Cafaro A, Caputo A, Maggiorella M T, Baroncelli S, Fracasso C, Pace M, Borsetti A, Sernicola L, Negri D R, Ten Haaft P, Betti M, Michelini Z, Macchia I, Fanales-Belasio E, Belli R, Corrias F, Buttò S, Verani P, Titti F, Ensoli B
Laboratory of Virology, Istituto Superiore di Sanità, Rome, Italy.
J Med Primatol. 2000 Aug;29(3-4):193-208. doi: 10.1034/j.1600-0684.2000.290313.x.
The Tat protein of human immunodeficiency virus (HIV) is produced very early after infection, plays a key role in the virus life cycle and in acquired immunodeficiency syndrome (AIDS) pathogenesis, is immunogenic and well conserved among all virus clades. Notably, a Tat-specific immune response correlates with non-progression to AIDS. Here, we show that a vaccine based on the Tat protein of HIV blocks primary infection with the simian/human immunodeficiency virus (SHIV)89.6P and prevents the CD4 T cell decline and disease onset in cynomolgus monkeys. No signs of virus replication were found in five out of seven vaccinated macaques for almost 1 year of follow-up. Since the inoculated virus (derived from rhesus or from cynomolgus macaques) is shown to be highly pathogenic in cynomolgus macaques, the results indicate efficacy of Tat vaccination in protection against highly pathogenic virus challenge. Finally, the studies of the Tat-specific immunological responses indicate a correlation of protection with a cytotoxic T cell response. Thus, a Tat-based vaccine is a promising candidate for preventive and therapeutic vaccination in humans.
人类免疫缺陷病毒（HIV）的反式激活蛋白（Tat）在感染后很早便会产生，在病毒生命周期以及获得性免疫缺陷综合征（AIDS）发病机制中发挥关键作用，具有免疫原性且在所有病毒分支中高度保守。值得注意的是，针对Tat的免疫反应与不发展为AIDS相关。在此，我们表明基于HIV Tat蛋白的疫苗可阻断猿猴/人类免疫缺陷病毒（SHIV）89.6P的原发性感染，并防止食蟹猴出现CD4 T细胞减少和疾病发作。在长达近1年的随访中，7只接种疫苗的猕猴中有5只未发现病毒复制迹象。由于接种的病毒（源自恒河猴或食蟹猴）在食蟹猴中显示出高致病性，这些结果表明Tat疫苗接种在抵御高致病性病毒攻击方面具有有效性。最后，对Tat特异性免疫反应的研究表明保护作用与细胞毒性T细胞反应相关。因此，基于Tat的疫苗是人类预防性和治疗性疫苗接种的一个有前景的候选者。
