AUTHOR=Federico Lorenzo , Tvedt Tor Henrik Anderson , Gainullin Murat , Osen Julie Røkke , Chaban Viktoriia , Lund Katrine Persgård , Tietze Lisa , Tran Trung The , Lund-Johansen Fridtjof , Kared Hassen , Lind Andreas , Vaage John Torgils , Stratford Richard , Tennøe Simen , Malone Brandon , Clancy Trevor , Myhre Anders Eivind Leren , Gedde-Dahl Tobias , Munthe Ludvig André TITLE=Robust spike-specific CD4+ and CD8+ T cell responses in SARS-CoV-2 vaccinated hematopoietic cell transplantation recipients: a prospective, cohort study JOURNAL=Frontiers in Immunology VOLUME=14 YEAR=2023 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1210899 DOI=10.3389/fimmu.2023.1210899 ISSN=1664-3224 ABSTRACT=

Poor overall survival of hematopoietic stem cell transplantation (HSCT) recipients who developed COVID-19 underlies the importance of SARS-CoV-2 vaccination. Previous studies of vaccine efficacy have reported weak humoral responses but conflicting results on T cell immunity. Here, we have examined the relationship between humoral and T cell response in 48 HSCT recipients who received two doses of Moderna’s mRNA-1273 or Pfizer/BioNTech’s BNT162b2 vaccines. Nearly all HSCT patients had robust T cell immunity regardless of protective humoral responses, with 18/48 (37%, IQR 8.679-5601 BAU/mL) displaying protective IgG anti-receptor binding domain (RBD) levels (>2000 BAU/mL). Flow cytometry analysis of activation induced markers (AIMs) revealed that 90% and 74% of HSCT patients showed reactivity towards immunodominant spike peptides in CD8+ and CD4+ T cells, respectively. The response rate increased to 90% for CD4+ T cells as well when we challenged the cells with a complete set of overlapping peptides spanning the entire spike protein. T cell response was detectable as early as 3 months after transplant, but only CD4+ T cell reactivity correlated with IgG anti-RBD level and time after transplantation. Boosting increased seroconversion rate, while only one patient developed COVID-19 requiring hospitalization. Our data suggest that HSCT recipients with poor serological responses were protected from severe COVID-19 by vaccine-induced T cell responses.