Frontiers in Immunology (Jul 2023)

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

  • Lorenzo Federico,
  • Lorenzo Federico,
  • Tor Henrik Anderson Tvedt,
  • Murat Gainullin,
  • Murat Gainullin,
  • Julie Røkke Osen,
  • Julie Røkke Osen,
  • Viktoriia Chaban,
  • Viktoriia Chaban,
  • Katrine Persgård Lund,
  • Katrine Persgård Lund,
  • Lisa Tietze,
  • Lisa Tietze,
  • Trung The Tran,
  • Trung The Tran,
  • Fridtjof Lund-Johansen,
  • Fridtjof Lund-Johansen,
  • Hassen Kared,
  • Hassen Kared,
  • Andreas Lind,
  • John Torgils Vaage,
  • John Torgils Vaage,
  • Richard Stratford,
  • Simen Tennøe,
  • Brandon Malone,
  • Trevor Clancy,
  • Anders Eivind Leren Myhre,
  • Anders Eivind Leren Myhre,
  • Tobias Gedde-Dahl,
  • Ludvig André Munthe,
  • Ludvig André Munthe

DOI
https://doi.org/10.3389/fimmu.2023.1210899
Journal volume & issue
Vol. 14

Abstract

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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.

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