Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts, USA.
Massachusetts General Hospital, Infectious Disease Unit, Boston, Massachusetts, USA.
J Infect Dis. 2021 Feb 15;223(12 Suppl 2):22-31. doi: 10.1093/infdis/jiaa165.
Human immunodeficiency virus (HIV) infection leads to the establishment of a long-lived latent cellular reservoir. One strategy to eliminate quiescent reservoir cells is to reactivate virus replication to induce HIV envelope glycoprotein (Env) expression on the cell surface exposing them to subsequent antibody targeting. Via the interactions between the antibody Fc domain and Fc-γ receptors (FcγRs) that are expressed on innate effector cells, such as natural killer cells, monocytes, and neutrophils, antibodies can mediate the elimination of infected cells. Over the last decade, a multitude of human monoclonal antibodies that are broadly neutralizing across many HIV-1 subtypes have been identified and are currently being explored for HIV eradication strategies. Antibody development also includes novel Fc engineering approaches to increase engagement of effector cells and optimize antireservoir efficacy. In this review, we discuss the usefulness of antibodies for HIV eradication approaches specifically focusing on antibody-mediated strategies to target latently infected cells and options to increase antibody efficacy.
人类免疫缺陷病毒(HIV)感染会导致长期潜伏的细胞储库的建立。消除静止储库细胞的一种策略是重新激活病毒复制,诱导 HIV 包膜糖蛋白(Env)在细胞表面表达,使它们随后受到抗体靶向。通过抗体 Fc 结构域与先天效应细胞(如自然杀伤细胞、单核细胞和中性粒细胞)上表达的 Fcγ 受体(FcγRs)之间的相互作用,抗体可以介导感染细胞的清除。在过去的十年中,已经鉴定出多种广泛中和多种 HIV-1 亚型的人源单克隆抗体,目前正在探索用于 HIV 清除策略。抗体的开发还包括新型 Fc 工程方法,以增加效应细胞的参与并优化抗储库效果。在这篇综述中,我们讨论了抗体在 HIV 清除方法中的有用性,特别是针对潜伏感染细胞的抗体介导策略以及提高抗体疗效的选择。