Department of Hematology and Transplantology, Medical University of Gdansk, Gdansk, Poland.
Department of Endocrinology and Internal Diseases, Medical University of Gdansk, Gdansk, Poland.
Front Immunol. 2020 Nov 24;11:586523. doi: 10.3389/fimmu.2020.586523. eCollection 2020.
The immunization of allogeneic hematopoietic cell transplantation (HCT) recipients against vaccine-preventable diseases is a part of posttransplantation guidelines. We conducted a prospective study to assess clinical and immunological parameters that would determine the response and long-term maintenance of protective antibody titers upon the hepatitis B virus (HBV) vaccination after HCT. The investigated variables included: vaccination of the HCT recipients and their donors prior to HCT, chronic graft versus host disease (cGVHD) and the timing of post-HCT vaccination, and B- and T-cell subtype status. Forty-two patients were immunized with three or more doses of recombinant hepatitis B surface antigen (rHBsAg) administered according to the individualized schedule of 0-1-2-6-(12) months. After vaccination, seroconversion was achieved in the whole group. The vaccines were categorized according to the antibody (Ab) titers as weak (WRs; 28.7%), good (GRs; 38%) or very good responders (VGRs; 3.3%). In multivariate logistic regression, severe cGVHD (OR= 15.5), and preceding donor immunization (OR= 0.13) were independent predictors of a weak response to vaccination. A prior belonging to the WR group impaired the durability of protection (OR= 0.17) at a median follow-up of 11.5 years. Patients with severe cGVHD showed a trend toward lower median Ab titers, although they required a higher rate of booster vaccine doses. All VGRs had CD4+ cells > 0.2 x 10/L. There was a lower mean rate of CD4+IL2+ lymphocytes in WRs. Vaccination demonstrated the immunomodulatory effect on B-cell and T-cell subsets and a Th1/Th2 cytokine profile, while shifts depended on a history of severe cGVHD and the type of vaccine responder. To conclude, vaccination of HCT donors against HBV allows a better response to vaccination in the respective HCT recipients. Double doses of rHBsAg should be considered in patients with cGVHD and in those not immunized before HCT. A dedicated intensified vaccination schedule should be administered to WRs.
异基因造血细胞移植（HCT）受者接种疫苗以预防可通过疫苗预防的疾病是移植后指南的一部分。我们进行了一项前瞻性研究，以评估临床和免疫参数，这些参数将确定 HBV 疫苗接种后 HCT 后保护性抗体滴度的反应和长期维持。研究的变量包括：HCT 受者及其供者在 HCT 前的疫苗接种、慢性移植物抗宿主病（cGVHD）和 HCT 后疫苗接种的时间，以及 B 细胞和 T 细胞亚群状态。42 例患者接受了三剂或更多剂量的重组乙型肝炎表面抗原（rHBsAg）免疫接种，根据 0-1-2-6-（12）个月的个体化方案进行。接种疫苗后，整个组均实现了血清转换。根据抗体（Ab）滴度将疫苗分为弱反应者（WRs；28.7%）、良好反应者（GRs；38%）或非常好反应者（VGRs；3.3%）。在多变量逻辑回归中，严重的 cGVHD（OR=15.5）和供者免疫接种（OR=0.13）是疫苗接种弱反应的独立预测因子。先前属于 WR 组会损害保护的持久性（OR=0.17），中位随访时间为 11.5 年。患有严重 cGVHD 的患者表现出较低的 Ab 滴度中位数趋势，尽管他们需要更高的疫苗加强剂量。所有 VGR 均有 CD4+细胞>0.2x10/L。WRs 的平均 CD4+IL2+淋巴细胞率较低。疫苗接种对 B 细胞和 T 细胞亚群以及 Th1/Th2 细胞因子谱产生了免疫调节作用，而这种转变取决于严重 cGVHD 的病史和疫苗反应类型。总之，HCT 供者接种 HBV 疫苗可使相应的 HCT 受者对疫苗接种产生更好的反应。对于患有 cGVHD 的患者和 HCT 前未免疫的患者，应考虑使用 rHBsAg 的双剂量。应向 WR 提供专门的强化疫苗接种方案。
