Robust spike-specific CD4 + and CD8 + T cell responses in SARS-CoV-2 vaccinated hematopoietic cell transplantation recipients: a prospective, cohort study

• Published in: Frontiers in immunology Vol. 14; p. 1210899
• Main Authors: 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
• Format: Journal Article
• Language: English; Norwegian
• Published: Switzerland Frontiers Media S.A 2023
• Subjects: BNT162 Vaccine; CD4 lymphocyte; CD4-Positive T-Lymphocytes; CD8 lymphocytes; CD8-Positive T-Lymphocytes; Cohort Studies; COVID-19; COVID-19 Vaccines - immunology; Hematopoietic Stem Cell Transplantation; HSCT = hematopoietic stem cell transplant; Humans; Immunoglobulin G; Immunology; Prospective Studies; SARS -CoV -2; vaccine; COVID-19; SARS -CoV -2; vaccine; CD4 lymphocyte; HSCT = hematopoietic stem cell transplant; CD8 lymphocytes
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2023.1210899

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.