SAFE VACCINE STRAIN OF LISTERIA MONOCYTOGENES FOR HIV

描述：一种能够针对类HIV蛋白的疫苗 I限制的抗原识别途径可能是一种强大的 艾滋病毒感染的预防性和可能的治疗剂。抗原 由单核细胞增生性李斯特菌分泌，是一种革兰氏阳性细菌，可以 生长在巨噬细胞和邻近细胞的细胞质内，将具有 直接进入MHC-I类途径获得细胞毒性T细胞。上一首 研究证实，重组李斯特菌具有 表达外源抗原，可用于成功保护小鼠 抗感染和肿瘤细胞挑战。然而，由L. 单核细胞增多症，虽然罕见，并由抗生素控制，但可导致 严重疾病，尤指免疫功能低下或怀孕的病人。 出于这些原因，有人建议进行实验，以开发一种超 单增李斯特氏菌减毒株作为HIV/SIV疫苗载体的研究。在……里面 初步研究人员已分离到一株L. 不能合成氨基酸D-丙氨酸的单核细胞增多症 是合成细胞壁所必需的。使用这种超级- 减毒的单核细胞增多性乳杆菌将为以下工作奠定基础 实验目标： 具体目标1：选育一株超弱毒力菌株。 表达HIV/SIV蛋白的单核细胞增多症。特定的AIM2：评估 减毒株传递HIV/SIV DNA疫苗的能力。 特异性目标3：优化小鼠细胞免疫应答 对减毒株表达或递送的HIV/SIV抗原。 具体目标4：检查抗原呈递的人体模型： 获得受感染的PBMC扩大患者HIV-1特异性的能力 CTL。

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.