HUMORAL AND CELLULAR IMMUNE RESPONSES TO HUMAN AND SUBHUMAN PRIMATE RETROVIRUSES

该项目旨在描述对人类的功能性免疫反应。 免疫缺陷病毒(HIV)，并鉴定病毒亚片段 诱导对HIV-1和HIV-2的保护性体液和细胞免疫 猴免疫缺陷病毒(SIV)。中和抗体的研究 MN分离株显示，滴度&GT；225与不太严重相关 感染艾滋病毒的儿童中的疾病。这一滴度也可以预测 年龄调整后正常中位数CD4的10%的患者的临床结果 细胞计数。滴度和效价高出225的患者经常遇到重大 临床事件的随访率高于滴度为225的患者。因此， 中和抗体的保存应考虑在被动和 主动免疫治疗策略。广泛的交叉中和 HIV-2和SIV之间反映了共同的中和表位。V3循环 这些病毒的序列似乎不构成线性 中和表位。表达构象的交替亚基 利用HIV-2和SIV作为疫苗模型可能需要表位。 对病毒变异和免疫逃逸的研究强调 替代构象决定的表位与V3一样重要 HIV-1中和循环，免疫压力并不是唯一的 对变种选择的影响。一个逆转的艾滋病毒逃逸突变体是 在长期培养中选择，因为较小的细胞病变效应。 对HIV-1、HIV-2和SIV的细胞免疫反应反映了与 此前已确定的HIV-1表位。一种交叉反应的鉴定 HIV-1和HIV-2包膜上的细胞毒性T淋巴细胞表位 用痘苗病毒-env重组体免疫小鼠可能有助于设计 广泛反应的疫苗。LIVE诱导的功能性免疫反应 载体，如减毒牛痘、禽痘和腺病毒，携带 目前正在对艾滋病毒基因进行评估。腺病毒-HIV-包膜重组体 展现出了巨大的希望。用不同的血清型顺序免疫的狗 重组腺病毒发展出高效价的HIV中和 抗体和腺病毒表达的HIV包膜有效地促进了 免疫反应。未来在黑猩猩身上进行的腺艾滋病毒疫苗试验将 评估活病毒挑战。

This project aims to delineate functional immune responses to the human immunodeficiency viruses (HIVs), and to identify viral subfragments which elicit protective humoral and cellular immunity to HIV-1 and -2 and simian immunodeficiency virus (SIV). Studies of neutralizing antibody to the MN isolate revealed that titers >225 were correlated with less severe disease in HIV-infected children. This titer was also predictive of clinical outcome in patients with >10% of normal median age-adjusted CD4 cell count. Patients with titers <225 more often encountered major clinical events in follow-up than patients with titers >225. Thus, preservation of neutralizing antibody should be considered in passive and active immune therapy strategies. Extensive cross-neutralizations seen between HIV-2 and SIV reflect common neutralizing epitopes. The V3 loop sequences of these viruses do not appear to constitute linear neutralizing epitopes. Alternate subunits expressing conformational epitopes may be needed to exploit HIV-2 and SIV as vaccine models. Studies of viral variation and immune escape have emphasized that alternate conformationally determined epitopes are as important as the V3 loop in HIV-1 neutralization, and immune pressure is not the sole influence on variant selection. A reverted HIV escape mutant was selected during long-term culture due to a lesser cytopathic effect. Cellular immune responses to HIV-1 and -2 and SIV reflect homology with previously identified HIV-1 epitopes. Identification of a cross-reactive cytotoxic T lymphocyte epitope in HIV-1 and -2 envelopes after immunization of mice with vaccinia-env recombinants may assist design of broadly reactive vaccines. Functional immune responses elicited by live vectors, such as attenuated vaccinia, avipox, and adenovirus, carrying HIV genes are being assessed. Adenovirus-HIV-envelope recombinants have shown great promise. Dogs immunized sequentially with distinct serotypes of adeno-HIV recombinants developed high-titer HIV neutralizing antibodies, and adenovirus expressed HIV envelope effectively boosted the immune response. Future trials of adeno-HIV vaccines in chimpanzees will assess a live virus challenge.