Deficiency of SARS-CoV-2 T-cell responses after vaccination in long-term allo-HSCT survivors translates into abated humoral immunity
Journal article, 2022
Recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT) for hematological diseases are at risk of severe disease and death from COVID-19. To determine the safety and immunogenicity of BNT162b2 and mRNA-1273 COVID-19 vaccines, samples from 50 infection-naive allo-HSCT recipients (median, 92 months from transplantation, range, 7-340 months) and 39 healthy controls were analyzed for serum immunoglobulin G (IgG) against the receptor binding domain (RBD) within spike 1 (S1) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; anti–RBD-S1 IgG) and for SARS-CoV-2–specific T-cell immunity, reflected by induction of T-cell–derived interferon-g in whole blood stimulated ex vivo with 15-mer SI-spanning peptides with 11 amino acid overlap S1-spanning peptides. The rate of seroconversion was not significantly lower in allo-transplanted patients than in controls with 24% (12/50) and 6% (3/50) of patients remaining seronegative after the first and second vaccination, respectively. However, 58% of transplanted patients lacked T-cell responses against S1 peptides after 1 vaccination compared with 19% of controls (odds ratio [OR] 0.17; P 5 .009, Fisher’s exact test) with a similar trend after the second vaccination where 28% of patients were devoid of detectable specific T-cell immunity, compared with 6% of controls (OR 0.18; P 5 .02, Fisher’s exact test). Importantly, lack of T-cell reactivity to S1 peptides after vaccination heralded substandard levels (,100 BAU/mL) of anti–RBD-S1 IgG 5 to 6 months after the second vaccine dose (OR 8.2; P 5 .007, Fisher’s exact test). We conclude that although allo-HSCT recipients achieve serum anti–RBD-S1 IgG against SARS-CoV-2 after 2 vaccinations, a deficiency of SARS-CoV-2–specific T-cell immunity may subsequently translate into insufficient humoral responses.
Author
Sigrun Einarsdottir
University of Gothenburg
Anna Martner
University of Gothenburg
Jesper Waldenström
Sahlgrenska University Hospital
University of Gothenburg
Malin Nicklasson
University of Gothenburg
Johan Ringlander
University of Gothenburg
Sahlgrenska University Hospital
Mohammad Arabpour
University of Gothenburg
Sahlgrenska University Hospital
Andreas Törnell
University of Gothenburg
Hanna Grauers Wiktorin
University of Gothenburg
Staffan Nilsson
Chalmers, Mathematical Sciences, Applied Mathematics and Statistics
University of Gothenburg
Rudy Bittar
University of Gothenburg
Malin S. Nilsson
Sahlgrenska University Hospital
Mikael Lisak
University of Gothenburg
Malin Veje
University of Gothenburg
Vanda Friman
University of Gothenburg
Samer Al-Dury
Wallenberg Lab.
Tomas Bergström
Sahlgrenska University Hospital
University of Gothenburg
Per Ljungman
Karolinska University Hospital
Karolinska Institutet
Mats Brune
University of Gothenburg
Kristoffer Hellstrand
Sahlgrenska University Hospital
University of Gothenburg
Martin Lagging
Sahlgrenska University Hospital
University of Gothenburg
Blood Advances
24739529 (ISSN) 24739537 (eISSN)
Vol. 6 9 2723-2730Subject Categories (SSIF 2011)
Infectious Medicine
Immunology in the medical area
Gastroenterology and Hepatology
Hematology
DOI
10.1182/bloodadvances.2021006937
PubMed
35286374