A perspective on potential antibody-dependent enhancement of SARS-CoV-2
A perspective on potential antibody-dependent enhancement of SARS-CoV-2
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DOI：
10.1038/s41586-020-2538-8
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发表时间：
2020-07-13
期刊：
影响因子：
64.8
通讯作者：
Virgin, Herbert W.
中科院分区：
文献类型：
--
作者：
Arvin, Ann M.;Fink, Katja;Virgin, Herbert W.
本文综述了抗体依赖增强对SARS-CoV-2感染预防和治疗的影响。抗体依赖增强(ADE)是疫苗和抗体疗法发展的一个普遍关注的问题，因为任何病毒的抗体保护机制都有可能放大感染或引发有害的免疫病理学。这种可能性需要在2019年冠状病毒病(新冠肺炎)大流行的这个关键时刻仔细考虑，这种疾病是由严重急性呼吸综合征冠状病毒2号(SARS-CoV-2)引起的。在这里，我们回顾了与疾病ADE风险相关的观察结果，以及它们对SARS-CoV-2感染的潜在影响。目前，还没有已知的临床结果、免疫学分析或生物标志物可以区分任何严重的病毒感染和免疫增强性疾病，无论是通过检测抗体、T细胞还是固有的宿主反应。在体外系统和动物模型无法预测疾病的ADE风险，部分原因是保护性和潜在有害的抗体介导机制是相同的，设计动物模型取决于了解抗病毒宿主反应可能如何对人类有害。我们缺乏知识的影响是双重的。首先，迫切需要进行全面的研究，以确定SARS-CoV-2保护性免疫的临床相关性。其次，由于无论是接种疫苗还是抗体治疗后，都无法可靠地预测疾病的ADE--无论致病的是什么病毒--随着新冠肺炎免疫干预措施的发展，仔细分析人类的安全性将是至关重要的。
The antibody-dependent enhancement of disease is reviewed, with an emphasis on implications for the prevention and treatment of SARS-CoV-2 infection.Antibody-dependent enhancement (ADE) of disease is a general concern for the development of vaccines and antibody therapies because the mechanisms that underlie antibody protection against any virus have a theoretical potential to amplify the infection or trigger harmful immunopathology. This possibility requires careful consideration at this critical point in the pandemic of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we review observations relevant to the risks of ADE of disease, and their potential implications for SARS-CoV-2 infection. At present, there are no known clinical findings, immunological assays or biomarkers that can differentiate any severe viral infection from immune-enhanced disease, whether by measuring antibodies, T cells or intrinsic host responses. In vitro systems and animal models do not predict the risk of ADE of disease, in part because protective and potentially detrimental antibody-mediated mechanisms are the same and designing animal models depends on understanding how antiviral host responses may become harmful in humans. The implications of our lack of knowledge are twofold. First, comprehensive studies are urgently needed to define clinical correlates of protective immunity against SARS-CoV-2. Second, because ADE of disease cannot be reliably predicted after either vaccination or treatment with antibodies-regardless of what virus is the causative agent-it will be essential to depend on careful analysis of safety in humans as immune interventions for COVID-19 move forward.