Section of Hematology, Department of Medicine, Faculty of Medicine and Health, Örebro University, SE 70185 Örebro, Sweden.
Section of Hematology, Department of Medicine, Faculty of Medicine and Health, Örebro University, SE 70185 Örebro, Sweden.
Vaccine. 2023 May 5;41(19):3128-3136. doi: 10.1016/j.vaccine.2023.04.016. Epub 2023 Apr 13.
Patients with chronic lymphocytic leukemia (CLL) show an immune dysfunction with increased risk of infections and poor response to vaccination. Streptococcus pneumoniae is a common cause of morbidity and mortality in CLL patients. In a previous randomized clinical trial, we found a superior immune response in CLL patients receiving conjugated pneumococcal vaccine compared to non-conjugated vaccine. The response to revaccination in CLL patients is scarcely studied. In this study, early humoral response to repeated revaccinations with pneumococcal vaccines was evaluated, by determination of B cell subsets and plasmablast dynamics in peripheral blood.
CLL patients (n = 14) and immunocompetent controls (n = 31) were revaccinated with a 13-valent pneumococcal conjugate vaccine (PCV13) after previous primary immunization (3-6 years ago) with PCV13 or a 23-valent pneumococcal polysaccharide vaccine (PPSV23). Eight weeks after the first revaccination, all CLL patients received a second revaccination with PCV13 or PPSV23. B cell subsets including plasmablasts were analyzed in peripheral blood by flow cytometry, before and after the first and the second revaccination.
None of the CLL patients, but all controls, had detectable plasmablasts at baseline (p < 0.001). After the first revaccination with PCV13, the plasmablast proportions did not increase in CLL patients (p = 0.13), while increases were seen in controls (p < 0.001). However, after a second revaccination with PCV13 or PPSV23, plasmablasts increased compared to baseline also in CLL patients (p < 0.01). If no response was evident after first revaccination, only a second revaccination with PCV13 increased plasmablasts in contrast to PPSV23 revaccination. Patients with hypogammaglobulinemia and ongoing/previous CLL specific treatment responded poorly, also to a second revaccination.
In CLL patients, pneumococcal revaccination induced minor early plasmablast response compared to controls, but the response improved using a strategy of repeated doses with of conjugated T cell dependent pneumococcal vaccine.
慢性淋巴细胞白血病（CLL）患者表现出免疫功能障碍，感染风险增加，对疫苗的反应不佳。肺炎链球菌是 CLL 患者发病和死亡的常见原因。在之前的一项随机临床试验中，我们发现接受结合型肺炎球菌疫苗接种的 CLL 患者的免疫反应优于非结合型疫苗。CLL 患者再次接种疫苗的反应鲜少被研究。在这项研究中，我们通过检测外周血中的 B 细胞亚群和浆母细胞动力学，评估了 CLL 患者多次重复接种肺炎球菌疫苗后的早期体液反应。
14 例 CLL 患者（n=14）和 31 例免疫功能正常的对照者（n=31）在之前接受过 13 价肺炎球菌结合疫苗（PCV13）或 23 价肺炎球菌多糖疫苗（PPSV23）初次免疫（3-6 年前）后，再次接种 13 价肺炎球菌结合疫苗（PCV13）。第一次接种后 8 周，所有 CLL 患者均再次接种 PCV13 或 PPSV23。通过流式细胞术在第一次和第二次接种前后分析外周血中的 B 细胞亚群，包括浆母细胞。
无一例 CLL 患者在基线时可检测到浆母细胞（p<0.001），而所有对照者均有浆母细胞。在第一次接种 PCV13 后，CLL 患者的浆母细胞比例没有增加（p=0.13），而对照者的浆母细胞比例则增加（p<0.001）。然而，在第二次接种 PCV13 或 PPSV23 后，与基线相比，CLL 患者的浆母细胞也增加（p<0.01）。如果第一次接种后没有明显的反应，只有第二次接种 PCV13 会增加浆母细胞，而第二次接种 PPSV23 则不会。低丙种球蛋白血症和正在进行/先前的 CLL 特异性治疗的患者反应不佳，即使进行第二次接种也如此。
与对照者相比，CLL 患者再次接种肺炎球菌疫苗可引起轻微的早期浆母细胞反应，但通过重复给予结合型 T 细胞依赖性肺炎球菌疫苗的策略，可改善反应。
