[en] 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).
Disciplines :
Immunology & infectious disease
Author, co-author :
Canti, Lorenzo ✱; Université de Liège - ULiège > GIGA I3 - Hematology
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Bibliography
Baron F, Efficace F, Cannella L, Willemze R, Vignetti M, Muus P, et al. Long-term follow-up of a trial comparing post-remission treatment with autologous or allogeneic bone marrow transplantation or intensive chemotherapy in younger acute myeloid leukemia patients. Haematologica. 2020;105:e13–6. DOI: 10.3324/haematol.2019.221333
Bosch M, Khan FM, Storek J. Immune reconstitution after hematopoietic cell transplantation. Curr Opin Hematol. 2012;19:324–35. DOI: 10.1097/MOH.0b013e328353bc7d
Hannon M, Beguin Y, Ehx G, Servais S, Seidel L, Graux C, et al. Immune recovery after allogeneic hematopoietic stem cell transplantation following Flu-TBI versus TLI-ATG conditioning. Clin Cancer Res Off J Am Assoc Cancer Res. 2015;21:3131–9. DOI: 10.1158/1078-0432.CCR-14-3374
Peric Z, Cahu X, Malard F, Brissot E, Chevallier P, Guillaume T, et al. Peripheral Blood plasmacytoid dendritic cells at day 100 can predict outcome after allogeneic stem cell transplantation. Biol Blood Marrow Transplant J Am Soc Blood Marrow Transplant. 2015;21:1431–6. DOI: 10.1016/j.bbmt.2015.04.003
Sharma A, Bhatt NS, St Martin A, Abid MB, Bloomquist J, Chemaly RF, et al. Clinical characteristics and outcomes of COVID-19 in haematopoietic stem-cell transplantation recipients: an observational cohort study. Lancet Haematol. 2021. 10.1016/S2352-3026(20)30429-4. DOI: 10.1016/S2352-3026(20)30429-4
Xhaard A, Xhaard C, D’Aveni M, Salvator H, Chabi M-L, Berceanu A, et al. Risk factors for a severe form of COVID-19 after allogeneic haematopoietic stem cell transplantation: a Société Francophone de Greffe de Moelle et de Thérapie cellulaire (SFGM-TC) multicentre cohort study. Br J Haematol. 2021. 10.1111/bjh.17260. DOI: 10.1111/bjh.17260
Roedl K, Heidenreich S, Pfefferle S, Jarczak D, Urbanowicz TT, Nörz D, et al. Viral dynamics of SARS-CoV-2 in critically ill allogeneic hematopoietic stem cell transplant recipients and immunocompetent patients with COVID-19. Am J Respir Crit Care Med. 2021;203:242–5. DOI: 10.1164/rccm.202009-3386LE
Pardi N, Hogan MJ, Naradikian MS, Parkhouse K, Cain DW, Jones L, et al. Nucleoside-modified mRNA vaccines induce potent T follicular helper and germinal center B cell responses. J Exp Med. 2018;215:1571–88. DOI: 10.1084/jem.20171450
Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, et al. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N Engl J Med. 2020. 10.1056/NEJMoa2034577. DOI: 10.1056/NEJMoa2034577
Walsh EE, Frenck RWJ, Falsey AR, Kitchin N, Absalon J, Gurtman A, et al. Safety and immunogenicity of two RNA-based Covid-19 vaccine candidates. N Engl J Med. 2020;383:2439–50. DOI: 10.1056/NEJMoa2027906
Sadarangani M, Marchant A, Kollmann TR. Immunological mechanisms of vaccine-induced protection against COVID-19 in humans. Nat Rev Immunol. 2021. 10.1038/s41577-021-00578-z. DOI: 10.1038/s41577-021-00578-z
Boyarsky BJ, Werbel WA, Avery RK, Tobian AAR, Massie AB, Segev DL, et al. Immunogenicity of a single dose of SARS-CoV-2 messenger RNA vaccine in solid organ transplant recipients. JAMA. 2021. 10.1001/jama.2021.4385. DOI: 10.1001/jama.2021.4385
Boyarsky BJ, Werbel WA, Avery RK, Tobian AAR, Massie AB, Segev DL, et al. Antibody response to 2-dose SARS-CoV-2 mRNA vaccine series in solid organ transplant recipients. JAMA. 2021;325:2204–6. DOI: 10.1001/jama.2021.7489
Herishanu Y, Avivi I, Aharon A, Shefer G, Levi S, Bronstein Y, et al. Efficacy of the BNT162b2 mRNA COVID-19 vaccine in patients with chronic lymphocytic leukemia. Blood. 2021. 10.1182/blood.2021011568. DOI: 10.1182/blood.2021011568
Goossens ME, Neven KY, Pannus P, Barbezange C, Thomas I, Van Gucht S, et al. Arch Public Health. 2021. 10.21203/rs.3.rs-310079/v1. DOI: 10.21203/rs.3.rs-310079/v1
Pannus P, Neven KY, De Craeye S, Heyndrickx L, Kerckhove SV, Georges D et al. Poor antibody response to BioNTech/Pfizer COVID-19 vaccination in SARS-CoV-2 naïve residents of nursing homes. medRxiv 2021; 2021.06.08.21258366.
Mariën J, Ceulemans A, Michiels J, Heyndrickx L, Kerkhof K, Foque N, et al. Evaluating SARS-CoV-2 spike and nucleocapsid proteins as targets for antibody detection in severe and mild COVID-19 cases using a Luminex bead-based assay. J Virol Methods. 2021;288:114025. DOI: 10.1016/j.jviromet.2020.114025
Van Gassen S, Callebaut B, Van Helden MJ, Lambrecht BN, Demeester P, Dhaene T, et al. FlowSOM: using self-organizing maps for visualization and interpretation of cytometry data. Cytom J Int Soc Anal Cytol. 2015;87:636–45. DOI: 10.1002/cyto.a.22625
Neumann J, Prezzemolo T, Vanderbeke L, Roca CP, Gerbaux M, Janssens S, et al. Increased IL-10-producing regulatory T cells are characteristic of severe cases of COVID-19. Clin Transl Immunol. 2020;9:e1204. DOI: 10.1002/cti2.1204
Pasciuto E, Burton OT, Roca CP, Lagou V, Rajan WD, Theys T, et al. Microglia require CD4 T cells to complete the fetal-to-adult transition. Cell. 2020;182:625-640.e24. DOI: 10.1016/j.cell.2020.06.026
Maneikis K, Šablauskas K, Ringelevičiūtė U, Vaitekėnaitė V, Čekauskienė R, Kryžauskaitė L, et al. Immunogenicity of the BNT162b2 COVID-19 mRNA vaccine and early clinical outcomes in patients with haematological malignancies in Lithuania: a national prospective cohort study. Lancet Haematol. 2021. 10.1016/S2352-3026(21)00169-1. DOI: 10.1016/S2352-3026(21)00169-1
Redjoul R, Le Bouter A, Beckerich F, Fourati S, Maury S. Antibody response after second BNT162b2 dose in allogeneic HSCT recipients. Lancet Lond Engl. 2021;398:298–9. DOI: 10.1016/S0140-6736(21)01594-4
Castermans E, Hannon M, Dutrieux J, Humblet-Baron S, Seidel L, Cheynier R, et al. Thymic recovery after allogeneic hematopoietic cell transplantation with non-myeloablative conditioning is limited to patients younger than 60 years of age. Haematologica. 2011;96:298–306. DOI: 10.3324/haematol.2010.029702
Forcade E, Kim HT, Cutler C, Wang K, Alho AC, Nikiforow S, et al. Circulating T follicular helper cells with increased function during chronic graft-versus-host disease. Blood. 2016;127:2489–97. DOI: 10.1182/blood-2015-12-688895
Cordonnier C, Labopin M, Chesnel V, Ribaud P, De La Camara R, Martino R, et al. Randomized study of early versus late immunization with pneumococcal conjugate vaccine after allogeneic stem cell transplantation. Clin Infect Dis Off Publ Infect Dis Soc Am. 2009;48:1392–401. DOI: 10.1086/598324
Jaffe D, Papadopoulos EB, Young JW, O’reilly RJ, Prockop S, Kernan NA, et al. Immunogenicity of recombinant hepatitis B vaccine (rHBV) in recipients of unrelated or related allogeneic hematopoietic cell (HC) transplants. Blood. 2006;108:2470–5. DOI: 10.1182/blood-2006-04-006981
Conrad A, Perry M, Langlois M-E, Labussière-Wallet H, Barraco F, Ducastelle-Leprêtre S, et al. Efficacy and safety of revaccination against tetanus, diphtheria, haemophilus influenzae type b and hepatitis B virus in a prospective cohort of adult recipients of allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant J Am Soc Blood Marrow Transplant. 2020;26:1729–37. DOI: 10.1016/j.bbmt.2020.05.006
Mohty B, Bel M, Vukicevic M, Nagy M, Levrat E, Meier S, et al. Graft-versus-host disease is the major determinant of humoral responses to the AS03-adjuvanted influenza A/09/H1N1 vaccine in allogeneic hematopoietic stem cell transplant recipients. Haematologica. 2011;96:896–904. DOI: 10.3324/haematol.2011.040386
Perry C, Luttwak E, Balaban R, Shefer G, Morales MM, Aharon A, et al. Efficacy of the BNT162b2 mRNA COVID-19 vaccine in patients with B-cell non-Hodgkin lymphoma. Blood Adv. 2021;5:3053–61. DOI: 10.1182/bloodadvances.2021005094
Apostolidis SA, Kakara M, Painter MM, Goel RR, Mathew D, Lenzi K et al. Altered cellular and humoral immune responses following SARS-CoV-2 mRNA vaccination in patients with multiple sclerosis on anti-CD20 therapy. medRxiv 2021; 2021.06.23.21259389.
Ram R, Hagin D, Kikozashvilli N, Freund T, Amit O, Bar-On Y, et al. Safety and immunogenicity of the BNT162b2 mRNA COVID-19 vaccine in patients after allogeneic HCT or CD19-based CART therapy-A single-center prospective cohort study. Transplant Cell Ther. 2021. 10.1016/j.jtct.2021.06.024. DOI: 10.1016/j.jtct.2021.06.024
Baron F, Storer B, Maris MB, Storek J, Piette F, Metcalf M, et al. Unrelated donor status and high donor age independently affect immunologic recovery after nonmyeloablative conditioning. Biol Blood Marrow Transplant J Am Soc Blood Marrow Transplant. 2006;12:1176–87. DOI: 10.1016/j.bbmt.2006.07.004
Silva-Cayetano A, Foster WS, Innocentin S, Belij-Rammerstorfer S, Spencer AJ, Burton OT, et al. A booster dose enhances immunogenicity of the COVID-19 vaccine candidate ChAdOx1 nCoV-19 in aged mice. Med N Y N. 2021;2:243-262.e8.
Redjoul R, Le Bouter A, Parinet V, Fourati S, Maury S. Antibody response after third BNT162b2 dose in recipients of allogeneic HSCT. Lancet Haematol. 2021. 10.1016/S2352-3026(21)00274-X. DOI: 10.1016/S2352-3026(21)00274-X
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