Roles of fragment crystallizable-mediated effector functions in broadly neutralizing antibody activity against HIV.
Roles of fragment crystallizable-mediated effector functions in broadly neutralizing antibody activity against HIV.
复制标题
碎片可结晶介导的效应子功能在广泛中和抗HIV的抗体活性中的作用。
DOI：
10.1097/coh.0000000000000644
复制
发表时间：
2020-09
影响因子：
4.1
通讯作者：
Brad Jones R
中科院分区：
文献类型：
--
作者：
Danesh A;Ren Y;Brad Jones R
“广谱中和抗体”(BNAbs)是一种罕见的HIV特异性抗体，显示出有效中和各种病毒分离株的非典型能力。虽然通过接种疫苗获得bNAb的努力尚未成功，但近年来针对艾滋病毒预防和治疗的被动免疫方法在临床前和临床上取得了显著进展。在此，我们将重点放在这一成功的基础上，超越中和，通过Fc-效应器功能，进一步利用抗体可用的各种效应器功能。最近的研究利用设计bNAb Fc结构域的能力来增强或取消特定的效应器功能，以证明抗体依赖的细胞介导的细胞毒性等活动在体内对抗病毒活性有很大贡献。有趣的是，最近在非人类灵长类动物和人类中的研究表明，被动的bNAb输注可以通过“疫苗效应”增强病毒特异性T细胞反应，从而导致持久免疫。旨在增强效应器功能的抗体工程策略与bNAbs广泛而有效的抗原识别谱相结合，有可能产生强大的HIV新疗法。我们的目标是及时回顾最近的进展，以催化这一发展。
‘Broadly neutralizing antibodies’ (bNAbs), are rare HIV-specific antibodies which exhibit the atypical ability to potently neutralize diverse viral isolates. While efforts to elicit bNAbs through vaccination have yet to succeed, recent years have seen remarkable pre-clinical and clinical advancements of passive immunization approaches targeting both HIV prevention and cure. We focus here on the potential to build upon this success by moving beyond neutralization to additionally harness the diverse effector functionalities available to antibodies via Fc-effector functions. Recent studies have leveraged the ability to engineer bNAb Fc domains to either enhance or abrogate particular effector functions to demonstrate that activities such as antibody dependent cell-mediated cytotoxicity contribute substantially to in vivo antiviral activity. Intriguingly, recent studies in both non-human primates and in humans have suggested that passive bNAb infusion can lead to durable immunity by enhancing virus-specific T-cell responses through a ‘vaccinal effect’. The combination of antibody engineering strategies designed to enhance effector functions, with the broad and potent antigen recognition profile of bNAbs, has the potential to give rise to powerful new therapeutics for HIV. We aim to provide a timely review of recent advances to catalyze this development.