HUMORAL AND CELLULAR IMMUNE RESPONSES TO HUMAN AND NONHUMAN PRIMATE RETROVIRUSES

艾滋病疫苗的开发研究主要集中在载体方面 接近了。用腺病毒感染人类免疫缺陷的黑猩猩 病毒1型(HIV-1)(MN)重组和HIV-1(SF2)增强 用SF2分离物攻击信封。同时进行模拟免疫的 黑猩猩很快被感染，3只黑猩猩中和 抗体不受SF2感染。另一只黑猩猩 产生了细胞毒性T淋巴细胞反应，但没有中和抗体 也受到保护，这表明细胞介导的免疫在 疫苗保护。对更高剂量挑战的评估正在进行中。 腺病毒宿主范围突变猴免疫缺陷病毒的研究 重组的目的是评估恒河猴的黏膜挑战。 猕猴。在此之前，对恒河猴进行减毒免疫 痘病毒HIV-2重组体被证明能引发持久的 预防艾滋病毒-2病毒的挑战。此外，免疫接种 减毒痘病毒HIV-1重组体对 一场HIV-2挑战。最近的一项研究表明，长期的免疫接种 时间表对于保护性免疫的发展是必要的。正在进行中 使用更多动物的研究正在调查免疫力 与保护相关的反应，特别是细胞介导的方面 免疫、CD8+细胞抑制因子的作用和中和 外周血淋巴细胞和巨噬细胞中的初级分离株。在……里面 人类，免疫保护的相关因素正在进行不一致的研究 在进步快或慢的夫妇和孩子身上。生物学和 HIV-1逃逸突变体的分子分析，旨在识别 病毒包膜的结构和功能重要区域， 继续精确定位CD4结合区对许多 病毒与宿主的相互作用。对CD4结合区进行建模的研究已经 鉴定的构象受限的多肽，其功能和 抗原性模拟gp120的CD4区。最后，分子 流行病学研究已经确定了艾滋病病毒的几个亚型 人口稠密的非洲国家尼日利亚。这一信息将是 在针对特定地域的疫苗开发中有用 在地区以及全球有效疫苗的设计方面也是如此。

Developmental studies for AIDS vaccines have focussed on vectored approaches. Chimpanzees primed with adenovirus human immunodeficiency virus type 1 (HIV-1) (MN) recombinants and boosted with HIV-1 (SF2) envelope were challenged with the SF2 isolate. While a mock-immunized chimpanzee quickly became infected, 3 chimpanzees with neutralizing antibodies were protected from SF2 infection. Another chimpanzee which developed a cytotoxic T-lymphocyte response but no neutralizing antibody was also protected, suggesting a role for cell-mediated immunity in vaccine protection. Evaluation of a higher dose challenge is ongoing. Studies using adenovirus host range mutant-simian immunodeficiency virus recombinants are aimed at evaluating a mucosal challenge in rhesus macaques. Previously, immunization of rhesus macaques with attenuated poxvirus HIV-2 recombinants has been shown to elicit long-lasting protection against an HIV-2 challenge. In addition, immunization with attenuated poxvirus HIV-1 recombinants caused cross-protection against an HIV-2 challenge. A recent study suggests that a long immunization schedule is necessary for development of protective immunity. Ongoing studies using larger numbers of animals are investigating immune responses associated with protection, especially aspects of cell-mediated immunity, the role of a CD8+ cell suppressor factor, and neutralization of primary isolates in peripheral blood lymphocytes and macrophages. In humans, immune correlates of protection are being studied in discordant couples and in children who are fast or slow progressors. Biologic and molecular analyses of HIV-1 escape mutants, designed to identify structurally and functionally important regions of the viral envelope, continue to pinpoint the CD4 binding region as critical for numerous virus-host interactions. Studies modeling the CD4 binding region have identified conformationally constrained peptides which functionally and antigenically mimic the CD4 region of gp120. Finally, molecular epidemiologic studies have identified several HIV-1 subtypes in the highly populous African nation of Nigeria. This information will be useful in development of vaccines targeted to particular geographic regions as well as in design of globally effective vaccines.