生长时质粒。我们打算表达MSP-1抗原 P. Yoelii和P. Knowlesi在这些系统中，然后测试所有的能力 加拿大皇家银行的构造可预防小鼠，aotus猴子和 恒河猴。免疫研究旨在测试重组 BCG表达MSP-1，以保护及其诱导启动的能力 可以在感染疟疾后提供保护的免疫接种 寄生虫。