The emergence and re-emergence of highly virulent viral pathogens with the potential to cause a pandemic creates an urgent need for the accelerated discovery of antiviral therapeutics. Antiviral human monoclonal antibodies (mAbs) are promising candidates for the prevention and treatment of severe viral diseases, but their long development timeframes limit their rapid deployment and use. Here, we report the development of an integrated sequence of technologies, including single-cell mRNA-sequence analysis, bioinformatics, synthetic biology and high-throughput functional analysis, that enables the rapid discovery of highly potent antiviral human mAbs, the activity of which we validated in vivo. In a 78-d study modelling the deployment of a rapid response to an outbreak, we isolated more than 100 human mAbs that are specific to Zika virus, assessed their function, identified that 29 of these mAbs have broadly neutralizing activity, and verified the therapeutic potency of the lead candidates in mice and non-human primate models of infection through the delivery of an antibody-encoding mRNA formulation and of the respective IgG antibody. The pipeline provides a roadmap for rapid antibody-discovery programmes against viral pathogens of global concern.

可能导致大流行的高毒力病毒病原体的出现和重新出现迫切需要加速发现抗病毒疗法。抗病毒人单克隆抗体 (mAb) 是预防和治疗严重病毒性疾病的有希望的候选药物，但其较长的开发时间限制了它们的快速部署和使用。在这里，我们报告了一系列综合技术的发展，包括单细胞 mRNA 序列分析、生物信息学、合成生物学和高通量功能分析，这些技术能够快速发现高效抗病毒人类单克隆抗体，我们的活性体内验证。在一项为期 78 天的研究中，模拟了对爆发的快速反应的部署，我们分离了 100 多种针对寨卡病毒的人类单克隆抗体，评估了它们的功能，确定其中 29 种 mAb 具有广泛的中和活性，并通过递送编码抗体的 mRNA 制剂和相应的 IgG 抗体验证了先导候选物在小鼠和非人灵长类动物感染模型中的治疗效力. 该管道为针对全球关注的病毒病原体的快速抗体发现计划提供了路线图。