U.S. Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, United States.
Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, United States.
Front Immunol. 2021 Jul 12;12:710044. doi: 10.3389/fimmu.2021.710044. eCollection 2021.
Many broadly neutralizing antibodies (bnAbs) targeting the HIV-1 envelope glycoprotein are being assessed in clinical trials as strategies for HIV-1 prevention, treatment, and antiretroviral-free remission. BnAbs can neutralize HIV-1 and target infected cells for elimination. Concerns about HIV-1 resistance to single bnAbs have led to studies of bnAb combinations with non-overlapping resistance profiles. This review focuses on the potential for bnAbs to induce HIV-1 remission, either alone or in combination with latency reversing agents, therapeutic vaccines or other novel therapeutics. Key topics include preliminary activity of bnAbs in preclinical models and in human studies of HIV-1 remission, clinical trial designs, and antibody design strategies to optimize pharmacokinetics, coverage of rebound-competent virus, and enhancement of cellular immune functions.
许多针对 HIV-1 包膜糖蛋白的广谱中和抗体 (bnAbs) 正在临床试验中作为 HIV-1 预防、治疗和无抗逆转录病毒缓解的策略进行评估。bnAbs 可以中和 HIV-1 并靶向感染细胞进行清除。人们对 HIV-1 对单 bnAbs 的耐药性的担忧导致了对非重叠耐药谱的 bnAb 组合的研究。本综述重点介绍了 bnAbs 单独或与潜伏逆转剂、治疗性疫苗或其他新型治疗药物联合诱导 HIV-1 缓解的潜力。关键主题包括 bnAbs 在临床前模型和 HIV-1 缓解的人体研究中的初步活性、临床试验设计以及优化药代动力学、覆盖反弹病毒、增强细胞免疫功能的抗体设计策略。