Protective immunity induced by live attenuated SIV

描述（由申请人提供）：尽管进行了深入研究，但对HIV感染的保护性免疫相关的免疫应答仍然知之甚少。减毒SIV株免疫已被证明是诱导非人灵长类动物保护的最有效手段之一，因此，在该模型中分析保护性免疫提供了一个理想的研究环境，以确定可能在介导保护中发挥作用的特定机制。在上一个资助期进行的工作提供了一个由减毒SIV诱导的免疫反应的阵列的详细描述，并提供了相关的证据，细胞和体液免疫反应的作用，防止感染致病性SIV菌株。 然而，越来越多的证据表明，该模型中的保护机制的鉴定可能是复杂的，可能代表免疫系统的多个臂的贡献，并且可能根据攻击模型和宿主基因型而变化。目前的建议的总体目标是进一步剖析细胞和体液免疫应答在介导由活减毒SIV株诱导的保护中的相对作用。具体目标包括：1.研究CD 8 + T细胞应答在介导SIVmac 239 delta 3疫苗接种猕猴的阴道攻击保护中的作用。2.研究细胞和体液免疫应答在介导β-免疫猕猴抗静脉内攻击保护中的相对作用。3.对用减毒SIV免疫的猕猴静脉内攻击后发生的早期病毒学和免疫学事件进行详细检查。4.检查δ 3疫苗接种的猕猴中CD 8 + T细胞应答的演变。

DESCRIPTION (provided by applicant): Despite intensive study, the immune responses associated with protective immunity against HIV infection remain poorly understood. Immunization with attenuated SIV strains has proven to be one of the most effective means to induce protection in nonhuman primates, and analysis of protective immunity in this model thus offers an ideal research setting in which to define specific mechanisms that may play a role in mediating protection. Work conducted in the previous funding period has provided a detailed description of the array of immune responses induced by attenuated SIV and provided correlative evidence for roles for both cellular and humoral immune responses in protecting against infection with pathogenic SIV strains. However, increasing evidence suggests that identification of the mechanisms of protection in this model is likely to be complex, is likely to represent the contributions of multiple arms of the immune system and may vary depending on the challenge model and host genotype. The overall goal of the current proposal is to further dissect the relative roles of cellular and humoral immune responses in mediating protection induced by live attenuated SIV strains. Specific aims include: 1. To examine the role of CD8+ T cell responses in mediating protection against vaginal challenge in SIVmac239delta3-vaccinated macaques. 2. To examine the relative contributions of cellular and humoral immune responses in mediating protection against intravenous challenge in (3-vaccinated macaques. 3. To carry out a detailed examination of early virologic and immunologic events occurring following intravenous challenge of macaques immunized with attenuated SIV. 4. To examine the evolution of CD8+ T cell responses in delta3-vaccinated macaques.