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Antibodies to combat viral infections: development strategies and progress
Nature Reviews Drug Discovery ( IF 120.1 ) Pub Date : 2022-06-20 , DOI: 10.1038/s41573-022-00495-3
Giuseppe Pantaleo 1 , Bruno Correia 2 , Craig Fenwick 1 , Victor S Joo 1 , Laurent Perez 1
Affiliation  

Monoclonal antibodies (mAbs) are appealing as potential therapeutics and prophylactics for viral infections owing to characteristics such as their high specificity and their ability to enhance immune responses. Furthermore, antibody engineering can be used to strengthen effector function and prolong mAb half-life, and advances in structural biology have enabled the selection and optimization of potent neutralizing mAbs through identification of vulnerable regions in viral proteins, which can also be relevant for vaccine design. The COVID-19 pandemic has stimulated extensive efforts to develop neutralizing mAbs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with several mAbs now having received authorization for emergency use, providing not just an important component of strategies to combat COVID-19 but also a boost to efforts to harness mAbs in therapeutic and preventive settings for other infectious diseases. Here, we describe advances in antibody discovery and engineering that have led to the development of mAbs for use against infections caused by viruses including SARS-CoV-2, respiratory syncytial virus (RSV), Ebola virus (EBOV), human cytomegalovirus (HCMV) and influenza. We also discuss the rationale for moving from empirical to structure-guided strategies in vaccine development, based on identifying optimal candidate antigens and vulnerable regions within them that can be targeted by antibodies to result in a strong protective immune response.



中文翻译:

对抗病毒感染的抗体:发展战略与进展

单克隆抗体 (mAb) 作为病毒感染的潜在治疗剂和预防剂具有吸引力,因为它们具有高特异性和增强免疫反应的能力等特点。此外,抗体工程可用于增强效应器功能和延长 mAb 半衰期,结构生物学的进步已通过识别病毒蛋白中的易损区域来选择和优化有效的中和 mAb,这也可能与疫苗设计相关. COVID-19 大流行激发了开发针对严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 的中和 mAb 的广泛努力,目前有几种 mAb 已获得紧急使用授权,不仅提供了对抗 COVID-19 战略的重要组成部分,而且还推动了在其他传染病的治疗和预防环境中利用 mAb 的努力。在这里,我们描述了抗体发现和工程方面的进展,这些进展导致了单克隆抗体的开发,用于对抗由病毒引起的感染,包括 SARS-CoV-2、呼吸道合胞病毒 (RSV)、埃博拉病毒 (EBOV)、人类巨细胞病毒 (HCMV)和流感。我们还讨论了在疫苗开发中从经验策略转向结构指导策略的基本原理,基于确定最佳候选抗原和其中的易受攻击区域,这些区域可以被抗体靶向以产生强烈的保护性免疫反应。我们描述了抗体发现和工程方面的进展,这些进展导致了单克隆抗体的开发,用于对抗由病毒引起的感染,包括 SARS-CoV-2、呼吸道合胞病毒 (RSV)、埃博拉病毒 (EBOV)、人类巨细胞病毒 (HCMV) 和流感. 我们还讨论了在疫苗开发中从经验策略转向结构指导策略的基本原理,基于确定最佳候选抗原和其中的易受攻击区域,这些区域可以被抗体靶向以产生强烈的保护性免疫反应。我们描述了抗体发现和工程方面的进展,这些进展导致了单克隆抗体的开发,用于对抗由病毒引起的感染,包括 SARS-CoV-2、呼吸道合胞病毒 (RSV)、埃博拉病毒 (EBOV)、人类巨细胞病毒 (HCMV) 和流感. 我们还讨论了在疫苗开发中从经验策略转向结构指导策略的基本原理,基于确定最佳候选抗原和其中的易受攻击区域,这些区域可以被抗体靶向以产生强烈的保护性免疫反应。

更新日期:2022-06-20
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