Grant: Op. Gr: Emer. COVID Res. Gaps/Prior- Dif. Impacts on Hist. Excl/Underserved Pops

The COVID-19 pandemic has presented an unprecedented challenge to Canada. To date, >1.5 million Canadians have been infected with the SARS-CoV-2 virus, and >27,000 individuals have died. The impact is even greater in kidney transplant recipients (KTR), often including members of ethnocultural, Indigenous, marginalized communities, with incidence exceeding that of the general population by 15-fold, and risk of death also higher. Differences between KTR and the general population have been attributed to immunosuppression geared towards attenuating the immune response and thus prevent rejection. The immunosuppressed state contributes to markedly lower neutralizing antibody responses to SARS-CoV-2 vaccines in KTR, which may still be offering protection; however, vaccine-induced anti-HLA antibody development, may increase risk of graft rejection and loss. Immune response to vaccines, viruses, and donor specific proteins (HLA) by KTRs' sex and age, with young females generating greater innate and adaptive immune responses than males. Our study will utilize longitudinally collected biospecimens from the MUHC Kidney Disease Biorepository. We will ascertain donor and recipient HLA genotypes by next generation sequencing, and anti-HLA antibodies - by solid phase assays. Using high-resolution genomic technologies, we will study the molecular makeup of blood immune cells and their activity. Simultaneous profiling of variation in genomic sequence of receptors on immune cells will allow us to identify expansion of antibody forming cells and their relative distribution before and after vaccination. We will evaluate desirable as well as undesirable antibody responses to mRNA SARS-CoV-2 vaccines and how they are modified by timing, dose, and vaccine product, as well as KTRs' age and sex. This work will offer solutions towards the prevention of SARS-CoV-2 infection and decrease risk of graft rejection through personalized management of vulnerable KTR.