Shiver J W, Perry H C, Davies M E, Freed D C, Liu M A
Department of Virus and Cell Biology, Merck Research Laboratories, West Point, Pennsylvania 19486, USA.
Ann N Y Acad Sci. 1995 Nov 27;772:198-208. doi: 10.1111/j.1749-6632.1995.tb44745.x.
Expression vectors encoding either HIV-1 gp160/rev, gp120, or rev alone were used for direct vaccination of mice and nonhuman primates. Each vaccine elicited long-lived (> 7 months) helper T cell responses in mice and monkeys as measured by in vitro proliferation of splenocytes following recombinant antigen treatment. Cytokine assays of the cell supernatants showed that approximately 100-fold more gamma-interferon than IL-4 was secreted during culture indicating that these vaccines elicited TH1-like responses. CD8+ CTL activities were also observed both in mice and rhesus. The gp120 and gp160/rev vaccines elicited antigen-specific antibodies, although these responses were more variable and lower magnitude for gp160/rev, and gp120 DNA-vaccinated African green monkeys had moderate levels of neutralizing antibodies. No antibodies were found against rev (an intracellular protein) with either rev vaccine. Similar antibody titers were obtained for gp120 by either intramuscular or intradermal injection although T cell responses were generally lower by intradermal route. These results indicate that DNA vaccines may provide a powerful means to elicit cellular and humoral immune responses against HIV.
编码HIV-1 gp160/rev、gp120或单独的rev的表达载体被用于直接对小鼠和非人类灵长类动物进行疫苗接种。通过重组抗原处理后脾细胞的体外增殖测定,每种疫苗在小鼠和猴子中均引发了长寿(>7个月)的辅助性T细胞反应。细胞上清液的细胞因子检测显示,培养期间分泌的γ-干扰素比IL-4多约100倍,表明这些疫苗引发了类似TH1的反应。在小鼠和恒河猴中也观察到了CD8+ CTL活性。gp120和gp160/rev疫苗引发了抗原特异性抗体,尽管对于gp160/rev,这些反应的变异性更大且强度更低,并且接种gp120 DNA疫苗的非洲绿猴具有中等水平的中和抗体。两种rev疫苗均未发现针对rev(一种细胞内蛋白)的抗体。通过肌肉注射或皮内注射获得的gp120抗体滴度相似,尽管皮内途径的T细胞反应通常较低。这些结果表明,DNA疫苗可能是引发针对HIV的细胞免疫和体液免疫反应的有力手段。