HUMORAL AND CELLULAR IMMUNE RESPONSES TO HUMAN AND NONHUMAN PRIMATE RETROVIRUSES

组合艾滋病疫苗，使用活重组载体作为启动剂 紧随其后的是蛋白质增强剂接种，这是有希望的。 腺病毒(Ad)-HIV-1(MN)包膜重组体和gp120(SF2) 菌株)可以保护黑猩猩免受低剂量和高剂量的照射 感染HIV-1(SF2)。重大进展包括以下几点 要点：1)只需1次涂抹即可实现持久防护 免疫接种和2个蛋白质增强剂，或2个初级疫苗和1个增强剂；2) 所产生的高滴度中和抗体是持久的； 一只受保护的黑猩猩缺乏中和抗体，但拥有 HIV包膜特异性细胞毒性T淋巴细胞(CTL)被保护 低剂量挑战，首次表明CTL在 疫苗保护；4)疫苗方案引起的抗体能够 中和初级分离株，以前没有用 其他方法；5)针对高剂量挑战的保护 介入性加强接种持续了50周。这个 仅通过广告信封启动即可实现保护 GP120增强。预计将从类似的 将HIV Gag和nef基因和基因产物结合在一起的方法。 在猕猴的进一步疫苗研究中使用了一种Ad5宿主范围突变 携带SIV包膜基因的载体，与天然SIV结合 包膜亚基。这种方法引发了幽默、细胞和 免疫猕猴的粘膜免疫反应。粘膜免疫 尤其令人鼓舞，因为大约95%的艾滋病毒 世界范围内的传播跨越粘膜屏障。的能力 这种疫苗方法可以预防阴道内和直肠内感染 传输情况正在评估中。类似的优质提振方法有 使用减毒痘病毒载体作为疫苗进行 车辆。早期的研究表明，艾滋病毒-1免疫接种 重组体和蛋白质对HIV-2具有保护作用 挑战，表明发展单一的全球有效的 艾滋病疫苗或许是可能的。我们正在扩大这项研究以证实 与以前的结果相比较，确定了交叉保护的性质 豁免权。最后，对免疫逃逸变体的研究结果 强调了对包膜至关重要的CD4结合位点区域 功能和免疫识别。我们已经证明了在构象上 来自CD4结合位点区域的限制性螺旋多肽 对本机站点进行适当的建模，并为 这些不同的病毒，如HIV-1，HIV-2和SIV，是如何识别的 CD_4受体。使用这种螺旋肽的疫苗方法有 正在进行中。

Combination AIDS vaccines, using live recombinant vectors as priming vehicles followed by protein booster inoculations, are promising. Adenovirus (Ad)-HIV-1(MN) envelope recombinants followed by gp120 (SF2 strain) have protected chimpanzees from both low- and high-dose infection with HIV-1(SF2). Significant advances include the following points: 1) Long-lasting protection can be achieved with only 1 priming immunization and 2 protein boosters, or 2 primings and 1 booster; 2) the high-titered neutralizing antibodies elicited were persistent; 3) one protected chimpanzee lacking neutralizing antibodies but possessing HIV envelope-specific cytotoxic T-lymphocytes (CTL) was protected from low-dose challenge, suggesting for the first time a role for CTLs in vaccine protection; 4) the vaccine regimen elicited antibodies capable of neutralizing primary isolates, not previously demonstrated with other approaches; 5) protection against a high-dose challenge with no intervening booster inoculation persisted for >50 weeks. The protection that was achieved resulted from only Ad-envelope priming and gp120 boosting. Enhanced protection would be expected from a similar approach incorporating HIV gag and nef genes and gene products. Further vaccine studies in macaques have used an Ad 5 host range mutant vector carrying the SIV envelope gene, combined with a native SIV envelope subunit. This approach elicited humoral, cellular, and mucosal immune responses in immunized macaques. The mucosal immunity is particularly encouraging, as approximately 95% of all HIV transmissions worldwide occur across mucosal barriers. The ability of this vaccine approach to protect against intravaginal and intrarectal transmission is being evaluated. Similar prime-boost approaches are being carried out using attenuated poxvirus vectors as vaccine vehicles. Earlier studies showed that immunization with HIV-1 recombinants and proteins resulted in protection against HIV-2 challenge, suggesting that development of a single globally effective AIDS vaccine might be possible. We are expanding this study to confirm the previous result and identify the nature of the cross-protective immunity. Finally, results of studies on immune escape variants have highlighted the CD4 binding site region as crucial for envelope function and immune recognition. We have shown that a conformationally constrained helical peptide from the CD4 binding site region appropriately models the native site and provides an explanation for how such disparate viruses, as HIV-1, HIV-2, and SIV, can all recognize the CD4 receptor. Vaccine approaches using this helical peptide are in progress.