THE SAFETY AND IMMUNOGENICITY OF A HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 (HIV-1) RECOMBINANT GP160 CANDIDATE VACCINE IN HUMANS
THE SAFETY AND IMMUNOGENICITY OF A HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 (HIV-1) RECOMBINANT GP160 CANDIDATE VACCINE IN HUMANS
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DOI：
10.7326/0003-4819-114-2-119
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发表时间：
1991-01-15
影响因子：
39.2
通讯作者：
KOFF, WC
中科院分区：
文献类型：
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作者：
DOLIN, R;GRAHAM, BS;KOFF, WC
目的：为了评价人类免疫缺陷病毒1型（HIV-1）重组包膜糖蛋白（rgp 160）候选疫苗在人体中的安全性和免疫原性，受试者：将HIV-1血清阴性的健康成人（72名）随机分配到四组之一。受试者被随机分配接受40或80 μ g的rgp 160、10 μ g的B型肝炎疫苗或安慰剂，分三次给药（在第0、30和180天），并在第540天选择性非盲施用第四剂量。测量和主要结果：在超过21个月的随访期间，未遇到临床或实验室毒性。免疫接种对淋巴细胞计数、促有丝分裂反应或迟发型超敏反应无影响。在接受40或80 μ g剂量rgp 160的33名受试者中，有30名（91%; 95%CI，71%至97%）观察到通过蛋白质印迹法检测到的对HIV包膜蛋白的血清抗体应答，并且最常见的是弱反应强度。在第二次给药后首先通过蛋白质印迹法记录反应。在第三次给药后，其频率显著增加，并在接下来的12至18个月内下降。第4次给药导致5/24例受试者血清中出现同源中和活性（21%; CI，7%-37%），以及6/24例受试者血清中出现补体介导的抗体依赖性增强（25%; CI，10%-42%）。酶联免疫吸附试验（ELISA）检测抗体应答的频率低于Western blot，并且这些应答持续的时间较短。rgp160的给药耐受性良好且安全，在第三和第四剂量给药后通过Western印迹法产生高比率的抗体应答，并在第四次给药后在一些受试者中产生血清中和活性和补体介导的抗体依赖性增强。
Objective: To evaluate the safety and immunogenicity of a human immunodeficiency virus type 1 (HIV-1) recombinant envelope glycoprotein (rgp160) candidate vaccine in humans.Subjects: Healthy adults (72) who were seronegative for HIV-1 were randomly assigned to one of four groups.Interventions: The subjects were randomly assigned to receive 40 or 80-mu-g of rgp160, 10-mu-g of hepatitis B vaccine, or placebo in three doses (on days 0, 30, and 180), with an elective, nonblinded administration of a fourth dose on day 540.Measurements and Main Results: Neither clinical nor laboratory toxicity was encountered during a follow-up period exceeding 21 months. No effect of immunization was noted on lymphocyte counts, mitogenic responses, or delayed-type hypersensitivity. Serum antibody responses to HIV envelope proteins detected by Western blot were seen in 30 of 33 subjects (91%; 95% CI, 71% to 97%) receiving either 40- or 80-mu-g doses of rgp160 and were most commonly of weakly reactive intensity. Responses were first noted by Western blot after the second dose. They markedly increased in frequency after the third dose and declined over the next 12 to 18 months. The administration of a fourth dose resulted in homologous neutralizing activity in sera from 5 of 24 subjects (21%; CI, 7% to 37%) as well as in complement-mediated antibody-dependent enhancement in sera from 6 of 24 subjects (25%; CI, 10% to 42%). Antibody responses were detected by enzyme-linked immunosorbent assay (ELISA) less frequently than by Western blot, and these responses persisted for a shorter time.Conclusions: The administration of rgp160 was well tolerated and safe, resulted in a high rate of antibody response by Western blot after the administration of the third and fourth doses, and generated serum neutralizing activity and complement-mediated antibody-dependent enhancement in some subjects after the fourth dose.