Development and clinical applications of novel antibodies for prevention and treatment of respiratory syncytial virus infection
Development and clinical applications of novel antibodies for prevention and treatment of respiratory syncytial virus infection
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DOI：
10.1016/j.vaccine.2016.09.026
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发表时间：
2017-01-11
期刊：
影响因子：
5.5
通讯作者：
Ramilo, Octavio
中科院分区：
文献类型：
--
作者：
Mejias, Asuncion;Garcia-Maurino, Cristina;Ramilo, Octavio
呼吸道合胞病毒(RSV)仍然是婴幼儿、免疫功能低下患者和老年人发病和死亡的重要原因。尽管疾病负担很高，但缺乏有效和安全的疫苗，尽管目前有几种候选疫苗正在开发中。目前对RSV感染的治疗在很大程度上仍然是支持性的，针对RSV的预防选择仅限于palivizumab。在过去的几年里，出现了包括纳米抗体、多克隆抗体和单抗在内的新的治疗方案，有几种产品正在进行临床前和I、II或III期临床试验。抗病毒药物开发的主要靶点是表面融合(F)糖蛋白，它对病毒的传染性和致病作用至关重要。解决RSV F蛋白的两种构象--融合前和融合后的结构，使RSV的研究发生了革命性的变化。现在已经知道，预输F在诱导中和抗体方面具有很高的优势。在这一部分中，我们将回顾针对RSV的不同抗体的发展阶段和可用性，以预防和治疗急性RSV感染。其中一些新的抗RSV药物已经显示出增强的效力，正在通过替代给药途径进行探索，通过延长半衰期改善了药代动力学曲线，并可能降低设计和制造成本。管理战略不仅需要针对高危人群(包括成人或免疫功能低下的患者)，而且还需要针对以前健康的儿童，事实上，这些儿童代表了大多数因呼吸道合胞病毒感染住院的儿童。对接受纵向治疗的患者进行跟踪治疗对于确定这些策略对急性疾病的影响以及它们对肺部发病率的可能长期益处是至关重要的。(C)2016爱思唯尔有限公司。保留所有权利。
Respiratory syncytial virus (RSV) remains a significant cause of morbidity and mortality in infants and young children, immunocompromised patients and the elderly. Despite the high disease burden, an effective and safe vaccine is lacking, although several candidates are currently in development. Current treatment for RSV infection remains largely supportive and RSV-specific options for prophylaxis are limited to palivizumab. In the past few years, novel therapeutic options including nanobodies, polyclonal and monoclonal antibodies have emerged and there are several products in preclinical and Phase-I, -II or -III clinical trials. The major target for antiviral drug development is the surface fusion (F) glycoprotein, which is crucial for the infectivity and pathogenesis of the virus. Solving the structures of the two conformations of the RSV F protein, the prefusion and postfusion forms, has revolutionized RSV research. It is now known that prefusion F is highly superior in inducing neutralizing antibodies. In this section we will review the stages of development and availability of different antibodies directed against RSV for the prevention and also for treatment of acute RSV infections. Some of these newer anti-RSV agents have shown enhanced potency, are being explored through alternative routes of administration, have improved pharmacokinetic profiles with an extended half-life, and may reduce design and manufacturing costs. Management strategies will require targeting not only high-risk populations (including adults or immunocompromised patients), but also previously healthy children who, in fact, represent the majority of children hospitalized with RSV infection. Following treated patients longitudinally is essential for determining the impact of these strategies on the acute disease as well as their possible long-term benefits on lung morbidity. (C) 2016 Elsevier Ltd. All rights reserved.