HLA-DP diversity is associated with improved response to SARS-Cov-2 vaccine in hematopoietic stem cell transplant recipients

Abstract

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients show lower humoral vaccine responsiveness than immunocompetent individuals. HLA diversity, measured by the HLA evolutionary divergence (HED) metrics, reflects the diversity of the antigenic repertoire presented to Tcells, and has been shown to predict response to cancer immunotherapy. We retrospectively investigated the association of HED with humoral response to SARS-CoV-2 vaccine in allo-HSCT recipients. HED was calculated as pairwise genetic distance between alleles at HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 loci in recipients and their donors. Low anti-spike IgG levels (<30 BAU/mL) were associated with short time from allo-SCT and low donor DPB1-HED, mostly related to donor DPB1 homozygosity. The diversity of donor HLA-DP molecules, assessed by heterozygosity or sequence divergence, may thus impact the efficacy of donor-derived CD4 Tcells to sustain vaccine-mediated antibody response in allo-HSCT recipients.