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: 6163938
• 负责人: Fred Robert Frankel
• 金额: $ 32.11万
• 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 2002-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6163938
• 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：一种能够针对此类 HIV 蛋白的疫苗 我限制性抗原识别途径可能是一种强大的 HIV感染的预防剂和可能的治疗剂。抗原 由单核细胞增生李斯特氏菌分泌，这是一种革兰氏阳性细菌，可以 在巨噬细胞和邻近细胞的细胞质内生长，将具有 直接进入细胞毒性 T 细胞的 MHC I 类途径。 以前的 研究已证实重组李斯特菌有能力 表达外源抗原并可用于成功保护小鼠 对抗感染和肿瘤细胞的挑战。 然而，L感染。 单核细胞增多症虽然罕见且受抗生素控制，但可导致 严重疾病，特别是免疫抑制或怀孕的患者。 由于这些原因，建议进行实验来开发一种超 单增李斯特菌减毒株作为 HIV/SIV 疫苗载体。 在 初步研究中，研究者分离出一株 L. 无法合成 D-丙氨酸（一种氨基酸）的单核细胞增多症 细胞壁合成所需的。 使用这种超 减毒单核细胞增生李斯特氏菌将为以下方面奠定基础 实验目的： 具体目标 1：开发 L. 超减毒菌株。 表达 HIV/SIV 蛋白的单核细胞增多症。 具体目标2：评估 减毒株提供 HIV/SIV DNA 疫苗的能力。 具体目标 3：优化小鼠细胞介导的免疫反应 减毒株表达或递送的HIV/SIV抗原。 具体目标 4：检查人类抗原呈递模型： 获得受感染的 PBMC 扩大患者 HIV-1 特异性的能力 CTL。