Anderson Deborah J, Politch Joseph A, Zeitlin Larry, Hiatt Andy, Kadasia Kadryn, Mayer Kenneth H, Ruprecht Ruth M, Villinger Francois, Whaley Kevin J
aDepartments of Obstetrics and Gynecology Boston University School of Medicine, Boston, Massachusetts bMapp Biopharmaceutical, San Diego California cDepartment of Molecular Medicine, Boston University School of Medicine dFenway Health, Harvard Medical School, Boston, Massachusetts eTexas Biomedical Institute, Southwest National Primate Research Center, San Antonio, Texas fNew Iberia Primate Center, New Iberia, Louisiana, USA.
AIDS. 2017 Jul 17;31(11):1505-1517. doi: 10.1097/QAD.0000000000001521.
: Passive immunization, the transfer of antibodies to a nonimmune individual to provide immunological protection, has been used for over 100 years to prevent and treat human infectious diseases. The introduction of techniques to produce human mAbs has revolutionized the field, and a large number of human mAbs have been licensed for the treatment of cancer, autoimmune and inflammatory diseases. With the recent discovery and production of highly potent broadly neutralizing and other multifunctional antibodies to HIV, mAbs are now being considered for HIV therapy and prophylaxis. In this review, we briefly present recent advances in the anti-HIV mAb field and outline strategies for the selection, engineering and production of human mAbs, including the modification of their structure for optimized stability and function. We also describe results from nonhuman primate studies and phase 1 clinical trials that have tested the safety, tolerability, pharmacokinetics, and efficacy of mAb-based HIV prevention strategies, and discuss the future of parenteral and topical mAb administration for the prevention of HIV transmission.
被动免疫，即将抗体转移至非免疫个体以提供免疫保护，已被用于预防和治疗人类传染病长达100多年。生产人源单克隆抗体（mAb）技术的引入彻底改变了这一领域，大量人源mAb已被批准用于治疗癌症、自身免疫性疾病和炎症性疾病。随着最近发现并生产出针对HIV的高效广谱中和及其他多功能抗体，mAb目前正被考虑用于HIV治疗和预防。在本综述中，我们简要介绍抗HIV mAb领域的最新进展，并概述人源mAb的筛选、工程改造和生产策略，包括对其结构进行修饰以优化稳定性和功能。我们还描述了非人灵长类动物研究和1期临床试验的结果，这些研究测试了基于mAb的HIV预防策略的安全性、耐受性、药代动力学和疗效，并讨论了胃肠外和局部应用mAb预防HIV传播的未来。
