Safety and Antibody Response After 1 and 2 Doses of BNT162b2 mRNA Vaccine in Recipients of Allogeneic Hematopoietic Stem Cell Transplant

Bourgeois, Amandine Le; Coste‐Burel, Marianne; Guillaume, Thierry; Péterlin, Pierre; Garnier, Alice; Béné, Marie C.; Chevallier, Patrice

doi:10.1001/jamanetworkopen.2021.26344

Cited by 61 publications

(94 citation statements)

References 8 publications

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“…However, due to the relatively small number of patients in our study group, this result should be interpreted with caution. We also found a stronger immunologic response in younger patients, which is an expected result in concordance with observations of COVID-19 mRNA vaccine immunity in the general population [ 20 , 21 ]. Interestingly, we also found an association between transplant conditioning intensity in alloHCT and seroconversion after vaccination.…”

Section: Discussionsupporting

confidence: 92%

Two Doses of BNT162b2 mRNA Vaccine in Patients after Hematopoietic Stem Cell Transplantation: Humoral Response and Serological Conversion Predictors

Majcherek

Matkowska-Kocjan

Szymczak

et al. 2022

Cancers

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Vaccination against SARS-CoV-2 is currently the best tool in the fight against the COVID-19 pandemic. However, there are limited data on its efficacy and safety after hematopoietic stem cell transplantation (HCT). We present the results of a prospective analysis of the humoral response to two doses of BNT162b2 mRNA vaccine in 93 adult patients, including 29 after autologous HCT (autoHCT) and 64 after allogeneic HCT (alloHCT). Positive anti-SARS-CoV-2 antibodies were detected before vaccination in 25% of patients despite a negative medical history of COVID-19. Seroconversion after vaccination was achieved in 89% of patients after alloHCT and in 96% after autoHCT, without grade 3/4 adverse events. Post-vaccination anti-SARS-CoV-2 antibody level correlated with the time from transplant and absolute B-cell count at the vaccination. In univariate analysis restricted to the alloHCT group, short time since transplantation, low B-cell count, low intensity conditioning, GvHD, and immunosuppressive treatment at the vaccination were associated with lack of seroconversion. In the multivariate model, the only negative predictor of seroconversion remained treatment with calcineurin inhibitor (CNI). In conclusion, the BNT162b2 mRNA vaccine is highly immunogenic in patients after HCT, but treatment with CNI at the time of vaccination has a strong negative impact on the humoral response

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Section: Discussionsupporting

confidence: 92%

Two Doses of BNT162b2 mRNA Vaccine in Patients after Hematopoietic Stem Cell Transplantation: Humoral Response and Serological Conversion Predictors

Majcherek

Matkowska-Kocjan

Szymczak

et al. 2022

Cancers

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“…Strong anti-S1 humoral immune responses are observed with current SARS-CoV-2 vaccines in the majority of alloSCT recipients off immunosuppression eliciting titres similar to those detected in healthy controls [3]. In contrast to other studies with smaller patient cohorts, our study comprised both mRNA-and vector-based vaccines [1,10]. It clearly shows that tandem mRNA-based vaccinations or combination strategies consisting of vector first followed by mRNA appear to elicit considerably higher titres than tandem vector vaccinations.…”

Section: Discussionmentioning

confidence: 94%

Humoral Responses and Chronic GVHD Exacerbation after COVID-19 Vaccination Post Allogeneic Stem Cell Transplantation

et al. 2022

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The COVID-19 pandemic threatens patients with a compromised immune and endothelial system, including patients who underwent allogeneic stem cell transplantation (alloSCT). Thus, there is an unmet need for optimizing vaccination management in this high-risk cohort. Here, we monitored antibodies against SARS-CoV-2 spike protein (anti-S1) in 167 vaccinated alloSCT patients. Humoral immune responses were detectable in 81% of patients after two vaccinations with either mRNA-, vector-based, or heterologous regimens. Age, B-cell counts, time interval from vaccination, and the type of vaccine determined antibody titres in patients without systemic immunosuppression (sIS). Similar to a healthy control cohort, mRNA vaccine-based regimens induced higher titres than vector-based vaccines. Patients on two or more immunosuppressants rarely developed immunity. In contrast, 62% and 45% of patients without or on only one immunosuppressant, respectively, showed a strong humoral vaccination response (titre > 100). Exacerbation of cGVHD upon vaccination was observed in 6% of all patients and in 22% of patients receiving immunosuppression for cGVHD. cGVHD exacerbation and low antibody titres were both associated with higher angiopoietin-2 (ANG2) serum levels. In conclusion, mRNA-based vaccines elicit strong humoral responses in alloSCT patients in the absence of double sIS. Biomarkers such as ANG2 might help with weighing cGVHD risk versus beneficial responses.

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“…48 BNT162b2 antibody studies show high antibody titers (same specific antibodies as above) postvaccination that wane by 2-6 months (more rapidly in immunosuppressed adults), and increase with boosting. [16][17][18][19][20][21][22][23][24] VE studies show high protection against infection with durability for 6 months (90-95%) earlier in the pandemic when Alpha and Beta variants predominated, but with waning to as low as 20% later when Beta and Delta variants predominated; VE against severe disease (hospitalization and death) remained high (>90%) throughout the pandemic. [29][30][31]34 VE against infection, severe infection, and mortality in Israel when Delta predominated was much higher with boosting.…”

Section: Discussionmentioning

confidence: 99%

Comparison of Antibody Response Durability of mRNA-1273, BNT162b2, and Ad26.COV2.S SARS-CoV-2 Vaccines in Healthcare Workers

Brunner

Freilich

Victory

et al. 2022

Preprint

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ImportanceThere is a dearth of comparative immunologic durability data after COVID-19 vaccinations.ObjectiveTo compare antibody responses and vaccine effectiveness 8.4 months post-primary COVID-19 vaccination.DesignSetting and Participants: In this cohort study of 903 healthcare workers who completed surveys about baseline characteristics and COVID-19 vaccine/infection history, 647 had antibody assays completed and were included herein.ExposureCOVID-19 vaccination with mRNA-1273 (n=387); BNT162b2 (n=212); or Ad26.COV2.S (n=10); unvaccinated (n=10); or boosted (n=28).Main Outcomes and MeasuresThe primary outcome was IgG anti-spike titer. Secondary/tertiary outcomes included IgG spike receptor-binding domain competitive antibody blocking ELISA pseudoneutralization against the USA-WA1/2020 strain, and vaccine effectiveness against COVID-19 infection. Antibody levels were compared using ANOVA and multiple linear regression.ResultsMean age was 49.7, 75.3% were female, and mean comorbidities/patient was 0.7. Baseline variables were balanced (p>.05) except for immunosuppression (higher in boosted, p=.047), prior COVID-19 infections (higher with Ad26.COV2.S and unvaccinated, p<.001), and time since primary vaccination (higher with mRNA-1273 and BNT162b2 than Ad26.COV2.S, p<.001).Unadjusted median (IQR) IgG anti-spike titers (AU/mL) were 1539.5 (876.7-2626.7) for mRNA-1273, 751.2 (422.0-1381.5) for BNT162b2, 451.6 (103.0-2396.7) for Ad26.COV2.S, 113.4 (3.7-194.0) for unvaccinated, and 31898.8 (21347.1-45820.1) for boosted (mRNA-1273 vs. BNT162b2, p<.001; mRNA-1273, BNT162b2, or boosted vs. unvaccinated, p<.006; mRNA-1273, BNT162b2, Ad26.COV2.S, or unvaccinated vs. boosted, p<.001; all other comparisons, p>.05). Unadjusted median (IQR) pseudoneutralization percentages were 90.9% (80.1-95.0) for mRNA-1273, 77.2% (59.1-89.9) for BNT162b2, 57.9% (36.6-95.8) for Ad26.COV2.S, 40.1% (21.7-60.6) for unvaccinated, and 96.4% (96.1-96.6) for boosted (mRNA-1273 vs. BNT162b2, p<.001; mRNA-1273, BNT162b2, or boosted vs. unvaccinated, p<.028; mRNA-1273, BNT162b2, Ad26.COV2.S, or unvaccinated vs. boosted, p<.001; all other comparisons, p>.05). Adjusted anti-spike and pseudoneutralization comparisons of mRNA-1273 and BNT162b2 showed similar patterns (p<.001). Vaccine effectiveness was 87-89% for mRNA-1273, BNT162b2, and boosted, and 33% for Ad26.COV2.S; no group differences were statistically significant.Conclusions and RelevanceDurability of antibody responses 8.4 months after COVID-19 primary vaccination was significantly higher with mRNA-1273 than with BNT162b2, however, vaccine effectiveness was equivalent. Antibody responses and vaccine effectiveness were lower but not significantly different for Ad26.COV2.S; given statistical uncertainty in the small Ad26.COV2.S group, clinically important effects cannot be excluded.

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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

Abstract: Open Access. This is an open access article distributed under the terms of the CC-BY License.

Cited by 61 publications

References 8 publications

Two Doses of BNT162b2 mRNA Vaccine in Patients after Hematopoietic Stem Cell Transplantation: Humoral Response and Serological Conversion Predictors

Two Doses of BNT162b2 mRNA Vaccine in Patients after Hematopoietic Stem Cell Transplantation: Humoral Response and Serological Conversion Predictors

Humoral Responses and Chronic GVHD Exacerbation after COVID-19 Vaccination Post Allogeneic Stem Cell Transplantation

Comparison of Antibody Response Durability of mRNA-1273, BNT162b2, and Ad26.COV2.S SARS-CoV-2 Vaccines in Healthcare Workers

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