Division of Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
J Virol. 2012 Sep;86(18):9583-9. doi: 10.1128/JVI.00996-12. Epub 2012 Jul 3.
A comprehensive vaccine for human immunodeficiency virus type 1 (HIV-1) would block HIV-1 acquisition as well as durably control viral replication in breakthrough infections. Recent studies have demonstrated that Env is required for a vaccine to protect against acquisition of simian immunodeficiency virus (SIV) in vaccinated rhesus monkeys, but the antigen requirements for virologic control remain unclear. Here, we investigate whether CD8(+) T lymphocytes from vaccinated rhesus monkeys mediate viral inhibition in vitro and whether these responses predict virologic control following SIV challenge. We observed that CD8(+) lymphocytes from 23 vaccinated rhesus monkeys inhibited replication of SIV in vitro. Moreover, the magnitude of inhibition prior to challenge was inversely correlated with set point SIV plasma viral loads after challenge. In addition, CD8 cell-mediated viral inhibition in vaccinated rhesus monkeys correlated significantly with Gag-specific, but not Pol- or Env-specific, CD4(+) and CD8(+) T lymphocyte responses. These findings demonstrate that in vitro viral inhibition following vaccination largely reflects Gag-specific cellular immune responses and correlates with in vivo virologic control following infection. These data suggest the importance of including Gag in an HIV-1 vaccine in which virologic control is desired.
一种针对人类免疫缺陷病毒 1 型（HIV-1）的全面疫苗不仅可以阻止 HIV-1 的感染，还可以在突破感染时持久地控制病毒复制。最近的研究表明，Env 对于疫苗预防接种恒河猴感染猴免疫缺陷病毒（SIV）是必需的，但对于病毒学控制的抗原要求仍不清楚。在这里，我们研究了接种疫苗的恒河猴的 CD8(+)T 淋巴细胞是否在体外介导病毒抑制，以及这些反应是否可以预测 SIV 挑战后的病毒学控制。我们观察到，来自 23 只接种疫苗的恒河猴的 CD8(+)淋巴细胞可以在体外抑制 SIV 的复制。此外，在挑战之前的抑制程度与挑战后 SIV 血浆病毒载量的设定点呈负相关。此外，在接种疫苗的恒河猴中，CD8 细胞介导的病毒抑制与 Gag 特异性，但与 Pol 或 Env 特异性，CD4(+)和 CD8(+)T 淋巴细胞反应显著相关。这些发现表明，接种疫苗后的体外病毒抑制在很大程度上反映了 Gag 特异性细胞免疫反应，并与感染后的体内病毒学控制相关。这些数据表明，在希望控制病毒学的 HIV-1 疫苗中包含 Gag 的重要性。
