CELLULAR IMMUNE RESPONSES TO SUBUNIT IMMUNODEFICIENCY VIRUS VACCINES

艾滋病毒疫苗的开发取得了实质性进展。 新的疫苗载体已经被设计出来，可以传递病毒免疫原， 具有增强免疫原性的疫苗制剂已经生产出来 基于对体内加工机制的更好理解 在抗原方面，新的非人类灵长类艾滋病毒感染模型已经被 在接种了疫苗的非人灵长类动物中产生了保护性免疫 已在定义的挑战条件下演示。虽然很多人 具有抗HIV活性的免疫效应机制一直是 所需的宿主免疫反应的性质以及 对调解保护的足够程度还没有得到准确的定义。 确定这种保护性反应的特征对于提供 指导和建立候选疫苗的免疫学目标。 在这个项目中提出了研究建议，以继续努力评估 疫苗诱导的CD4+和CD8+T细胞特异性成分的作用 保护性免疫中的反应，确定免疫学和 潜在保护性T细胞反应的病毒学原因 成功或失败地解决病毒挑战，并检查 提高T细胞活化效率的方法 接种疫苗。这些研究将在非人类灵长类动物模型中进行 在SHIV中，一种由HIV-1和SIV组成的嵌合病毒，AS 挑战病毒。具体目标是： 1.评估T细胞的功能、特异性、大小和持久性 候选疫苗引起的细胞反应； 2.将疫苗引发的T细胞反应与结果相关联 对希夫的挑战； 3.分析疫苗免疫失败的免疫学基础。 东道主； 4.评估CD4+和CD8+T细胞亚群在保护中的重要性 通过使用过继T细胞转移选择性增强个体 答复；以及 5.研究旨在增强T细胞反应的新策略 通过候选疫苗。

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.