Vaccine Research Center, NIAID, National Institutes of Health, Bethesda, Maryland, USA.
J Virol. 2012 Aug;86(15):7760-70. doi: 10.1128/JVI.00599-12. Epub 2012 May 16.
The RV144 trial demonstrated that an experimental AIDS vaccine can prevent human immunodeficiency virus type 1 (HIV-1) infection in humans. Because of its limited efficacy, further understanding of the mechanisms of preventive AIDS vaccines remains a priority, and nonhuman primate (NHP) models of lentiviral infection provide an opportunity to define immunogens, vectors, and correlates of immunity. In this study, we show that prime-boost vaccination with a mismatched SIV envelope (Env) gene, derived from simian immunodeficiency virus SIVmac239, prevents infection by SIVsmE660 intrarectally. Analysis of different gene-based prime-boost immunization regimens revealed that recombinant adenovirus type 5 (rAd5) prime followed by replication-defective lymphocytic choriomeningitis virus (rLCMV) boost elicited robust CD4 and CD8 T-cell and humoral immune responses. This vaccine protected against infection after repetitive mucosal challenge with efficacies of 82% per exposure and 62% cumulatively. No effect was seen on viremia in infected vaccinated monkeys compared to controls. Protection correlated with the presence of neutralizing antibodies to the challenge viruses tested in peripheral blood mononuclear cells. These data indicate that a vaccine expressing a mismatched Env gene alone can prevent SIV infection in NHPs and identifies an immune correlate that may guide immunogen selection and immune monitoring for clinical efficacy trials.
RV144 试验表明，一种实验性艾滋病疫苗可以预防人类免疫缺陷病毒 1 型（HIV-1）感染。由于其疗效有限，进一步了解预防性艾滋病疫苗的机制仍然是当务之急，而灵长类动物（NHP）的慢病毒感染模型为确定免疫原、载体和免疫相关性提供了机会。在这项研究中，我们表明，用来自猿猴免疫缺陷病毒 SIVmac239 的不匹配 SIV 包膜（Env）基因进行初免-加强免疫接种，可以预防 SIVsmE660 通过直肠内感染。对不同基因初免-加强免疫方案的分析表明，重组腺病毒 5 型（rAd5）初免，然后用复制缺陷型淋巴细胞性脉络丛脑膜炎病毒（rLCMV）加强，可以引发强烈的 CD4 和 CD8 T 细胞和体液免疫反应。这种疫苗在重复粘膜挑战后具有 82%的单次暴露和 62%的累积保护效力，可预防感染。与对照相比，感染疫苗接种的猴子的病毒血症没有影响。保护作用与外周血单核细胞中存在针对挑战病毒的中和抗体有关。这些数据表明，单独表达不匹配 Env 基因的疫苗可以预防 NHP 中的 SIV 感染，并确定了一种免疫相关性，可能指导免疫原选择和免疫监测，以进行临床疗效试验。
