CELLULAR IMMUNE RESPONSES TO SUBUNIT IMMUNODEFICIENCY VIRUS VACCINES

亚单位免疫缺陷病毒疫苗的细胞免疫反应

• 批准号: 6299486
• 负责人: PHILIP D GREENBERG
• 金额: $ 34.34万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-01-01 至 2000-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6299486
• 关键词: AIDS vaccines; CD4 molecule; CD8 molecule; Macaca nemestrina; T lymphocyte; active immunization; cell mediated lymphocytolysis test; cellular immunity; density gradient ultracentrifugation; human immunodeficiency virus 1; laboratory mouse; leukocyte activation /transformation; live vaccine; molecular cloning; nonhuman therapy evaluation; recombinant virus; simian immunodeficiency virus; vector vaccine; virus antigen

Advances in the development of a vaccine for HIV have been substantial. New vaccine vectors to deliver viral immunogens have been designed, vaccine preparations with enhanced immunogenicity have been produced based on a better understanding of the mechanisms of in vivo processing of antigens, new non-human primate models for HIV infection have been developed, and protective immunity in vaccinated non-human primates has been demonstrated under defined challenge conditions. Although many immunologic effector mechanisms with activity against HIV have been identified, the nature of the host immune responses necessary and sufficient for mediating protection have not been precisely defined. Characterizing such protective responses is essential to provide direction and establish immunologic goals for candidate vaccines. Studies are proposed in this project to continue our efforts to evaluate the role of specific components of vaccine-induced CD4+ and CD8+ T cell responses in protective immunity, determine the immunologic and virologic reasons why potentially protective T cell responses successfully or unsuccessfully resolve a viral challenge, and examine methods to improve the efficiency of T cell activation during vaccination. The studies will be performed in a non-human primate model with SHIV, a chimeric virus comprised of elements of HIV-1 and SIV, as the challenge virus. The specific aims are to: 1. evaluate the function, specificity, magnitude, and durability of T cell responses elicited by candidate vaccines; 2. correlate the T cell responses elicited by vaccines with the outcome of challenge with SHIV; 3. analyze the immunologic basis for failure of protection in vaccinated hosts; 4. evaluate the importance of CD4+ and CD8+ T cell subsets in protection by using adoptive T cell transfer to selectively enhance individual responses; and 5. examine new strategies designed to augment T cell responses elicited by candidate vaccines.

开发艾滋病毒疫苗的进展是很大的。 已经设计了新的疫苗向量来传递病毒免疫原子， 已经产生了具有增强免疫原性的疫苗制剂 基于对体内处理机制的更好理解 在抗原中，新的非人类灵长类动物模型已成为HIV感染 发达的和保护性的非人类灵长类动物的保护性免疫具有 在定义的挑战条件下被证明。 虽然很多 具有针对HIV活性的免疫效应器机制已 确定，宿主免疫反应的性质必要的， 足以进行介导保护尚未精确定义。 表征这种保护性反应对于提供 方向并建立候选疫苗的免疫目标。 在该项目中提出了研究，以继续我们的评估 疫苗诱导的CD4+和CD8+ T细胞的特定成分的作用 保护性免疫的反应，确定免疫学和 病毒学的原因为什么潜在的保护性T细胞反应 成功或未成功解决病毒挑战，并检查 提高T细胞激活效率的方法 疫苗接种。 研究将在非人类灵长类动物模型中进行 与Shiv一起，由HIV-1和SIV元素组成的嵌合病毒，如 挑战病毒。 具体目的是： 1。评估t的功能，特异性，幅度和耐用性 候选疫苗引起的细胞反应； 2。将疫苗引起的T细胞反应与结果相关联 Shiv的挑战； 3。分析接种疫苗的保护失败的免疫学基础 主持人； 4。评估CD4+和CD8+ T细胞子集的重要性 通过使用养子T细胞转移来选择性增强个体 回应；和 5。检查旨在增强T细胞响应的新策略 由候选疫苗。