Recombinant BCG-based SARS-CoV-2 vaccine

SummaryThe scale of the humanitarian and economic impact of the COVID-19 pandemic places a high priority on the development of prophylactic and therapeutic countermeasures to better control SARS-CoV-2 infections. Amongthe priorities listed in the NIAID Strategic Plan for COVID-19 research is the need to pursue multiple strategiesto develop a COVID-19 vaccine efficacious across the lifespan, including in the elderly.Recent epidemiologic studies have highlighted the potential for Mycobacterium bovis BCG (the only approvedvaccine for TB prevention) to mitigate through non-specific immunity the prevalence and severity of thesymptoms of COVID-19. Indeed, BCG vaccination has been known since the 1960s to non-specifically improveimmunity against a number of viral pathogens resulting in reduced morbidity and mortality in neonates, childrenand the elderly. Other unique attributes of BCG that make it a vaccine platform of choice for the recombinantexpression of heterologous antigens include the fact that it can produce long-lasting CD4+ and CD8+ T cellresponses, its natural adjuvant properties, its remarkable safety record (> 5 billion doses given to date) and thefact that it is easy and inexpensive to mass-produce.The goal of this project is to leverage ongoing COVID-19 research efforts at Colorado State University togenerate recombinant BCG (rBCG) strains expressing SARS-CoV-2 immunogens (Aim 1) and to assess theimmunogenicity and protective efficacy of rBCG in an established animal challenge model of SARS-CoV-2infection (Aim 2).We hypothesize that the induction of non-specific immunity against SARS-CoV-2 combined with the adaptiveimmune responses elicited by the recombinant expression of validated SARS-CoV-2 antigens will yield rBCG-based COVID-19 vaccines conferring long-lasting protective immunity in people of all ages. Success in thisapproach could rapidly deliver an inexpensive, safe and globally deployable vaccine.