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Principal Investigator: Heinrich Feldmann
Organization: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
Fiscal Year: 2020
Award: $2,585,920
Funding agency: National Institute of Allergy and Infectious Diseases
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.
Terms: <2019 novel coronavirus><2019-nCoV><7S Gamma Globulin><Acute><Animal Disease Models><Animal Model><Animal Models and Related Studies><Antibodies><Antibody Response><Antiviral Agents><Antiviral Drugs><Antivirals><COVID><COVID-19><COVID19><Clinical><CoV disease><Containment><Data><Development><Diagnostic><Diagnostic tests><Disease><Disease model><Disorder><Dose><Drug Screening><Dysfunction><Emerging Communicable Diseases><Emerging Infectious Diseases><Fostering><Functional disorder><Goals><Golden Hamsters><Golden Syrian Hamsters><Human><Hydroxychlorochin><Hydroxychloroquine><IgG><Immune response><Immunoglobulin G><Immunological response><In Vitro><Infection><International><Intramuscular Injections><Kinetics><Lipids><Lower respiratory tract structure><Lung diseases><M mulatta><M. mulatta><Macaca mulatta><Malaria><Mali><Manuscripts><Mesocricetus auratus><Mice><Mice Mammals><Modeling><Modern Man><Murine><Mus><NIAID><NIH><National Institute of Allergy and Infectious Disease><National Institutes of Health><Non-Polyadenylated RNA><Outcome><Oxychlorochin><Oxychloroquine><Paludism><Pathogenesis><Pathogenicity><Physiopathology><Plasmodium Infections><Preparation><Prophylactic treatment><Prophylaxis><Proteins><Public Health><Pulmonary Diseases><Pulmonary Disorder><RNA><RNA Gene Products><Replication Unit><Replicon><Research><Respiratory Disease><Respiratory System Disease><Respiratory System Disorder><Rhesus Macaque><Rhesus Monkey><Ribonucleic Acid><SARS-CoV-2><SARS-CoV2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related coronavirus 2><Severe acute respiratory syndrome coronavirus 2><Site><Syrian Hamsters><T cell response><Testing><Therapeutic><Time><Treatment Efficacy><United States National Institutes of Health><Vaccines><Viral><Viral Diseases><Virus><Virus Diseases><Visit><Wuhan coronavirus><anti-microbial><anti-viral agents><anti-viral drugs><anti-virals><antimicrobial><communicable disease transmission><corona virus disease><corona virus disease 2019><coronavirus disease><coronavirus disease 2019><design><designing><developmental><disease of the lung><disease transmission><disorder model><disorder of the lung><host response><immunogenic><immunogenicity><immunoresponse><in vivo evaluation><in vivo testing><infectious disease transmission><innovate><innovation><innovative><intervention efficacy><intramuscular drug administration><lower respiratory tract><lung disorder><model of animal><model organism><nano particle><nano-sized particle><nanoparticle><nanosized particle><non-human primate><nonhuman primate><novel><pathogenic virus><pathophysiology><pre-clinical><preclinical><prophylactic><response><therapeutic efficacy><therapeutically effective><therapy efficacy><vaccine candidate><viral infection><viral pathogen><virus infection><virus-induced disease>