Maggiorella Maria Teresa, Baroncelli Silvia, Michelini Zuleika, Fanales-Belasio Emanuele, Moretti Sonia, Sernicola Leonardo, Cara Andrea, Negri Donatella R M, Buttò Stefano, Fiorelli Valeria, Tripiciano Antonella, Scoglio Arianna, Caputo Antonella, Borsetti Alessandra, Ridolfi Barbara, Bona Roberta, ten Haaft Peter, Macchia Iole, Leone Pasqualina, Pavone-Cossut Maria Rosaria, Nappi Filomena, Ciccozzi Massimo, Heeney Jonathan, Titti Fausto, Cafaro Aurelio, Ensoli Barbara
Laboratory of Virology, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, Italy.
Vaccine. 2004 Sep 3;22(25-26):3258-69. doi: 10.1016/j.vaccine.2004.03.009.
Vaccination with a biologically active Tat protein or tat DNA contained infection with the highly pathogenic SHIV89.6P virus, preventing CD4 T-cell decline and disease onset. Here we show that protection was prolonged, since neither CD4 T-cell decline nor active virus replication was observed in all vaccinated animals that controlled virus replication up to week 104 after the challenge. In contrast, virus persisted and replicated in peripheral blood mononuclear cells and lymph nodes of infected animals, two of which died. Tat-specific antibody, CD4 and CD8 T-cell responses were high and stable only in the animals controlling the infection. In contrast, Gag-specific antibody production and CD4 and CD8 T-cell responses were consistently and persistently positive only in the monkeys that did not control primary virus replication. These results indicate that vaccination with Tat protein or DNA induced long-term memory Tat-specific immune responses and controlled primary infection at its early stages allowing a long-term containment of virus replication and spread in blood and tissues.
用具有生物活性的Tat蛋白或tat DNA进行疫苗接种可预防高致病性SHIV89.6P病毒感染,防止CD4 T细胞减少和疾病发作。我们在此表明,保护作用得以延长,因为在所有接种疫苗且在攻击后长达104周控制病毒复制的动物中,均未观察到CD4 T细胞减少或活跃病毒复制。相比之下,病毒在受感染动物的外周血单核细胞和淋巴结中持续存在并复制,其中两只动物死亡。仅在控制感染的动物中,Tat特异性抗体、CD4和CD8 T细胞反应高且稳定。相比之下,仅在未控制原发性病毒复制的猴子中,Gag特异性抗体产生以及CD4和CD8 T细胞反应持续呈阳性。这些结果表明,用Tat蛋白或DNA进行疫苗接种可诱导长期记忆性Tat特异性免疫反应,并在早期阶段控制原发性感染,从而长期遏制病毒在血液和组织中的复制和传播。