Vaccine Research Center, National Institute of Allergy and Infectious Disease (NIAID), National Institutes of Health (NIH), Bethesda, Maryland, United States.
Johns Hopkins University, Department of Molecular and Comparative Pathobiology, Baltimore, Maryland, United States.
Curr Opin HIV AIDS. 2022 Jul 1;17(4):247-257. doi: 10.1097/COH.0000000000000742.
Anti-HIV-1 broadly neutralizing antibodies (bNAbs) are promising agents in the fight against the AIDS epidemic. Multiple bNAbs have been already evaluated in clinical trials with encouraging results. This review discusses the use of bNAbs for the prevention and treatment of HIV-1 infection, focusing on manufactured products that have been evaluated in clinical settings.
More than 17 bNAbs have been evaluated for safety and pharmacokinetics in humans. The vast majority presented a well tolerated profile and were generally well tolerated. Serum half-life varied from 12 to 73.5 days and can be improved by the addition of mutations to the Fc regions. Results from the antibody-mediated prevention (AMP) study show that VRC01, a CD4-binding-site bNAb, was effective at preventing the acquisition of sensitive HIV-1 strains but did not prevent the acquisition of strains whose in vitro sensitivity to the antibody had an IC80 of more than 1 μg/ml. New bNAb combinations to improve coverage are currently being evaluated.
In this review, we discuss the current landscape of HIV-1 bNAbs in clinical development. We also present the current strategies employed to improve the breadth, potency, serum half-life, effector function and administration of these compounds.
抗 HIV-1 广谱中和抗体（bNAbs）是对抗艾滋病流行的有前途的药物。已经有多种 bNAbs 在临床试验中进行了评估，结果令人鼓舞。这篇综述讨论了 bNAbs 在 HIV-1 感染的预防和治疗中的应用，重点介绍了已在临床环境中评估的制成产品。
已有 17 多种 bNAbs 已在人体中进行了安全性和药代动力学评估。绝大多数 bNAb 具有良好的耐受性，一般耐受性良好。血清半衰期从 12 天到 73.5 天不等，通过在 Fc 区添加突变可以提高半衰期。抗体介导的预防（AMP）研究的结果表明，VRC01 是一种 CD4 结合位点 bNAb，能有效预防敏感 HIV-1 株的获得，但不能预防对该抗体的体外敏感性 IC80 超过 1μg/ml 的株的获得。目前正在评估新的 bNAb 组合以提高覆盖率。
在这篇综述中，我们讨论了目前处于临床开发阶段的 HIV-1 bNAb 的现状。我们还介绍了目前用于提高这些化合物的广度、效力、血清半衰期、效应功能和给药方式的策略。
