Adaptive responses to SARS-CoV-2 variants in the context of hybrid immunity and immune impairment

SARS-CoV-2 evolved variants that could escape previous immunity and transmit better. This process so far culminated in the Omicron variant, which led to a global infection wave of unprecedented scale. To ensure an effective response to variants, their biology, evolution, and mechanisms of escape must be better understood. It is critical to rapidly determine cross-protection afforded by vaccination or previous infections against emerging variants and understand the mechanisms for that protection or lack thereof. This will require understanding B and T cell targets, as well as how these relate to emerging variation, to quickly model/predict new viral escape mutations. Such a high- resolution response is only possible by combining immunology, virology, T and B cell biology, antibody mapping, and structural biology, and will need to be done for increasingly hybrid-induced immunity. The effort must also benefit young investigators. Specific Aims 1. Perform immunological surveillance of current and emerging variants and predict future mutations which impact antibody and T cell immunity 2. Determine how increasingly complex hybrid immunity functions against current and emerging variants 3. Determine how immune impairment mediated by co-infection with HIV modulates response to variants 4. Promote the next generation of African scientists through cutting- edge research and scientific exchange