SAFE VACCINE STRAIN OF LISTERIA MONOCYTOGENES FOR HIV

艾滋病毒单核细胞增生李斯特氏菌的安全疫苗株

• 批准号: 2649221
• 负责人: Fred Robert Frankel
• 金额: $ 31.9万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-03-01 至 2001-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2649221
• 关键词: AIDS vaccines; Listeria; MHC class I antigen; antigen presentation; attenuated microorganism; cytotoxic T lymphocyte; human immunodeficiency virus 1; laboratory mouse; simian immunodeficiency virus; tissue /cell culture; transfection; vaccine development; vector vaccine; virus antigen

DESCRIPTION: A vaccine that is able to target HIV proteins to the class I restricted pathway of antigen recognition could be a powerful prophylactic and possibly therapeutic agent for HIV infections. Antigens secreted by Listeria monocytogenes, a gram-positive bacterium that can grow within the cytoplasm of macrophages and adjoining cells, will have direct access to the MHC class I pathway to cytotoxic T cells. Previous studies have established that recombinant Listeria have the capacity to express foreign antigens and can be used to successfully protect mice against infection and tumor cell challenge. However, infection by L. monocytogenes, while rare and controlled by antibiotics, can cause serious illness, particularly in immune suppressed or pregnant patients. For these reasons, experiments are proposed to develop a hyper- attenuated strain of L. monocytogenes as an HIV/SIV vaccine vector. In preliminary studies the investigator has isolated a strain of L. monocytogenes that is unable to synthesize D-alanine, an amino acid required for the synthesis of the cell wall. The use of this hyper- attenuated L. monocytogenes will form the foundation for the following experimental aims: Specific Aim 1: To develop a hyper-attenuated strain of L. monocytogenes expressing HIV/SIV proteins. Specific Aim2: To evaluate the ability of the attenuated strains to deliver HIV/SIV DNA vaccines. Specific Aim 3: To optimize the cell mediated immune response in mice to HIV/SIV antigens expressed or delivered by the attenuated strains. Specific Aim 4: To examine a human model of antigen presentation: to access the ability of infected PBMCs to expand patient HIV-1-specific CTLs.

描述：能够将HIV蛋白靶向类的疫苗 我限制了抗原识别的途径可能是一个有力的 预防性和可能用于HIV感染的治疗剂。抗原 由单核细胞增生李斯特菌分泌，一种革兰氏阳性细菌，可以 在巨噬细胞和相邻细胞的细胞质内生长 直接访问MHC I类通往细胞毒性T细胞的途径。 以前的 研究已经确定重组李斯特菌具有 表达外国抗原，可用于成功保护小鼠 反对感染和肿瘤细胞挑战。 但是，L。感染。 单核细胞增生剂虽然罕见且受抗生素控制，但可能会导致 严重疾病，特别是在免疫抑制或孕妇中。 由于这些原因，提出了实验以发展高度 单核细胞增生李斯特菌的减毒菌株作为HIV/SIV疫苗载体。 在 初步研究研究者已经分离了L。 无法合成D-丙氨酸（氨基酸）的单核细胞增生。 合成细胞壁所必需的。 使用这个超级 衰减的单核细胞增生李斯特氏菌将为以下 实验目的： 特定目标1：开发L. 表达HIV/SIV蛋白的单核细胞增生。 特定目标2：评估 减毒菌株输送HIV/SIV DNA疫苗的能力。 特定目标3：优化小鼠细胞介导的免疫反应 致衰减菌株表达或递送的HIV/SIV抗原。 特定目的4：检查人类抗原表现模型： 访问感染PBMC扩大患者HIV-1特异性的能力 CTL。