HUMORAL AND CELLULAR IMMUNE RESPONSES TO HUMAN AND SUBHUMAN PRIMATE RETROVIRUSES

开发有效的逆转录病毒疫苗和免疫疗法 感染、生物学和免疫学变量 必须阐明病毒和宿主之间的平衡。 正在进行的研究 包括疫苗、生物制剂和 新型人类免疫缺陷病毒1型的分子特征 （HIV-1）分离株，影响以及免疫学和生物学后果 病毒变异性的选择压力。 免疫后， 用减毒痘病毒HIV-1或HIV-2重组体感染恒河猴， 引发蛋白质增强剂、体液和细胞免疫应答， 尽管这两项活动都与保护无关。 进一步研究 HIV-2猕猴模型表明，中和抗体可能 与保护有关。 腺病毒HIV-1重组体已被 在黑猩猩中显示出激发体液、细胞和粘膜免疫 模型 既往腺病毒血清状态和重组体数量 免疫调节免疫应答。一种新的血凝素分子 用V3环插入物， 豚鼠和恒河猴，并且可能被证明是有用的加强剂 免疫原 为了开发有针对性的艾滋病毒疫苗， 必须知道地理区域中的亚型。 HIV-1，而不是HIV-2， 在西非国家尼日利亚很流行。 生物 尼日利亚HIV-1分离株的分子特征显示， 新亚型 流行株的分子流行病学研究 尼日利亚正在进行。 病毒变异性是 研制有效的艾滋病疫苗。艾滋病毒逃逸突变体产生于 包括V3环和CD 4结合结构域在内的多种途径 gp120。 信封段的上下文也影响中和。 回复突变逃逸突变体显示功能和免疫 CD 4结合区，亮氨酸拉链区， 融合结构域，以及在包膜寡聚化后隐藏的gp 41区域。 为了避免免疫逃逸，免疫策略应该靶向保守的， 功能重要的区域，因此突变会导致非- 传染性病毒

To develop effective vaccines and immune therapies for retroviral infections, biologic and immunologic variables influencing the equilibrium between virus and host must be elucidated. Ongoing studies include the nature of immune responses elicited by vaccines, biologic and molecular characterization of novel human immunodeficiency virus type 1 (HIV-1) isolates, and effects and immunologic and biologic consequences of selection pressures on viral variability. Following immunization of rhesus macaques with attenuated poxvirus HIV-1 or HIV-2 recombinants and protein boosters, humoral and cellular immune responses were elicited, although neither activity correlated with protection. Further study of the HIV-2 macaque model suggested that neutralizing antibodies may be associated with protection. Adenovirus HIV-1 recombinants have been shown to elicit humoral, cellular, and mucosal immunity in the chimpanzee model. Prior adenovirus serostatus and the number of recombinant immunizations modulate immune responses. A novel hemagglutinin molecule with a V3 loop insert elicits high titered neutralizing antibodies in guinea pigs and rhesus macaques, and may prove useful as a booster immunogen. To develop targeted HIV vaccines, the prevalence of HIV subtypes in geographic locales must be known. HIV-1, not HIV-2, was shown to be prevalent in the West African nation of Nigeria. Biologic and molecular characterization of Nigerian HIV-1 isolates revealed a novel subtype. Molecular epidemiologic studies of isolates prevalent in Nigeria are proceeding. Viral variability presents a major obstacle to development of an effective HIV vaccine. HIV escape mutants arise from multiple pathways including the V3 loop and the CD4 binding domain on gp120. The context of envelope segments also influences neutralization. A revertant escape mutant revealed functional and immunologic relationships between the CD4 binding region, leucine zipper region, fusion domain, and a gp41 region hidden after envelope oligomerization. To avoid immune escape, immune strategies should target conserved, functionally important regions, so that mutation would lead to a non- infectious virus.