ABSTRACT

With increasing frequency, humans are facing outbreaks of emerging infectious diseases (EIDs) with the potential to cause significant morbidity and mortality. In the most extreme instances, such outbreaks can become pandemics, as we are now witnessing with COVID-19. According to the World Health Organization, this new disease, caused by the novel coronavirus SARS-CoV-2, has already infected more than 10 million people worldwide and led to 499,913 deaths as of 29 June, 2020. How high these numbers will eventually go depends on many factors, including policies on travel and movement, availability of medical support, and, because there is no vaccine or highly effective treatment, the pace of biomedical research. Other than an approved antiviral drug that can be repurposed, monoclonal antibodies (mAbs) hold the most promise for providing a stopgap measure to lessen the impact of an outbreak while vaccines are in development. Technical advances in mAb identification, combined with the flexibility and clinical experience of mAbs in general, make them ideal candidates for rapid deployment. Furthermore, the development of mAb cocktails can provide a faster route to developing a robust medical intervention than searching for a single, outstanding mAb. In addition, mAbs are well-suited for integration into platform technologies for delivery, in which minimal components need to be changed in order to be redirected against a novel pathogen. In particular, utilizing the manufacturing and logistical benefits of DNA-based platform technologies in order to deliver one or more antiviral mAbs has the potential to revolutionize EID responses.

摘要

随着频率的增加，人类正面临新兴传染病（EID）的爆发，这种传染病有可能导致重大发病和死亡。在最极端的情况下，此类暴发可能成为大流行病，正如我们现在在COVID-19上所目睹的那样。根据世界卫生组织的资料，到2020年6月29日，这种由新型冠状病毒SARS-CoV-2引起的新疾病已经感染了全球超过1000万人，并导致499,913人死亡。这些数字最终将上升到何种程度取决于许多因素，包括旅行和出行政策，医疗支持的可获得性，以及由于没有疫苗或高效治疗，生物医学研究的步伐。除了经过批准的可重新利用的抗病毒药物外，单克隆抗体（mAb）最有希望在疫苗研发过程中提供权宜之计，以减少疾病爆发的影响。mAb鉴定的技术进步，加上总体上mAb的灵活性和临床经验，使其成为快速部署的理想选择。此外，mAb混合物的开发可提供比寻求单个出色的mAb更快的途径来开发强大的医学干预措施。此外，mAb非常适合集成到平台技术中进行交付，其中只需更改最少的组件即可针对新型病原体进行重定向。尤其是，