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Principal Investigator: Michael Grigg
Organization: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
Fiscal Year: 2020
Award: $83,030
Funding agency: National Institute of Allergy and Infectious Diseases
Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), the etiologic agent of COVID-19, emerged in 2019 as a public health emergency and global pandemic. SARS-CoV-2 is a linear, non-segmented, capped, polyadenylated positive-sense, single stranded RNA virus related to SARS-CoV and MERS-CoV, two other deadly respiratory coronaviruses that caused human epidemics in 2002 and 2012, respectively. Beta-Coronaviruses evolve diversity by accumulating spontaneous mutations (genetic drift) and by recombination (admixing genome segments of different ancestry). SARS-CoV (also known as beta-CoV) is a mosaic of alpha and gamma-CoV lineages and is thought to have evolved by recombination between mammalian-like and avian-like parent viruses. Likewise, surveillance studies of the MERS-CoV epidemic established that the origin of the 2015 human outbreak strain was generated by recombination among different MERS-CoV lineages co-circulating in dromedary camels in Saudi Arabia in 2014. Our proposal will determine the genome-scale evolutionary dynamics of SARS-CoV-2 by visualizing multiple evolutionary relationships to understand the role of recombination in the emergence and genetic origin of the current population genetic structure of SARS-CoV-2. The Molecular Parasitology Section (LPD, NIAID) has extensive experience conducting population genomic studies and is vested in both the knowledge and techniques to adapt the current methodology we use to study haploid eukaryotic genomes to haploid, non-segmented RNA virus genomes. Furthermore, we are pursuing an active vaccine program by co-expressing parasite surface antigens in virus-like particles (VLPs) as part of our oral vaccine effort to generate protective, neutralizing antibodies and strong mucosal immunity against protozoan parasites. Our plan is to adapt (effectively re-purpose) this methodology to generate immunity against SARS-CoV-2 spike and N proteins. Our vaccine initiative represents one of the few programs involved in generating an effective oral vaccine against respiratory viruses that cause COVID-19.
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