Countermeasures against COVID-19

实验室开发了单独表达SARS-CoV-2刺突蛋白或与埃博拉病毒糖蛋白（EBOV GP）联合表达的2种候选疫苗。对仓鼠的研究表明，在SARS-CoV-2攻击后，单剂量鼻内或肌肉注射（IM）疫苗可保护动物免受疾病的侵害。当我们在SARS-CoV-2攻击前10天给恒河猴接种单剂量VSV-SARS2-EBOV疫苗时，只有通过IM途径接种的动物没有出现COVID-19的迹象，而接种IN疫苗的动物则出现了肺部病变（Furuyama等人，未发表的数据）。

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IM route showed no signs of COVID-19, whereas the IN vaccinated animals did including lung lesions (Furuyama et al., unpublished data).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looking into the potential of antibody-dependent enhancement of infection in these samples (Shifflett, Furuyama et al., unpublished data).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.