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).

中文翻译：

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同种异体造血干细胞移植受者对 BNT162b2 疫苗接种的中和抗体反应的预测因素


影响同种异体造血干细胞移植 (allo-HCT) 受者对 SARS-CoV-2 mRNA 疫苗反应的因素仍有待阐明。在第 0 天和第 21 天使用 BNT162b2 mRNA 疫苗进行免疫研究中纳入了 40 名异基因 HCT 接受者。在第 0 天、第 21 天、第 28 天和第 28 天评估了 SARS-CoV-2 受体结合域 (RBD) 的结合抗体 (Ab)。 49 在第 0 天和第 49 天评估了中和 SARS-CoV-2 野生型抗体 (NT50) 的情况。在异基因 HCT 患者中观察到的结果与在 40 名未感染 SARS-CoV-2 的健康成年人中获得的结果进行了比较。在疫苗接种前对外周血细胞进行流式细胞术分析，以确定抗体反应的潜在预测因子。三名患者在接种疫苗前已检测到抗 RBD 抗体。在 37 名 SARS-CoV-2 初治患者中，20 名 (54%) 和 32 名 (86%) 患者在疫苗接种后 21 天和 49 天检测到抗 RBD 抗体。比较 allo-HCT 接受者和健康成人的抗 RBD 抗体水平，我们观察到第 21、28 和 49 天时 allo-HCT 接受者的抗 RBD 抗体水平显着降低。此外，49% 的 allo-HCT 患者与 88% 的健康成年人在第 49 天时可检测到 NT50 Ab，而同种异体 HCT 接受者的 NT50 Ab 滴度显着低于健康成年人 (P = 0.0004)。在多变量分析中，持续中度/重度慢性 GVHD (P < 0.01) 以及接种前一年服用利妥昔单抗 (P < 0.05) 与首次接种疫苗后 49 天时的低抗 RBD 和 NT50 Ab 滴度相关。与健康成人相比，未接受慢性 GVHD 或利妥昔单抗治疗的异基因 HCT 患者在第 49 天时具有相当的抗 RBD 抗体水平和 NT50 抗体滴度。 疫苗接种前的流式细胞术分析表明，allo-HCT 患者的抗体反应与记忆 B 细胞和初始 CD4+ T 细胞的数量密切相关（r > 0.5，P < 0.01），与滤泡辅助 T 细胞的数量关系更弱。 （r = 0.4，P = 0.01）。同种异体 HCT 受者中的慢性 GVHD 和利妥昔单抗给药与 BNT162b2 疫苗接种的抗体反应降低有关。免疫标记物可以帮助识别异基因 HCT 患者，该患者面临对 mRNA 疫苗接种反应不佳的风险。该研究于 2021 年 3 月 11 日在 ClinicalTrialsregister.eu 注册（EudractCT # 2021-000673-83）。