Botnar Research Centre, University of Oxford, Oxford, UK.
Eli Lilly and Company, Indianapolis, IN, USA.
Nat Rev Immunol. 2021 Jun;21(6):382-393. doi: 10.1038/s41577-021-00542-x. Epub 2021 Apr 19.
Several neutralizing monoclonal antibodies (mAbs) to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed and are now under evaluation in clinical trials. With the US Food and Drug Administration recently granting emergency use authorizations for neutralizing mAbs in non-hospitalized patients with mild-to-moderate COVID-19, there is an urgent need to discuss the broader potential of these novel therapies and to develop strategies to deploy them effectively in clinical practice, given limited initial availability. Here, we review the precedent for passive immunization and lessons learned from using antibody therapies for viral infections such as respiratory syncytial virus, Ebola virus and SARS-CoV infections. We then focus on the deployment of convalescent plasma and neutralizing mAbs for treatment of SARS-CoV-2. We review specific clinical questions, including the rationale for stratification of patients, potential biomarkers, known risk factors and temporal considerations for optimal clinical use. To answer these questions, there is a need to understand factors such as the kinetics of viral load and its correlation with clinical outcomes, endogenous antibody responses, pharmacokinetic properties of neutralizing mAbs and the potential benefit of combining antibodies to defend against emerging viral variants.
已经开发出几种针对严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 的中和单克隆抗体 (mAb)，目前正在临床试验中进行评估。随着美国食品和药物管理局最近批准将中和单克隆抗体用于非住院的 COVID-19 轻症至中度患者，鉴于最初供应有限，迫切需要讨论这些新型疗法的更广泛潜力，并制定在临床实践中有效部署它们的策略。在这里，我们回顾了被动免疫的先例，并从使用针对呼吸道合胞病毒、埃博拉病毒和 SARS-CoV 感染等病毒感染的抗体疗法中吸取了经验教训。然后，我们专注于使用恢复期血浆和中和单克隆抗体治疗 SARS-CoV-2。我们回顾了具体的临床问题，包括患者分层的理由、潜在的生物标志物、已知的风险因素以及最佳临床使用的时间考虑因素。为了回答这些问题，需要了解病毒载量的动力学及其与临床结果的相关性、内源性抗体反应、中和单克隆抗体的药代动力学特性以及结合抗体以抵御新兴病毒变体的潜在益处等因素。
