Fanales-Belasio Emanuele, Cafaro Aurelio, Cara Andrea, Negri Donatella R M, Fiorelli Valeria, Butto Stefano, Moretti Sonia, Maggiorella Maria Teresa, Baroncelli Silvia, Michelini Zuleika, Tripiciano Antonella, Sernicola Leonardo, Scoglio Arianna, Borsetti Alessandra, Ridolfi Barbara, Bona Roberta, Ten Haaft Peter, Macchia Iole, Leone Pasqualina, Pavone-Cossut Maria Rosaria, Nappi Filomena, Vardas Eftyhia, Magnani Mauro, Laguardia Elena, Caputo Antonella, Titti Fausto, Ensoli Barbara
Laboratory of Virology, Istituto Superiore di Sanità, Rome, Italy.
DNA Cell Biol. 2002 Sep;21(9):599-610. doi: 10.1089/104454902760330138.
Vaccination against human immunodeficiency virus (HIV)-1 infection requires candidate antigen(s) (Ag) capable of inducing an effective, broad, and long-lasting immune response against HIV-1 despite mutation events leading to differences in virus clades. The HIV-1 Tat protein is more conserved than envelope proteins, is essential in the virus life cycle and is expressed very early upon virus entry. In addition, both humoral and cellular responses to Tat have been reported to correlate with a delayed progression to disease in both humans and monkeys. This suggested that Tat is an optimal target for vaccine development aimed at controlling virus replication and blocking disease onset. Here are reviewed the results of our studies including the effects of the Tat protein on monocyte-derived dendritic cells (MDDCs) that are key antigen-presenting cells (APCs), and the results from vaccination trials with both the Tat protein or tat DNA in monkeys. We provide evidence that the HIV-1 Tat protein is very efficiently taken up by MDDCs and promotes T helper (Th)-1 type immune responses against itself as well as other Ag. In addition, a Tat-based vaccine elicits an immune response capable of controlling primary infection of monkeys with the pathogenic SHIV89.6P at its early stages allowing the containment of virus spread. Based on these results and on data of Tat conservation and immune cross-recognition in field isolates from different clades, phase I clinical trials are being initiated in Italy for both preventive and therapeutic vaccination.
针对人类免疫缺陷病毒（HIV）-1感染的疫苗接种需要候选抗原，该抗原能够诱导针对HIV-1的有效、广泛且持久的免疫反应，尽管突变事件会导致病毒进化枝出现差异。HIV-1反式激活蛋白（Tat）比包膜蛋白更保守，在病毒生命周期中至关重要，并且在病毒进入后很早就会表达。此外，据报道，对Tat的体液免疫和细胞免疫反应均与人类和猴子疾病进展延迟相关。这表明Tat是旨在控制病毒复制和阻止疾病发作的疫苗开发的最佳靶点。本文综述了我们的研究结果，包括Tat蛋白对关键抗原呈递细胞——单核细胞衍生树突状细胞（MDDC）的影响，以及在猴子中使用Tat蛋白或tat DNA进行疫苗试验的结果。我们提供的证据表明，HIV-1 Tat蛋白能被MDDC非常有效地摄取，并促进针对自身以及其他抗原的辅助性T细胞（Th）1型免疫反应。此外，基于Tat的疫苗能引发免疫反应，在早期阶段控制致病性猿猴-人免疫缺陷病毒89.6P（SHIV89.6P）对猴子的原发性感染，从而抑制病毒传播。基于这些结果以及不同进化枝野外分离株中Tat保守性和免疫交叉识别的数据，意大利正在启动I期预防性和治疗性疫苗临床试验。
