Safety and Efficacy of SHIV Vaccine in Macaques

SHIV 疫苗在猕猴中的安全性和有效性

• 批准号: 6622528
• 负责人: OPENDRA NARAYAN
• 金额: $ 71.27万
• 依托单位: UNIVERSITY OF KANSAS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-06-15 至 2006-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6622528
• 关键词: AIDS vaccines; Macaca; active immunization; antiantibody; antigen antibody reaction; antiviral agents; blood cell count; cell mediated lymphocytolysis test; cell sorting; cellular immunity; cytotoxic T lymphocyte; drug screening /evaluation; enzyme linked immunosorbent assay; flow cytometry; immunologic memory; immunosuppression; immunotherapy; longitudinal animal study; lymph nodes; nonhuman therapy evaluation; nucleic acid purification; polymerase chain reaction; simian immunodeficiency virus; vaccine evaluation; virus DNA; virus cytopathogenic effect; virus replication

DESCRIPTION: (Provided by Applicant) This is an application to continue longitudinal studies in macaques that have been used to explore mechanisms of safety of a SHIV vaccine, and the remarkable effectiveness of this vaccine not only in conferring long term protection against disease caused by pathogenic SIV and SHIVs, but also elimination of these pathogens given as challenge. Earlier studies established that the vaccine is safe for at least 4 years after inoculation into newborns and after serial passage in young macaques. Studies on efficacy showed that following transient replication, virus could not be re-isolated from the animals but viral DNA persisted for more than 4 years in lymphoid tissues. Immunized animals challenged with pathogenic viruses between 7 and 18 months later became infected but replication of these agents was dramatically curtailed, and in many animals, both the challenge viruses and their DNA became progressively undetectable during three years of post-challenge study. Infectious DNA of the vaccine virus is effective in causing the immunizing infection, and because it induces immune responses to some HIV proteins, it has been proposed to the FDA as a therapeutic vaccine for HIV-infected persons. Data from studies proposed in this application will be used as preclinical support for an IND application to the FDA. New proposed studies will address the following devil's advocate hypothesis: 1. Challenge viruses that are thought to have been eliminated are still present in lymphoid tissues and can be induced by treatment of the challenged animals with anti-CD8+T cell mAb. 2. The vaccine-induced long-term efficacy that correlates with persistence of memory antiviral CD8+T cells, is maintained by antigen provided by persistently-replicating vaccine virus in lymphoid tissues. This will be tested in studies in which some immunized animals will be treated with anti CD8+T cell mAbs to induce the virus. Others will be treated with PMPA to suppress putative virus replication so that immune responses will decay in the absence of antigen. Further, new animals will be inoculated with lymph node cells from virus-negative, immune animals and tested for infection. 3. Pathogenicity of the vaccine virus could be demonstrated by further serial passage of the virus in new animals, and by injection of the agent into macaques that are immunosuppressed by treatment with anti-CD8+T cell mAbs.

描述：（由申请人提供）这是一个继续申请 在猕猴中进行的纵向研究， SHIV疫苗的安全性，以及这种疫苗的显著效果， 只有在提供长期的保护，防止疾病引起的致病性 SIV和SHIV，但也消除这些病原体作为挑战。 早期的研究表明，疫苗在接种后至少4年内是安全的。 接种到新生猴中和在年轻猕猴中连续传代后。研究 结果表明，在短暂复制后，病毒不能被 从动物身上重新分离出来，但病毒DNA持续了4年多， 淋巴组织用致病性病毒攻毒的免疫动物 7和18个月后被感染，但这些因子的复制是 在许多动物中，挑战病毒和 他们的DNA在三年的时间里逐渐无法检测到， 攻毒后研究。 疫苗病毒的感染性DNA有效地引起免疫 感染，并且因为它诱导对某些HIV蛋白质的免疫反应， 作为HIV感染者的治疗性疫苗向FDA提出。 本申请中拟定的研究数据将用作临床前研究数据。 支持向FDA提交IND申请。 新提出的研究将解决以下魔鬼代言人假设：1。 被认为已经被消灭的挑战病毒仍然存在于 并且可以通过用以下物质处理激发的动物来诱导 抗CD 8 +T细胞mAb。2.疫苗诱导的长期疗效与 与持久的记忆抗病毒的CD 8 +T细胞，是维持抗原 由淋巴组织中持续复制的疫苗病毒提供。这 将在研究中进行测试，其中一些免疫动物将用 抗CD 8 +T细胞mAb诱导病毒。其他人将接受PMPA治疗， 抑制假定的病毒复制，使免疫反应将衰减， 没有抗原。此外，新动物将接种淋巴结 来自病毒阴性免疫动物的细胞并测试感染。3. 疫苗病毒的致病性可以通过进一步的系列试验来证明。 病毒在新动物中的传代，以及通过将试剂注射到 通过用抗-CD 8 +T细胞mAb处理而免疫抑制的猕猴。