ENHANCED IMMUNITY TO HUMAN-IMMUNODEFICIENCY-VIRUS (HIV) ENVELOPE ELICITED BY A COMBINED VACCINE REGIMEN CONSISTING OF PRIMING WITH A VACCINIA RECOMBINANT EXPRESSING HIV ENVELOPE AND BOOSTING WITH GP160-PROTEIN
ENHANCED IMMUNITY TO HUMAN-IMMUNODEFICIENCY-VIRUS (HIV) ENVELOPE ELICITED BY A COMBINED VACCINE REGIMEN CONSISTING OF PRIMING WITH A VACCINIA RECOMBINANT EXPRESSING HIV ENVELOPE AND BOOSTING WITH GP160-PROTEIN
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DOI：
10.1073/pnas.90.5.1882
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发表时间：
1993-03-01
影响因子：
11.1
通讯作者：
GREENBERG, PD
中科院分区：
文献类型：
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作者：
COONEY, EL;MCELRATH, MJ;GREENBERG, PD
传播研究表明，最佳的人类免疫缺陷病毒 1 型 (HIV-1) 疫苗应诱导中和抗体和溶细胞 T 细胞，以消除游离病毒和受感染的细胞。在健康 HIV-1 血清阴性人群中进行了一项联合 HIV-1 疫苗方案（IIIB 株）的 I 期试验，该方案包括用表达 HIV-1 包膜的重组牛痘 (vac/env) 病毒进行初免，并用源自重组杆状病毒 (rgp160) 的 gp160 糖蛋白进行加强。单独使用 vac/env 或单独使用 rgp160 进行免疫后检测到的 T 细胞和抗体反应通常程度较低且短暂，并且没有受试者产生中和抗体。相比之下，联合方案的接受者在体外表现出对同源 HIV-1 抗原的 T 细胞增殖反应，比单独使用任一疫苗的反应高 3 至 10 倍，并且这些反应在 75% 的接受者中持续超过 18 个月。此外，还检测到CD8+和CD4+溶细胞T细胞。联合治疗方案的所有接受者均产生了针对同源 HIV 包膜的抗体反应（滴度为 1:800 至 1:102,400），并且在 13 名接受者中的 7 名中检测到中和抗体。因此，用活病毒疫苗进行免疫，然后用可溶性蛋白进行加强，为诱导 HIV 疫苗所需的广泛免疫提供了希望。
Transmission studies have suggested that an optimal human immunodeficiency virus type 1 (HIV-1) vaccine should induce both neutralizing antibodies and cytolytic T cells to eliminate free virus and infected cells. A phase I trial in healthy HIV-1-seronegative persons was conducted with a combination HIV-1 vaccine regimen (strain IIIB) consisting of priming with a recombinant vaccinia (vac/env) virus expressing HIV-1 envelope and boosting with a gp160 glycoprotein derived from a recombinant baculovirus (rgp160). T-cell and antibody responses detected after immunization with either vac/env alone or rgp160 alone were generally of low magnitude and transient, and no subject developed neutralizing antibodies. In contrast, recipients of the combination regimen demonstrated in vitro T-cell proliferative responses to homologous HIV-1 antigens that were 3- to 10-fold higher than responses with either vaccine alone, and these responses were sustained for >18 months in 75% of recipients. Moreover, both CD8+ and CD4+ cytolytic T cells were detected. Antibody responses (titer, 1:800 to 1:102,400) to homologous HIV envelope developed in all recipients of the combination regimen, and neutralizing antibodies were detected in 7 of 13. Thus, immunization with a live virus vaccine followed by boosting with a soluble protein offers promise for inducing the broad immunity needed in an HIV vaccine.