Characterising cross-reactive and durable immunity to SARS-CoV-2

The SARS-CoV-2 pandemic has swept the world and poses a significant global threat to lives and livelihoods. South Africa leads the African continent in confirmed case numbers. This proposal seeks to contribute to the African response to the COVID-19 epidemic by generating new knowledge regarding immunity to SARS-CoV-2 in South Africans. We will examine both pre-existing immune responses in uninfected individuals, resulting from prior infection with genetically-related circulating non-SARS coronaviruses, as well as memory responses that develop after recovery from COVID-19. The aim of this research is to determine whether these pre-existing responses influence clinical outcome and immune memory. We will also develop tools for assessing immune responses to SARS-CoV-2, and apply these to define detailed antibody signatures and kinetics, memory B cell responses and CD4+ T cell help and CD8+ T cell antiviral responses, to SARS-CoV-2. These studies will be performed in a cohort of healthcare workers, who represent a high risk group for both exposure and potential reinfection, and where understanding protective immunity and its duration is critical. These studies will provide a greater understanding of the nature of immune responses to SARSCoV- 2 in our population, which represents important baseline information for interpreting vaccine responses in African populations. Ultimately, these studies will contribute to regional efforts to understand the immune response to COVID-19 in Africans, and pave the way for interventions such as vaccines to control the pandemic.