流感中抗体依赖增强作用可能性的结构与数学建模分析
A Structural and Mathematical Modeling Analysis of the Likelihood of Antibody-Dependent Enhancement in Influenza.
作者信息
Ramakrishnan Boopathy, Viswanathan Karthik, Tharakaraman Kannan, Dančík Vlado, Raman Rahul, Babcock Gregory J, Shriver Zachary, Sasisekharan Ram
机构信息
Visterra, Inc. One Kendall Square, Suite B3301, Cambridge, MA 02139, USA.
Department of Biological Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 01890, USA.
出版信息
Trends Microbiol. 2016 Dec;24(12):933-943. doi: 10.1016/j.tim.2016.09.003. Epub 2016 Oct 14.
Abstract
Broadly neutralizing monoclonal antibodies (bNAbs) for viral infections, such as HIV, respiratory syncytial virus (RSV), and influenza, are increasingly entering clinical development. For influenza, most neutralizing antibodies target influenza virus hemagglutinin. These bNAbs represent an emerging, promising modality for treatment and prophylaxis of influenza due to their multiple mechanisms of antiviral action and generally safe profile. Preclinical work in other viral diseases, such as dengue, has demonstrated the potential for antibody-based therapies to enhance viral uptake, leading to enhanced viremia and worsening of disease. This phenomenon is referred to as antibody-dependent enhancement (ADE). In the context of influenza, ADE has been used to explain several preclinical and clinical phenomena. Using structural and viral kinetics modeling, we assess the role of ADE in the treatment of influenza with a bNAb.
摘要
针对病毒感染（如HIV、呼吸道合胞病毒（RSV）和流感）的广泛中和单克隆抗体（bNAb）正越来越多地进入临床开发阶段。对于流感而言，大多数中和抗体靶向流感病毒血凝素。这些bNAb由于其多种抗病毒作用机制和总体安全的特性，代表了一种新兴的、有前景的流感治疗和预防方法。在登革热等其他病毒性疾病中的临床前研究表明，基于抗体的疗法有增强病毒摄取的可能性，从而导致病毒血症增强和病情恶化。这种现象被称为抗体依赖增强（ADE）。在流感的背景下，ADE已被用于解释几种临床前和临床现象。我们使用结构和病毒动力学模型，评估ADE在使用bNAb治疗流感中的作用。
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