Viral diversity and immune escape variants in vulnerable individuals post-vaccination.

Emerging viral variants are burgeoning rapidly in this COVID-19 pandemic. However, a number of critical questions remain unanswered and require a rapid response to influence public health decisions, to prevent subsequent pandemic waves, and to reduce their impacts. Are all variants of public health concern? Which variants acquire the capability to evade vaccine-induced protection and re-infect vaccinated individuals? Does the age or the immune status of the individual influence the evolution and transmission of variants, particularly vaccination? To address these essential and urgent questions, our multi-disciplinary team of researchers will actively investigate new infections in previously vaccinated individuals in the general population, as well as among defined cohorts of patients of elderly and cancer patients. We will intently probe for the emergence of novel SARS-CoV-2 variants in these post-vaccination populations and assess their impact on human health through viral genomics, computational biology, and immune testing. Our proposal rests on 3 major thematic pillars: A.Clinical surveillance of SARS-CoV-2 variants in human cohorts. We are exploiting novel sequencing technologies for rapid variant detection through viral genomics in defined human cohorts. B.Viral genome analysis. We will sequence viral genome from this cohort and track mutations both within and between patients. We will put these genomes in the phylogenetic context of global and pan-Canadian genome databases to infer transmission events of variants into and out of elderly and immunocompromised individuals. C.Immunological and functional evaluation of SARS-CoV-2 variants. Modelling of mutated viral proteins will predict their impact on epitope diversity/antigenicity, cellular and humoral immunity, and serological detection. We will model the future transmission of SARS-CoV-2 to identify optimal control scenarios where the effectiveness of available vaccines is reduced.