National AIDS Center, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
Vaccine. 2009 Dec 11;28(2):371-8. doi: 10.1016/j.vaccine.2009.10.038. Epub 2009 Oct 29.
The native HIV-1 Tat protein was chosen as vaccine candidate for phase I clinical trials based on its role in the natural infection and AIDS pathogenesis, on the association of Tat-specific immune response with the asymptomatic stage as well as on its sequence conservation among HIV clades. A randomized, double blind, placebo-controlled phase I study (ISS P-001) was conducted in healthy adult volunteers without identifiable risk of HIV infection. Tat was administered 5 times monthly, subcute in alum or intradermic alone at 7.5 microg, 15 microg or 30 microg, respectively (ClinicalTrials.gov identifier: NCT00529698). Vaccination with Tat resulted to be safe and well tolerated (primary endpoint) both locally and systemically. In addition, Tat induced both Th1 and Th2 type specific immune responses in all subjects (secondary endpoint) with a wide spectrum of functional antibodies that are rarely seen in natural infection, providing key information for further clinical development of the Tat vaccine candidate.
选择天然 HIV-1 Tat 蛋白作为 I 期临床试验的候选疫苗，是基于其在自然感染和艾滋病发病机制中的作用、Tat 特异性免疫反应与无症状期的关联以及 HIV 各群之间的序列保守性。在没有可识别的 HIV 感染风险的健康成年志愿者中进行了一项随机、双盲、安慰剂对照的 I 期研究（ISS P-001）。Tat 每月皮下注射 5 次，分别在明矾或皮内以 7.5μg、15μg 或 30μg 给药（ClinicalTrials.gov 标识符：NCT00529698）。Tat 疫苗接种在局部和全身均安全且耐受良好（主要终点）。此外，Tat 在所有受试者中诱导了 Th1 和 Th2 型特异性免疫反应（次要终点），产生了广泛的功能抗体，这些抗体在自然感染中很少见，为进一步开发 Tat 疫苗候选物提供了关键信息。
