HUMORAL AND CELLULAR IMMUNE RESPONSES TO HUMAN AND NONHUMAN PRIMATE RETROVIRUSES

重组腺病毒(Ad)-HIV的艾滋病疫苗途径 用包膜蛋白增强来启动已经被追求。黑猩猩 研究表明，对低剂量和高剂量的药物具有持久的保护作用 在不干预免疫接种的情况下应对艾滋病毒挑战。只有很少的数量 的免疫是诱导保护性免疫所必需的 能够中和初级分离株和实验室适应分离株的抗体。一个 细胞毒性T淋巴细胞在低剂量辐射防护中的作用 还提出了挑战。在经历了提振和第三次挑战之后 在3只受保护的黑猩猩中，有一只初级黑猩猩是非合胞体诱导的 隔离，一只动物受到完全保护，另一只动物表现出 与幼稚的控制相比，减少了病毒负担。这是第一次 对异源初级分离物的保护演示是 高度鼓舞和大力支持进一步发展这一 疫苗接种方法。用Ad宿主范围对恒河猴进行免疫 突变型SIV重组及SIV包膜蛋白启动子的构建 体液、细胞和粘膜免疫反应。阴道内SIV 挑战期间，病毒负担减少了10%到100% 感染期与对照猕猴相比。值得注意的是， 这两个系统都是使用仅基于病毒的疫苗实现的 信封。添加其他病毒成分应该会显著 提高保护性免疫力。对猕猴进行进一步的优质助推研究 使用分子减毒痘苗SIV重组体，有或没有 重组表达的细胞因子佐剂已显示出诱导 可溶性CD8+T细胞病毒抑制活性。挑战前的水平 这种活性与稳态血浆病毒rna水平相关。 静脉注射后SIV挑战。此外，挑战后的高水平 与非进步者状态相关，而低水平与 疾病进展迅速。这些发现为未来的疫苗设计提供了建议 应该包括诱导这种抑制活动。艾滋病标题： 腺病毒和减毒痘病毒载体在艾滋病疫苗开发中的应用

An AIDS vaccine approach combining adenovirus (Ad)-HIV recombinant priming with envelope protein boosting has been pursued. Chimpanzee studies demonstrated long-lasting protection against low- and high-dose HIV challenges without intervening immunizations. Only a minimal number of immunizations were necessary to elicit protective immunity along with antibodies capable of neutralizing primary and lab-adapted isolates. A role for cytotoxic T-lymphocytes in protection against low-dose challenge was also suggested. After boosting and a third re-challenge of the 3 protected chimpanzees with a non-syncytial- inducing primary isolate, one animal was completely protected and a second exhibited a reduced viral burden compared to the naive control. This first demonstration of protection against a heterologous primary isolate is highly encouraging and strongly supports further development of this vaccine approach. Priming of rhesus macaques with an Ad host range mutant-SIV recombinant and boosting with SIV envelope protein elicited humoral, cellular and mucosal immune responses. Upon intravaginal SIV challenge, the viral burden was reduced 10 to 100-fold during the acute infection period compared to control macaques. Notably, protection in both these systems was achieved using vaccines based only on the viral envelope. Addition of other viral components should significantly increase protective immunity. Further prime-boost studies in macaques using molecularly attenuated vaccinia SIV recombinants, with or without recombinant- expressed cytokine adjuvants, have shown induction of soluble CD8+ T-cell viral suppressive activity. Pre-challenge levels of this activity were correlated with steady-state plasma viral RNA levels post-intravenous SIV challenge. Moreover, high post-challenge levels correlated with non- progressor status while low levels correlated with rapid disease progression. These findings suggest future vaccine design should include induction of this suppressive activity. AIDS title: Adenovirus and Attenuated Poxvirus Vectors in AIDS Vaccine Development