SARS-CoV-2: Pathogenesis and Countermeasure Development

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Since February 2020 we have been mainly working on COVID projects. We have established the Syrian hamster disease model for pathogenesis studies and countermeasure development (Rosenke et al., manuscript in preparation). We have established an in vitro drug screening pipeline that will feed promising candidates into in vivo testing using the Syrian hamster model (Jarvis et al., Antivir Ther 2020; Rosenke et al., J Antimicrobial Chemotherap, submitted). These studies are ongoing. We further assessed the prophylactic/therapeutic efficacy of hydroxychloroquine (HCQ) in two animal disease models. The standard human malaria HCQ prophylaxis and treatment did not significantly benefit clinical outcome nor reduce SARS-CoV-2 replication/shedding in the upper and lower respiratory tract in the rhesus macaque disease model. Similarly, when used for prophylaxis or treatment neither the standard human malaria dose nor a high dose of HCQ had any beneficial effect on clinical disease or SARS-CoV-2 kinetics (replication/shedding) in the Syrian hamster disease model. Results from these two preclinical animal models may prove helpful in guiding clinical use of HCQ for prophylaxis/treatment of COVID-19. Finally, we have rapidly developed repRNA-CoV2S, a stable and highly immunogenic vaccine candidate comprised of an RNA replicon formulated with a novel Lipid InOrganic Nanoparticle (LION) designed to enhance vaccine stability, delivery, and immunogenicity. We have shown that intramuscular injection of LION/repRNA-CoV2S elicited robust anti-SARS-CoV-2 spike protein IgG antibody isotypes indicative of a Type 1 T helper response as well as potent T cell responses in mice. Importantly, a prime-only administration in nonhuman primates elicited antibody responses that potently neutralized SARS-CoV-2 as well as T cell responses indicative of a Type 1 T helper response. These data support further development of LION/repRNA-CoV2S as a vaccine candidate for prophylactic protection from SARS-CoV-2 infection (Erasmus et al., Sci Transl Med 2020). During a regular visit in Mali, our ICER site, in February, we developed and established diagnostic testing for the emerging SARS-CoV-2. At that time Mali did not have any COVID cases, a situation that has changed dramatically. The ICER site (Point G) is now one of 4 national diagnostic centers for COVID testing in Mali.