Zagury D, Salaün J J, Bernard J, Dechazal L, Goussard B, Lurhuma Z
l'Institut P. et M. Curie, Université de Jussieu, Paris, France.
Med Trop (Mars). 1988 Oct-Dec;48(4):417-23.
The first experimental immunization of human against the AIDS retrovirus HIV-1 was started in a series of HIV seronegative healthy volunteers in november 1986. Priming used a vaccinia virus recombinant (V25) expressing Gp 160 env determinants of HTLV III B at the surface of infected cells. This priming which induced a weak immune reaction was performed on HIV seronegative French and Zaïrian individuals living in Zaïre (Kinshasa). These results prompted to boost the primary immune response. Four different protocols were used: slow drip intravenous infusion with paraformaldehyde fixed autologous cells infected with V25 (first protocol), repeated scarification with V25 for the second protocol. The third protocol used scarifications with fragment of Gp 120 env protein, and the fourth protocol used intramuscular injections of purified autologous cell membrane infected with V25. Results of the immune reaction obtained after these boosts: The three last protocols showed a cell mediated immunity (CMI) that not significantly enhanced in comparison with CMI obtained after V25 priming alone. Moreover, the sera showed low and variable neutralizing antibodies titers one to four months after boosting. By contrast boosting with V25 infected fixed cells (D.Z. individual) provide strong humoral and cellular group specific anamnestic immune response. Indeed, high levels of antibodies to viral envelope and neutralizing antibodies against divergent HIV-1 strains were observed. Group specific CMI and cell mediated cytotoxicity were enhanced by boosts. Skin-tests showed high mediated and delayed hypersensitivity to GP 160 in vivo. For the first time, these results show that an immune stage against HIV can be obtained in a man.
1986年11月,在一系列HIV血清阴性的健康志愿者中开始了首例针对艾滋病逆转录病毒HIV-1的人体实验性免疫接种。初次免疫使用了一种痘苗病毒重组体(V25),它在受感染细胞表面表达HTLV III B的Gp 160 env决定簇。这种初次免疫在居住在扎伊尔(金沙萨)的法国和扎伊尔HIV血清阴性个体中进行,诱导了较弱的免疫反应。这些结果促使人们增强初次免疫反应。使用了四种不同的方案:第一种方案是用经多聚甲醛固定的感染V25的自体细胞进行缓慢静脉滴注;第二种方案是用V25反复划痕;第三种方案是用Gp 120 env蛋白片段进行划痕;第四种方案是肌肉注射感染V25的纯化自体细胞膜。这些增强免疫后获得的免疫反应结果如下:后三种方案显示出细胞介导免疫(CMI),与单独用V25进行初次免疫后获得的CMI相比,没有显著增强。此外,在增强免疫后一到四个月,血清显示出低且变化不定的中和抗体滴度。相比之下,用感染V25的固定细胞(D.Z.个体)进行增强免疫则产生了强烈的体液和细胞群体特异性回忆免疫反应。确实,观察到了针对病毒包膜的高水平抗体以及针对不同HIV-1毒株的中和抗体。增强免疫提高了群体特异性CMI和细胞介导的细胞毒性。皮肤试验显示在体内对GP 160有高度介导的迟发型超敏反应。这些结果首次表明,在人体中可以获得针对HIV的免疫阶段。