Predictors of neutralizing antibody response to BNT162b2 vaccination in allogeneic hematopoietic stem cell transplant recipients

Lorenzo Canti, Stephanie Humblet-Baron, Isabelle Desombere, Julika Neumann, Pieter Pannus, Leo Heyndrickx, Aurelie Henry, Sophie Servais, Evelyne Willems, Gregory Ehx, Stanislas Goriely, Laurence Seidel, Johan Michiels, Betty Willems, Adrian Liston, Kevin K. Ariën, Yves Beguin, Maria E. Goossens, Arnaud Marchant, Frederic Baron

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BACKGROUND: Factors affecting response to SARS-CoV-2 mRNA vaccine in allogeneic hematopoietic stem cell transplantation (allo-HCT) recipients remain to be elucidated.

METHODS: Forty allo-HCT recipients were included in a study of immunization with BNT162b2 mRNA vaccine at days 0 and 21. Binding antibodies (Ab) to SARS-CoV-2 receptor binding domain (RBD) were assessed at days 0, 21, 28, and 49 while neutralizing Ab against SARS-CoV-2 wild type (NT50) were assessed at days 0 and 49. Results observed in allo-HCT patients were compared to those obtained in 40 healthy adults naive of SARS-CoV-2 infection. Flow cytometry analysis of peripheral blood cells was performed before vaccination to identify potential predictors of Ab responses.

RESULTS: Three patients had detectable anti-RBD Ab before vaccination. Among the 37 SARS-CoV-2 naive patients, 20 (54%) and 32 (86%) patients had detectable anti-RBD Ab 21 days and 49 days postvaccination. Comparing anti-RBD Ab levels in allo-HCT recipients and healthy adults, we observed significantly lower anti-RBD Ab levels in allo-HCT recipients at days 21, 28 and 49. Further, 49% of allo-HCT patients versus 88% of healthy adults had detectable NT50 Ab at day 49 while allo-HCT recipients had significantly lower NT50 Ab titers than healthy adults (P = 0.0004). Ongoing moderate/severe chronic GVHD (P < 0.01) as well as rituximab administration in the year prior to vaccination (P < 0.05) correlated with low anti-RBD and NT50 Ab titers at 49 days after the first vaccination in multivariate analyses. Compared to healthy adults, allo-HCT patients without chronic GVHD or rituximab therapy had comparable anti-RBD Ab levels and NT50 Ab titers at day 49. Flow cytometry analyses before vaccination indicated that Ab responses in allo-HCT patients were strongly correlated with the number of memory B cells and of naive CD4 + T cells (r > 0.5, P < 0.01) and more weakly with the number of follicular helper T cells (r = 0.4, P = 0.01).

CONCLUSIONS: Chronic GVHD and rituximab administration in allo-HCT recipients are associated with reduced Ab responses to BNT162b2 vaccination. Immunological markers could help identify allo-HCT patients at risk of poor Ab response to mRNA vaccination.

TRIAL REGISTRATION: The study was registered at on 11 March 2021 (EudractCT # 2021-000673-83).

Original languageEnglish
Article number174
JournalJournal of Hematology & Oncology
Issue number1
Number of pages12
Publication statusPublished - 2021


  • Vaccine
  • BNT162b2 mRNA vaccine
  • SARS-CoV-2
  • COVID-19
  • Allogeneic
  • Hematopoietic cell transplantation
  • T-SNE
  • Switched B cells
  • Plasmacytoid dendritic cells


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