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B-cell aplasia is the most powerful predictive marker for poor humoral response after BNT162b2 mRNA SARS-CoV-2 vaccines in recipients of allogeneic hematopoietic stem cell transplantation
Jullien, M., Bourgeois, A. L., Coste-Burel, M., Peterlin, P., Garnier, A., Rimbert, M., Imbert, B. M., Gouill, S. L., Moreau, P., Mahe, B., et al
Transplantation and cellular therapy. 2022
Abstract
BACKGROUND Little is known on the immune response to SARS-CoV-2 vaccination in recipients of allogeneic hematopoietic stem cell transplantation (Allo-HSCT). However, a few studies have reported that adequate protection could be provided to this population. OBJECTIVE(S): The purpose of this study was to evaluate which factors can predict the efficacy of SARS-CoV-2 vaccination in these specifically immunosuppressed patients. STUDY DESIGN Specific anti Spike (S) antibody responses were assessed in a cohort of 117 Allo-HSCT recipients after two injections of BNT162b2 mRNA SARS-CoV-2 vaccine (V1 and V2). Factors considered liable to influence the antibody response and analyzed in this series were the interval between Allo-HSCT and V1, donor source, recipient and donor age, current immunosuppressive/chemotherapy (I/C) treatment and levels of CD4(+)and CD8(+) T-cells, B-cells and NK-cells at the time of V1. RESULTS Overall, the S-antibody response rate, evaluated at a median of 35 days after V2, was 82.9% for the entire cohort, with 71 patients (61%) reaching the highest titre. In univariate analysis, a lower pre-V1 median total lymphocyte count, lower CD4+ T-cell and B-cell counts as well as ongoing I/C treatment and a haploidentical donor were characteristic of non-humoral responders. However, multiparameter analysis showed that B-cell aplasia was the only factor predicting the absence of a specific immune response (Odd Ratio 0.01, 95%CI [0.00 - 0.10], p <10(-3)). Indeed, the rate of humoral response was 9.1% in patients with B-cell aplasia, vs 95.9% in patients with a B-cell count higher than 0 (p<10(-9)). CONCLUSION(S): These results advocate for the prescription of anti-SARS-CoV-2 vaccination in Allo-HSCT recipients as early as peripheral B-cell levels can be detected, suggesting also a need for a close monitoring of B-cell reconstitution after Allo-HSCT.
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SARS-CoV-2 T-Cell Responses in Allogeneic Hematopoietic Stem Cell Recipients following Two Doses of BNT162b2 mRNA Vaccine
Clémenceau, B., Guillaume, T., Coste-Burel, M., Peterlin, P., Garnier, A., Le Bourgeois, A., Jullien, M., Ollier, J., Grain, A., Béné, M. C., et al
Vaccines. 2022;10(3)
Abstract
BACKGROUND At variance to humoral responses, cellular immunity after anti-SARS-CoV-2 vaccines has been poorly explored in recipients of allogeneic hematopoietic stem-cell transplantation (Allo-HSCT), especially within the first post-transplant years where immunosuppression is more profound and harmful. METHODS SARS-CoV-2 Spike protein-specific T-cell responses were explored after two doses of BNT162b2 mRNA vaccine in 45 Allo-HSCT recipients with a median time from transplant of less than 2 years by using INF-γ ELISPOT assay and flow-cytometry enumeration of CD4(+) and CD8(+) T lymphocytes with intracellular cytokine production of IFN-γ and TNF-α. RESULTS A strong TNF-α(+) response from SARS-CoV-2-specific CD4(+) T-cells was detected in a majority of humoral responders (89%) as well as in a consistent population of non-humoral responders (40%). CONCLUSIONS T-cells are likely to participate in protection against COVID-19 viral infection, even in the absence of detectable antibody response, especially in the first years post-transplant in Allo-HSCT recipients.
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Strong SARS-CoV-2 T-Cell Responses after One or Two COVID-19 Vaccine Boosters in Allogeneic Hematopoietic Stem Cell Recipients
Clémenceau, B., Le Bourgeois, A., Guillaume, T., Coste-Burel, M., Peterlin, P., Garnier, A., Jullien, M., Ollier, J., Grain, A., Béné, M. C., et al
Cells. 2022;11(19)
Abstract
A full exploration of immune responses is deserved after anti-SARS-CoV-2 vaccination and boosters, especially in the context of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Although several reports indicate successful humoral responses in such patients, the literature is scarce on cellular specific immunity. Here, both B- (antibodies) and T-cell responses were explored after one (V3 n = 40) or two (V4 n = 12) BNT162b2 mRNA vaccine boosters in 52 allo-HSCT recipients at a median of 755 days post-transplant (<1 year n = 9). Results were compared with those of 12 controls who had received only one booster (BNT162b2 n = 6; mRNA-1273 n = 6). All controls developed protective antibody levels (>250 BAU/mL) and anti-spike T-cell responses. Similarly, 81% of the patients developed protective antibody levels, without difference between V3 and V4 (82.5% vs. 75%, p = 0.63), and 85% displayed T-cell responses. The median frequency of anti-spike T cells did not differ either between controls or the whole cohort of patients, although it was significantly lower for V3 (but not V4) patients. COVID-19 infections were solely observed in individuals having received only one booster. These results indicate that four vaccine injections help to achieve a satisfactory level of both humoral and cellular immune protection in allo-HSCT patients.
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Effectiveness of a third dose of BNT162b2 anti-SARS-CoV-2 mRNA vaccine over a 6-month follow-up period in allogenic hematopoietic stem cells recipients
Chevallier, P., Jullien, M., Peterlin, P., Garnier, A., Le Bourgeois, A., Coste-Burel, M., Béné, M. C., Guillaume, T.
Hematological oncology. 2022
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Abstract
This study reports the effectiveness of three injections of BNT162b2 anti-SARS-CoV-2 mRNA vaccine in 141 Allo-HSCT recipients with a median follow-up of 6 months post-third shot. We demonstrate a long-term high protection of Allo-HSCT recipients since only 2 infections and one death related to COVID-19 occurred.
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Assessment of COVID-19 Incidence and Severity Among Recipients of Allogenic Stem Cell Transplant After 1 or 2 mRNA Booster Doses During the Omicron Wave in France
Letailleur, V., Le Bourgeois, A., Guillaume, T., Jullien, M., Coste-Burel, M., Béné, M. C., Chevallier, P.
JAMA network open. 2022;5(12):e2247534
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Safety and immunogenicity of a first dose of SARS-CoV-2 mRNA vaccine in allogeneic hematopoietic stem-cells recipients
Chevallier, P., Coste-Burel, M., Le Bourgeois, A., Peterlin, P., Garnier, A., Béné, M. C., Imbert, B. M., Drumel, T., Le Gouill, S., Moreau, P., et al
EJHaem. 2021
Abstract
This was a monocentric prospective study testing the efficacy and safety of a first injection of BNT162b2 (Pfizer-BioNTech) in 112 Allo-HSCT patients. Antibody response to SARS-CoV-2 spike protein receptor-binding domain was tested at the time of the second injection (Roche Elecsys). The study also included a non-randomized control arm of 26 healthy controls. This study shows that a first dose of SARS-CoV-2 messenger RNA vaccine is safe and provides a 55% rate of seroconversion in allotransplanted patients compared to 100% for the controls (p < 0.001). Factors influencing the absence of response in patients were recent transplantation (<2 years), lymphopenia (<1 × 10(9)/L) and immunosuppressive treatment or chemotherapy at the time of vaccination.
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Safety and Antibody Response After 1 and 2 Doses of BNT162b2 mRNA Vaccine in Recipients of Allogeneic Hematopoietic Stem Cell Transplant
Le Bourgeois, A., Coste-Burel, M., Guillaume, T., Peterlin, P., Garnier, A., Béné, M. C., Chevallier, P.
JAMA network open. 2021;4(9):e2126344
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Antibody Response after 2 and 3 doses of SARS-CoV-2 mRNA Vaccine in Allogeneic Hematopoietic Cell Transplant Recipients
Maillard, A., Redjoul, R., Klemencie, M., Labussiere-Wallet, H., Le Bourgeois, A., D'Aveni, M., Huynh, A., Berceanu, A., Marchand, T., Chantepie, S. P., et al
Blood. 2021
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A randomised, placebo-controlled phase 3 study to evaluate the efficacy and safety of ASP0113, a DNA-based CMV vaccine, in seropositive allogeneic haematopoietic cell transplant recipients
Ljungman, P., Bermudez, A., Logan, A. C., Kharfan-Dabaja, M. A., Chevallier, P., Martino, R., Wulf, G., Selleslag, D., Kakihana, K., Langston, A., et al
EClinicalMedicine. 2021;33:100787
Abstract
BACKGROUND Cytomegalovirus (CMV) is a complication of allogeneic haematopoietic cell transplantation (allo-HCT). ASP0113, a DNA-based vaccine, contains two plasmids encoding human CMV glycoprotein B and phosphoprotein 65 (pp65). We assessed ASP0113 in CMV-seropositive allo-HCT recipients. METHODS In this phase 3, randomised, placebo-controlled study, CMV-seropositive allo-HCT recipients were randomly assigned (1:1) via interactive response technology to receive five injections of 1?mL of 5?mg/mL ASP0113 or placebo. The pharmacist and designated staff were unblinded. Masked syringes maintained the blind for patients and study personnel. Efficacy and safety analyses included patients who received =1 dose of ASP0113/placebo. The primary efficacy endpoint was the proportion of allo-HCT recipients with composite all-cause mortality and adjudicated CMV end-organ disease (EOD) by 1 year post-transplant. ClinicalTrials.gov: NCT01877655 (not recruiting). FINDINGS Patients were recruited between Sept 11, 2013 and Sept 21, 2016. Overall, 501 patients received =1 dose of ASP0113 (n?=?246) or placebo (n?=?255). The proportion of patients with composite all-cause mortality and adjudicated CMV EOD by 1 year post-transplant was 35.4% (n?=?87) with ASP0113 and 30•2% (n?=?77) with placebo (odds ratio 1.27; 95% confidence interval: 0.87 to 1.85; p?=?0.205). Incidence of injection site-related treatment-emergent adverse events (TEAEs) was higher with ASP0113 than placebo. Overall incidence and severity of other TEAEs was similar between groups. T-cell response to pp65 increased over time and was greater with placebo than ASP0113 (p?=?0.027). INTERPRETATION ASP0113 did not reduce overall mortality or CMV EOD by 1 year post-transplant. Safety findings were similar between groups. FUNDING Astellas Pharma Global Development, Inc .