IMMUNIZATION AND CHALLENGE OF MACAQUES WITH SIV

猕猴 SIV 的免疫接种和攻击

• 批准号: 3746868
• 负责人: PATRICIA N FULTZ
• 金额: --
• 依托单位: FREE UNIVERSITY OF BRUSSELS-JETTE CAMPUS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3746868
• 关键词: AIDS; AIDS vaccines; Cercocebus; Macaca; active immunization; biological products; cell type; cellular immunity; drug delivery systems; gel electrophoresis; genetic manipulation; human immunodeficiency virus; humoral immunity; immunocytochemistry; in situ hybridization; nucleic acid probes; polymerase chain reaction; protein engineering; recombinant DNA; simian immunodeficiency virus; virulence; virus antigen; virus cytopathogenic effect; virus infection mechanism; virus morphology; virus protein

The simian immunodeficiency virus, SIV, is a lentivirus with many of the same properties as HIV, including cellular tropism, molecular heterogeneity, and induction of an AIDS-like disease in experimentally inoculated macaques. We propose to use the SIV- macaque system to test prototype vaccines for immunogenicity and protective and therapeutic efficacy. The primary goal of this project is to identify a vaccine that protects macaques from infection by SIV as a prototype after which a vaccine against HIV can be designed. Initially, to maximize the possibility for success and minimize the possibility that vaccine failure may be due to antigenic heterogeneity among SIV isolates or to variants in the vaccine challenge virus, the BK28 molecular clone of SIVmac will be used both as the source of vaccine antigens and infectious challenge virus. Proteins encoded by the SIVmac-BK28 env, gag, pol, and nef genes will be produced by recombinant DNA techniques and administered to macaques in the form of ISCOMs, Colloidomes, liposomes, or intact inactivated or non-infectious SIV virions. Humoral and cell-mediated immunity to SIV will be determined before and after intravenous challenge with either cell-free or cell- associated virus. Protection against homologous virus challenge will be assessed by failure to isolate or to detect virus by coculture and PCR techniques. We will also determine whether immunized macaques can be protected from challenge with a pathogenic heterologous strain of SIV (SIV/SMM, isolated from mangabey monkeys). To understand the pathogenesis of attenuated versus virulent SIV infection in macaques, the tissue tropism and lesions produced by molecularly cloned pathogenic strains will be established using immunocytochemical and.in situ hybridization analysis of tissues from animals infected with BK28 and a prototype pathogenic SIV. If protection against heterologous challenge with virulent SIV/SMM can not be demonstrated, experiments will be performed to determine whether immunization alters virus disease pathogenesis. Finally, we will evaluate the ability of vaccine administration to enhance SIV-specific immune responses or to alter progression to AIDS following immunization of macaques in various stages in the course of SIV infection. The proposed research will provide data pertinent to strategies for vaccination against HIV infection or disease.

猿猴免疫缺陷病毒（SIV）是一种慢病毒，具有许多特征 与 HIV 具有相同的特性，包括细胞向性， 分子异质性和艾滋病样疾病的诱导 实验性接种的猕猴。 我们建议使用 SIV- 猕猴系统测试原型疫苗的免疫原性和 保护和治疗功效。 此次活动的首要目标 该项目的目的是确定一种疫苗，可以保护猕猴免受 以 SIV 感染为原型，然后研制出抗 HIV 疫苗 可以设计。 最初，为了最大化可能性 并最大限度地减少疫苗失败的可能性 由于 SIV 分离株或变异体之间的抗原异质性 在疫苗攻击病毒中，SIVmac 的 BK28 分子克隆 将用作疫苗抗原和传染性抗原的来源 挑战病毒。 由 SIVmac-BK28 env、gag、 pol和nef基因将通过重组DNA技术产生 并以 ISCOM、Colloidomes 的形式给予猕猴， 脂质体，或完整的灭活或非感染性 SIV 病毒颗粒。 对 SIV 的体液和细胞介导的免疫将在之前确定 并在用无细胞或细胞-静脉注射攻击后 相关病毒。 抵御同源病毒挑战 将通过未能分离或检测病毒来评估 共培养和 PCR 技术。 我们还将确定是否 免疫后的猕猴可以通过以下方法免受攻击： SIV 致病性异源株（SIV/SMM，分离自 曼加贝猴）。 了解弱毒症的发病机制 与猕猴中的强毒 SIV 感染相比，组织向性和 分子克隆致病菌株产生的病变将 使用免疫细胞化学和原位杂交建立 对感染 BK28 的动物组织和原型进行分析 致病性SIV。 如果针对异源挑战的保护 无法证明 SIV/SMM 的毒性，将进行实验 确定免疫接种是否会改变病毒性疾病 发病。 最后，我们将评估疫苗的能力 施用以增强 SIV 特异性免疫反应或改变 猕猴在各种情况下免疫接种后进展为艾滋病 SIV 感染过程中的各个阶段。 拟议的研究将 提供与艾滋病毒疫苗接种策略相关的数据 感染或疾病。