Toward a protective Covid-19 vaccine utilizing an established vector platform

摘要 新近出现的冠状病毒SARS-CoV-2，新冠肺炎的病原体，正在中国迅速传播 截至2020年5月16日，世界上有超过480万例病例，32万人死亡。这种新型冠状病毒被认为是 从武汉的一个活体动物市场走出来的中国。它迅速在社区中传播，拥有大量的 人与人之间的传播集群。对几个分离株的测序确定了最接近的 相关毒株是类似SARS的蝙蝠冠状病毒谱系。SARS-CoV-2对抗病毒药物的敏感性 化合物、其在细胞系中复制的能力或调节其复制的宿主因素目前都是未知的。 重要的是，目前还没有治疗这种病毒的疗法，尽管调查研究正在进行中。 对当前疫情的模拟表明，这种病毒可能会感染10亿人，并成为每年一次的 流行病。识别已经产生抗体的人对流行病学和患者都很重要 关心。 随着SARS-CoV-2对全球健康威胁的指数级阐述，迫切需要一种疫苗。 因此，我们建议开发一种新型、高效、安全、规模小的新冠肺炎疫苗 提升潜力。我们的建议使用狂犬病病毒为基础的载体，已被证明是一种有效的疫苗 新出现和再次出现的传染病。我们已经证明了灭活的狂犬病病毒颗粒 含有冠状病毒(CoV)刺突S1蛋白的疫苗可诱导有效的免疫应答并提供保护 对抗中东呼吸综合征冠状病毒(MERS)和严重急性呼吸道综合征的动物系统 呼吸综合征(SARS)冠状病毒，两者都与SARS-CoV-2高度相关。一种类似的疫苗 在此，我们建议分析CoraVax™在小鼠中的免疫原性以及 它在仓鼠模型中的保护能力。

Abstract The recently emerged coronavirus SARS-CoV-2, the causative agent of COVID-19, is rapidly spreading in the world with over 4,8 million cases, and 320,000 deaths as of May 16, 2020. This novel coronavirus is thought to have emerged from a live animal market in Wuhan, China. It has quickly spread in the community with large clusters of human-to-human transmission. Sequencing of several isolates has determined that the most closely related strains are SARS-like bat coronavirus lineages. The susceptibility of SARS-CoV-2 to anti-viral compounds, its ability to replicate in cell lines or host factors regulating its replication are all currently unknown. Importantly, there are no therapeutics available to treat the virus, although investigational studies are underway. Modelling of the current outbreak suggests that the virus could infect >1 billion people and become a yearly epidemic. Identifying people who have developed antibodies is important for the epidemiology as well as patient care. With the exponentially expounding threat of SARS-CoV-2 to global health, a vaccine is desperately needed. Herein we propose the development of a novel, highly efficacious and safe COVID-19 vaccine with facile scale up potential. Our proposal uses a rabies virus-based vector that has proven to be an efficient vaccine against emerging and re-emerging infectious diseases. We have demonstrated that inactivated rabies virus particles containing the coronavirus (CoV) spike S1 protein induce potent immune responses and provide protection in animal systems against Middle Eastern Respiratory Syndrome coronavirus (MERS) and Severe Acute Respiratory Syndrome (SARS) coronavirus, both of which are highly related to SARS-CoV-2. A similar vaccine entitled CoraVax™ is available and herein we propose to analyze CoraVax™ immunogenicity in mice as well as its abilty to protect in a hamster model.