Countermeasures against COVID-19

该实验室开发了两种单独表达SARS-CoV-2刺突蛋白或与埃博拉病毒糖蛋白（EBOV GP）联合表达的候选疫苗。研究表明，鼻内或肌内（IM）接种单剂量疫苗可保护动物在SARS-CoV-2攻击后免受疾病。当我们在SARS-CoV-2攻击前10天用单剂量的VSV-SARS 2-EBOV疫苗接种恒河猴时，只有通过IM途径接种的动物没有显示出COVID-19的迹象，而IN接种的动物确实包括肺部病变（Furuyama et al.，未公布的数据）。 我们与Munsters病毒生态学部门一起，使用基于VSV的伪粒子系统研究了β-冠状病毒的受体使用。我们发现SARS-CoV-2使用ACE 2作为进入细胞的受体（Letko等人，Nature Microbiology 2020）。此外，我们与Munster博士合作建立了SARS-CoV-2的小鼠模型，以便能够测试抗病毒药物和疫苗（Yinda等人，2020; PMID 32803199）。 为了扩大我们对COVID-19期间人类细胞因子反应的理解，我们正在分析从印第安纳州患者中收集的人类血清样本。此外，我们正在确定这些样品中对SARS-CoV-2的IgG应答，并正在研究这些样品中抗体依赖性感染增强的潜力（Shifflett，Furuyama等人，未公布的数据）。 最后，TLR 4和TLR 7/8激动剂已经显示出作为针对流感病毒感染的治疗是有益的。此外，TLR 7/8已被证明在SARS-CoV-1感染和发病机制中发挥作用。因此，我们正在测试这两种激动剂作为啮齿动物中SARS-CoV-2感染的潜在治疗方法。该项目处于非常早期的阶段。

The lab developed 2 vaccine candidates expressing the SARS-CoV-2 spike protein alone or in combination with the Ebola virus glycoprotein (EBOV GP). Hamster studies revealed that a single dose of either vaccine administered intranasally or intramuscularly (IM) protected the animals from disease after SARS-CoV-2 challenge. When we vaccinated rhesus macaques 10 days prior to SARS-CoV-2 challenge with a single dose of the VSV-SARS2-EBOV vaccine, only animals vaccinated by the IM route showed no signs of COVID-19, whereas the IN vaccinated animals did including lung lesions (Furuyama et al., unpublished data). Together with Dr. Munsters Virus Ecology Section, we studied the receptor usage of beta-coronaviruses using a VSV-based pseudoparticle system. We found that SARS-CoV-2 uses ACE2 as an entry receptor into cells (Letko et al., Nature Microbiology 2020). Furthermore, we collaborated with Dr. Munster on the establishment of a mouse model for SARS-CoV-2 in order to be able to test antivirals and vaccines (Yinda et al., 2020; PMID 32803199). In order to expand our understanding of human cytokine responses during COVID-19, we are analyzing human serum samples collected over time from patients from Indiana. In addition, we are determining IgG responses to SARS-CoV-2 in these samples and are looking into the potential of antibody-dependent enhancement of infection in these samples (Shifflett, Furuyama et al., unpublished data). Lastly, TLR4 and TLR7/8 agonists have shown to be beneficial as a treatment against influenza virus infections. In addition, TLR7/8 have been demonstrated to play a role in SARS-CoV-1 infection and pathogenesis. Therefore, we are testing both agonists as a potential treatment against SARS-CoV-2 infections in rodents. This project is in very early stages.