Safety profile of phase I and II preventive HIV type 1 envelope vaccination: Experience of the NIAID AIDS Vaccine Evaluation Group
Safety profile of phase I and II preventive HIV type 1 envelope vaccination: Experience of the NIAID AIDS Vaccine Evaluation Group
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DOI：
10.1089/aid.1997.13.1163
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发表时间：
1997-09-20
影响因子：
1.5
通讯作者：
Wescott, SL
中科院分区：
文献类型：
--
作者：
Keefer, MC;Wolff, M;Wescott, SL
由美国国家艾滋病规划署赞助的艾滋病疫苗评估小组成立于1988年，目的是对候选的预防性艾滋病毒-1疫苗进行I/II期临床试验。该报告包括来自1398名hiv阴性健康志愿者的安全性数据，这些志愿者参加了25项I期和1项II期多中心、随机、双盲研究，评估了7种重组HIV-1包膜疫苗、2种V3环合成肽疫苗和2种痘病毒载体重组包膜疫苗。除三项研究外，所有研究均采用安慰剂对照；安慰剂是单独的佐剂，或者在重组痘病毒疫苗的研究中，它是没有基因插入或非hiv基因插入的载体。所有候选疫苗通常耐受良好。唯一明显与疫苗接种相关的不良反应是与佐剂相关的偶尔急性局部和全身反应。三种佐剂与中度至重度局部反应特别相关：明矾加脱氧胆酸盐（ImmunoAg）， MTP-PE （Biocine Corp.）和QS21 （Genentech, Inc.）。MTP-PE还与自限性严重全身反应有关，在接种候选疫苗后，没有严重的不良实验室毒性，也没有明显的免疫抑制事件的证据。少数志愿者出现的症状可能与潜在的免疫病理机制有关（皮疹、溶血性贫血、关节痛），但症状较轻，发生率较低。11名志愿者在参与期间或之后被诊断为恶性肿瘤，这在国家癌症研究所SEER（癌症监测、流行病学和最终结果报告项目）数据库预测的病例数的95%置信区间内。总之，基于包膜的重组或合成候选HIV-1疫苗似乎是安全的，这项工作为测试日益复杂的候选HIV-1疫苗铺平了道路。
The NIAID-sponsored AIDS Vaccine Evaluation Group was established in 1988 to perform phase I/II clinical trials with candidate preventive HIV-1 vaccines. This report includes safety data from 1398 HIV-negative, healthy volunteers who were enrolled into 25 phase I and 1 phase II multicentered, randomized, double-blind studies evaluating seven recombinant HIV-1 envelope vaccines, two V3 loop synthetic peptide vaccines, and two live poxvirus-vectored recombinant envelope vaccines. All studies but three were placebo controlled; the placebo was either the adjuvant alone or, in studies of recombinant poxvirus vaccines, it was the vector with no gene insert or a non-HIV gene insert, All candidate vaccines were generally well tolerated. The only adverse effects that were clearly related to vaccination were occasional acute local and systemic reactions that were associated with the adjuvants. Three adjuvants in particular were associated with moderate to severe local reactions: alum plus deoxycholate (ImmunoAg), MTP-PE (Biocine Corp.), and QS21 (Genentech, Inc.). MTP-PE was also associated with self-limited severe systemic reactions, There were no serious adverse laboratory toxicities and no evidence of significant immunosuppressive events after receipt of the candidate vaccines. A few volunteers experienced symptoms that might relate to an underlying immunopathologic mechanism (rash, hemolytic anemia, arthralgia), but their presentations were mild and their incidence was low. Eleven volunteers were diagnosed with malignancies during or after their participation, which was within the 95% confidence interval of the number of cases predicted by the National Cancer Institute SEER (Program for cancer surveillance, epidemiology, and end result reporting) database. In conclusion, the envelope-based recombinant or synthetic candidate HIV-1 vaccines appear to be safe and this work has prepared the way for the testing of increasingly complex candidate HIV-1 vaccines.