Despite the success of Antiretroviral Therapy (ART) in preventing HIV-1-associated clinical progression to AIDS, it is unable to eliminate the viral reservoirs and eradicate the HIV-1 infection. Therapeutic vaccination is an alternative approach to alter the HIV-1 infection course. It can induce effective HIV-1-specific immunity to control viremia and eliminate the need for lifelong ART. Immunological data from spontaneous HIV-1 controllers have shown that cross-reactive T-cell responses are the key immune mechanism in HIV-1 control. Directing these responses toward preferred HIV-1 epitopes is a promising strategy in therapeutic vaccine settings. Designing novel immunogens based on the HIV-1 conserved regions containing a wide range of critical T- and B-cell epitopes of the main viral antigens (conserved multiepitope approaches) supplies broad coverage of global diversity in HIV-1 strains and Human Leukocyte Antigen (HLA) alleles. It can also prevent immune induction to undesirable decoy epitopes theoretically. The efficacy of different novel HIV-1 immunogens based on the conserved and/or functional protective site of HIV-1 proteome has been evaluated in multiple clinical trials. Most of these immunogens were generally safe and able to induce potent HIV-1-specific immunity. However, despite these findings, several candidates have demonstrated limited efficacy in viral replication control. In this study, we used the PubMed and ClinicalTrial.gov databases to review the rationale of designing curative HIV-1 vaccine immunogens based on the conserved favorable site of the virus. Most of these studies evaluate the efficacy of vaccine candidates in combination with other therapeutics and/or with new formulations and immunization protocols. This review briefly describes the design of conserved multiepitope constructs and outlines the results of these vaccine candidates in the recent clinical pipeline.

尽管抗逆转录病毒疗法 (ART) 在预防 HIV-1 相关临床进展为 AIDS 方面取得了成功，但它无法消除病毒库并根除 HIV-1 感染。治疗性疫苗接种是改变 HIV-1 感染过程的另一种方法。它可以诱导有效的 HIV-1 特异性免疫来控制病毒血症并消除终生 ART 的需要。来自自发 HIV-1 控制者的免疫学数据表明，交叉反应性 T 细胞反应是 HIV-1 控制中的关键免疫机制。将这些反应导向首选的 HIV-1 表位是治疗性疫苗设置中的一个有前途的策略。基于包含主要病毒抗原的广泛关键 T 细胞和 B 细胞表位的 HIV-1 保守区域设计新型免疫原（保守的多表位方法）提供了 HIV-1 菌株和人类白细胞抗原的全球多样性的广泛覆盖（ HLA）等位基因。它还可以在理论上防止对不需要的诱饵表位的免疫诱导。基于 HIV-1 蛋白质组的保守和/或功能性保护位点的不同新型 HIV-1 免疫原的功效已在多项临床试验中得到评估。大多数这些免疫原通常是安全的，并且能够诱导有效的 HIV-1 特异性免疫。然而，尽管有这些发现，但一些候选药物在病毒复制控制方面的效果有限。在这项研究中，我们使用了 PubMed 和 ClinicalTrial。gov 数据库，以审查根据病毒的保守有利位点设计治疗性 HIV-1 疫苗免疫原的基本原理。大多数这些研究评估候选疫苗与其他疗法和/或新制剂和免疫方案相结合的功效。本综述简要描述了保守的多表位构建体的设计，并概述了这些候选疫苗在最近的临床管道中的结果。