Characterization of first- and second-generation RNA vaccine immunogenicity against SARS-CoV-2 variants of concern in Canada

RNA vaccines enabled the fastest response to the COVID-19 pandemic. However, it is not yet well-understood how first-generation vaccines made with the wild type spike antigen are able to act against SARS-CoV-2 variants of concern (VOC). Furthermore, second-generation COVID-19 vaccines are now in development in order to minimize the dose of RNA required and limit the associated side effects. The first Canada-made RNA vaccine is currently being tested in a Phase I clinical trial, which uses self-amplifying RNA (saRNA) and is produced by Precision NanoSystems Inc. (PNI). saRNA is a special type of messenger RNA (mRNA) which is able to replicate itself in a patient's cells. However, it is not yet defined how these different types of vaccines, including first-generation mRNA and second-generation saRNA COVID-19 vaccines, affect how long the immune response lasts. Furthermore, a marginalized group of patients have exhibited severe anaphylactic reactions to the RNA vaccines, which may be in part due to a sensitivity to one of the lipid components called poly(ethylene glycol) (PEG). In order to fill these research gaps, we will characterize the functionality of first-generation mRNA vaccines against SARS-CoV-2 VOC in Canada in collaboration with the Snutch laboratory at UBC, who leads the surveillance of mutations through the CanCOGeN-VirusSeq initiative. Then, we will investigate how the duration of immunity induced by mRNA and saRNA COVID-19 vaccines. Finally, we will identify whether RNA vaccine formulations without PEG are able to induce an equivalent immune response in collaboration with the Cullis lab at UBC. The results of this research will inform the activity against SARS-CoV-2 VOC for current and future COVID-19 vaccine candidates available in Canada. These studies will also generate knowledge regarding design of RNA vaccines, including the necessity of the PEG component, both for the ongoing COVID-19 pandemic and for future outbreaks.