Kovacs J A, Vasudevachari M B, Easter M, Davey R T, Falloon J, Polis M A, Metcalf J A, Salzman N, Baseler M, Smith G E
Critical Care Medicine Department, National Institutes of Health, Bethesda, Maryland 20892.
J Clin Invest. 1993 Aug;92(2):919-28. doi: 10.1172/JCI116667.
Development of an effective vaccine for prevention of infection with HIV would provide an important mechanism for controlling the AIDS epidemic. In the current study, the first clinical trial of a candidate HIV-1 vaccine initiated in the United States, the safety and immunogenicity of escalating doses (10-1,280 micrograms) of recombinant gp160 (rgp160), were evaluated in 138 HIV-negative volunteers. Maximal antibody responses, as evaluated by ELISA, were seen after immunization with three doses of 1,280 micrograms rgp160. Responses to some specific epitopes of HIV gp160, including the second conserved domain and the CD4 binding site, were seen more frequently than after natural infection. Neutralizing antibodies to the homologous HIV strain, but not heterologous strains, were induced by this regimen. Blastogenic responses to rgp160 were seen in most volunteers receiving at least two doses of > or = 20 micrograms. These envelope-specific T cell responses were also seen against heterologous strains of HIV. No major adverse reactions were seen after immunization. Thus, rgp160 is a safe and immunogenic candidate HIV vaccine; further studies are needed to determine if it will provide any clinical benefit in preventing HIV infection.
开发一种有效的预防HIV感染的疫苗将为控制艾滋病流行提供重要机制。在当前这项美国发起的首个候选HIV-1疫苗临床试验中，对138名HIV阴性志愿者评估了递增剂量（10 - 1280微克）重组gp160（rgp160）的安全性和免疫原性。通过ELISA评估，在接种三剂1280微克rgp160后观察到最大抗体反应。与自然感染后相比，对HIV gp160的一些特定表位（包括第二个保守结构域和CD4结合位点）的反应更频繁出现。该方案诱导出针对同源HIV毒株而非异源毒株的中和抗体。在大多数接受至少两剂≥20微克rgp160的志愿者中观察到对rgp160的增殖反应。这些包膜特异性T细胞反应也见于针对HIV异源毒株的情况。免疫后未观察到重大不良反应。因此，rgp160是一种安全且具有免疫原性的候选HIV疫苗；需要进一步研究以确定其在预防HIV感染方面是否会带来任何临床益处。
