Department of Pharmacology, Sri Venkateshwaraa Medical College Hospital and Research Centre (SVMCH & RC), Puducherry 605102, India.
Department of Pharmacology, Indira Gandhi Medical College & Research Institute (IGMC & RI), Puducherry 605009, India.
Infect Disord Drug Targets. 2021;21(1):4-27. doi: 10.2174/1871526520666200312154649.
Monoclonal antibodies (mAbs) as alternatives or more often as complementary to the conventional antimicrobials have been developed for the management of infectious conditions for the past two decades. These pharmacotherapeutic strategies are inevitable as the burden of antimicrobial resistance is far-reaching in recent times. MAbs are part of the targeted pharmacotherapy armamentarium with a high degree of specificity - hence, exert comparatively superior efficacy and tolerability than the conventional polyclonal antisera. So far, only five mAbs have been approved for the management of infectious states, since the marketing authorization (1998) given to palivizumab (Synagis®) for the prophylaxis of lower respiratory tract disease caused by a respiratory syncytial virus in pediatric patients. Ibalizumab-uiyk (Trogarzo™) used for the management of multidrug-resistant HIV-1 infection not yielding to at least 10 antiretroviral drugs, was approved recently. Among the three antibacterial mAbs, raxibacumab (ABthrax®/ Anthrin®) and obiltoxaximab (Anthim®) are indicated for the treatment and prophylaxis of inhalation anthrax due to Bacillus anthracis; bezlotoxumab (Zinplava®) is used to reduce the recurrence of Clostridium difficile infection. There are also around 30 and 15 mAbs in different phases of development for viral and bacterial conditions. As alternatives to the traditional antivirals and antibacterials, the antimicrobial mAbs are the need of the hour. These mAbs are more relevant to the management of conditions like emerging viral outbreaks wherein there is a lack of prophylactic vaccines. The current cutting-edge engineering technologies revolutionizing the production of mAbs include phagedisplayed antibody libraries, cloning from single-memory B cells or single-antibody-secreting plasma B cells, proteomics-directed cloning of mAbs from serum clubbed with high-throughput sequencing techniques. Yet, the cost of manufacture continues to be the main limiting factor. In this review, the different therapeutic monoclonal antibodies directed against the microbial pathogens are discussed.
单克隆抗体 (mAbs) 作为传统抗菌药物的替代品或补充剂，在过去二十年中被开发用于治疗感染性疾病。由于近年来抗菌药物耐药性的负担广泛存在，这些药物治疗策略是不可避免的。mAbs 是靶向药物治疗武器库的一部分，具有高度的特异性 - 因此，与传统的多克隆抗血清相比，具有比较优越的疗效和耐受性。迄今为止，只有 5 种 mAbs 被批准用于治疗感染性疾病，因为 palivizumab（Synagis®）于 1998 年获得上市许可，用于预防小儿下呼吸道疾病由呼吸道合胞病毒引起。最近批准了ibalizumab-uiyk（Trogarzo™）用于治疗和预防至少 10 种抗逆转录病毒药物无效的多重耐药 HIV-1 感染。在三种抗细菌 mAbs 中，raxibacumab（ABthrax®/Anthrin®）和 obiltoxaximab（Anthim®）用于治疗和预防因炭疽芽孢杆菌引起的吸入性炭疽；bezlotoxumab（Zinplava®）用于减少艰难梭菌感染的复发。还有大约 30 种和 15 种 mAbs 处于不同的开发阶段，用于治疗病毒和细菌疾病。作为传统抗病毒药物和抗菌药物的替代品，抗菌 mAbs 是当前的需求。这些 mAbs 更适用于治疗新兴病毒爆发等疾病，因为这些疾病缺乏预防性疫苗。当前改变 mAbs 生产的前沿工程技术包括噬菌体展示抗体文库、从单个记忆 B 细胞或单个抗体分泌浆细胞克隆、从与高通量测序技术结合的血清中定向克隆 mAbs 的蛋白质组学。然而，制造成本仍然是主要的限制因素。在这篇综述中，讨论了针对微生物病原体的不同治疗性单克隆抗体。
