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

• Published in: Journal of hematology and oncology Vol. 14; no. 1; p. 174
• Main Authors: Canti, Lorenzo, Humblet-Baron, Stéphanie, Desombere, Isabelle, Neumann, Julika, Pannus, Pieter, Heyndrickx, Leo, Henry, Aurélie, Servais, Sophie, Willems, Evelyne, Ehx, Grégory, Goriely, Stanislas, Seidel, Laurence, Michiels, Johan, Willems, Betty, Liston, Adrian, Ariën, Kevin K, Beguin, Yves, Goossens, Maria E, Marchant, Arnaud, Baron, Frédéric
• Format: Journal Article Web Resource
• Language: English
• Published: England BioMed Central Ltd 24.10.2021; BioMed Central; BMC
• Subjects: Adult; Aged; Allogeneic; Antibodies; Antibodies, Neutralizing - biosynthesis; Antibodies, Neutralizing - immunology; Antibody response; Antigens; Automation; B cells; Blood cells; BNT162 Vaccine; BNT162b2 mRNA vaccine; CD4 antigen; Comparative analysis; Coronaviruses; COVID-19; COVID-19 vaccines; COVID-19 Vaccines - immunology; COVID-19 Vaccines - therapeutic use; Dendritic cells; Flow cytometry; Graft versus host disease; Graft-versus-host reaction; Health aspects; Hematopoietic cell transplantation; Hematopoietic Stem Cell Transplantation - methods; Hematopoietic stem cells; Human health sciences; Humans; Immunological memory; Immunologie & maladie infectieuse; Immunology & infectious disease; Infection; Infections; Leukemia; Lymphocytes; Lymphocytes B; Lymphocytes T; Medical research; Medicine, Experimental; Memory cells; Middle Aged; mRNA; mRNA vaccines; Pain; Peripheral blood; Plasmacytoid dendritic cells; Rituximab; RNA; SARS-CoV-2; Sciences de la santé humaine; Severe acute respiratory syndrome coronavirus 2; Stem cell transplantation; Stem cells; Switched B cells; T cells; T-SNE; Transplantation; Transplantation Conditioning; Transplantation Immunology; Transplantation, Homologous; Transplants & implants; Vaccination; Vaccine; Beijing China; United States > US; China; Allogeneic; BNT162b2 mRNA vaccine; COVID-19; Hematopoietic cell transplantation; Plasmacytoid dendritic cells; SARS-CoV-2; T-SNE; Switched B cells; Vaccine
• ISSN: 1756-8722; 1756-8722
• DOI: 10.1186/s13045-021-01190-3

Factors affecting response to SARS-CoV-2 mRNA vaccine in allogeneic hematopoietic stem cell transplantation (allo-HCT) recipients remain to be elucidated. 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. 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). 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. The study was registered at clinicaltrialsregister.eu on 11 March 2021 (EudractCT # 2021-000673-83).