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

• DOI: 10.1186/s13045-021-01190-3
• Publication Date: 2021-10-24T16:02:40Z
• Authors: Lorenzo Canti; Stéphanie Humblet...; Isabelle Desombere; Julika Neumann; Pieter Pannus; Leo Heyndrickx; Aurélie Henry; Sophie Servais; Evelyne Willems; Grégory Ehx; Stanislas Goriely; Laurence Seidel; Johan Michiels; Betty Willems; Adrian Liston; Kevin K. Ariën; Yves Beguin; Maria E. Goossens; Arnaud Marchant; Frédéric Baron
• Keywords: Adult; 0301 basic medicine; COVID-19 Vaccines; Transplantation Conditioning; Switched B cells; T-SNE; IMMUNOGENICITY; COVID-19 VACCINE; 03 medical and health sciences; Transplantation Immunology; Immunologie; Humans; Transplantation, Homologous; Diseases of the blood and blood-forming organs; Allogeneic; RC254-282; BNT162 Vaccine; Aged; Science & Technology; BNT162b2 mRNA vaccine; Hematopoietic cell transplantation; SARS-CoV-2; Research; Hematopoietic Stem Cell Transplantation; COVID-19; Neoplasms. Tumors. Oncology. Including cancer and carcinogens; Hematology; RECOVERY; Middle Aged; EFFICACY; Antibodies, Neutralizing; 3. Good health; Oncology; Plasmacytoid dendritic cells; RC633-647.5; Life Sciences & Biomedicine; Vaccine; Hématologie

Abstract 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 clinicaltrialsregister.eu on 11 March 2021 (EudractCT # 2021-000673-83).