HIVACAT T-cell immunogen (HTI) is a novel human immunodeficiency virus (HIV) vaccine immunogen designed to elicit cellular immune responses to HIV targets associated with viral control in humans. The AELIX-002 trial was a randomized, placebo-controlled trial to evaluate as a primary objective the safety of a combination of DNA.HTI (D), MVA.HTI (M) and ChAdOx1.HTI (C) vaccines in 45 early-antiretroviral (ART)-treated individuals (44 men, 1 woman; NCT03204617). Secondary objectives included T-cell immunogenicity, the effect on viral rebound and the safety of an antiretroviral treatment interruption (ATI). Adverse events were mostly mild and transient. No related serious adverse events were observed. We show here that HTI vaccines were able to induce strong, polyfunctional and broad CD4 and CD8 T-cell responses. All participants experienced detectable viral rebound during ATI, and resumed ART when plasma HIV-1 viral load reached either >100,000 copies ml⁻¹, >10,000 copies ml⁻¹ for eight consecutive weeks, or after 24 weeks of ATI. In post-hoc analyses, HTI vaccines were associated with a prolonged time off ART in vaccinees without beneficial HLA (human leukocyte antigen) class I alleles. Plasma viral load at the end of ATI and time off ART positively correlated with vaccine-induced HTI-specific T-cell responses at ART cessation. Despite limited efficacy of the vaccines in preventing viral rebound, their ability to elicit robust T-cell responses towards HTI may be beneficial in combination cure strategies, which are currently being tested in clinical trials.

HIVACAT T 细胞免疫原 (HTI) 是一种新型人类免疫缺陷病毒 (HIV) 疫苗免疫原，旨在引发与人类病毒控制相关的 HIV 靶点的细胞免疫反应。AELIX-002 试验是一项随机、安慰剂对照试验，以评估 DNA.HTI (D)、MVA.HTI (M) 和 ChAdOx1.HTI (C) 疫苗组合在 45 名早期-抗逆转录病毒 (ART) 治疗的个体（44 名男性，1 名女性；NCT03204617）。次要目标包括 T 细胞免疫原性、对病毒反弹的影响和抗逆转录病毒治疗中断 (ATI) 的安全性。不良事件大多是轻微和短暂的。没有观察到相关的严重不良事件。我们在此表明​​，HTI 疫苗能够诱导强烈、多功能和广泛的 CD4 和 CD8 T 细胞反应。^-1 , >10,000 copies ml ^-1连续八周，或在ATI 24周后。在事后分析中，HTI 疫苗与没有有益 HLA（人类白细胞抗原）I 类等位基因的疫苗接种者停用 ART 的时间延长有关。ATI 结束时的血浆病毒载量和停止 ART 时的血浆病毒载量与 ART 停止时疫苗诱导的 HTI 特异性 T 细胞反应呈正相关。尽管疫苗在预防病毒反弹方面的功效有限，但它们引发针对 HTI 的强大 T 细胞反应的能力可能有利于联合治疗策略，目前正在临床试验中进行测试。