Immunogenicity, Safety, and Tolerability of 13-Valent Pneumococcal Conjugate Vaccine Followed by 23-Valent Pneumococcal Polysaccharide Vaccine in Recipients of Allogeneic Hematopoietic Stem Cell Transplant Aged ≥2 Years: An Open-Label Study
Immunogenicity, Safety, and Tolerability of 13-Valent Pneumococcal Conjugate Vaccine Followed by 23-Valent Pneumococcal Polysaccharide Vaccine in Recipients of Allogeneic Hematopoietic Stem Cell Transplant Aged ≥2 Years: An Open-Label Study
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DOI：
10.1093/cid/civ287
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发表时间：
2015-08-01
影响因子：
11.8
通讯作者：
Schmoele-Thoma, Beate
中科院分区：
文献类型：
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作者：
Cordonnier, Catherine;Ljungman, Per;Schmoele-Thoma, Beate
背景。造血干细胞移植（HSCT）后经常发生危及生命的肺炎链球菌感染；接种疫苗对预防很重要。在一项开放标签研究中，异体造血干细胞移植后3-6个月的患者（n = 251）每隔1个月接种3剂13价肺炎球菌结合疫苗（PCV13）， 6个月后接种第四剂，1个月后接种1剂23价肺炎球菌多糖疫苗（PPSV23）。在预先设定的时间点评估免疫原性和疫苗安全性。在可评估的免疫原性人群中（N = 216，平均年龄37.8岁），免疫球蛋白G几何平均浓度从基线到剂量3后的几何平均浓度显示，所有PCV13血清型的抗体水平显著增加（GMFR范围，2.99-23.85；95%置信区间下限，>.1）；在接下来的6个月内显著下降，从剂量4前到剂量4后显著增加（GMFR范围，3.00-6.97），PPSV23后变化不大（GMFR范围，0.86-1.12）。第4剂量后，局部和全身反应更为频繁。6例患者出现了可能与PCV13相关的严重不良事件（面部双瘫、注射部位红斑和发热、自身免疫性溶血性贫血、3剂后疑似缺乏疫苗效力导致肺炎球菌感染）、PCV13和PPSV23（格林-巴利综合征）或PPSV23（蜂窝组织炎）。有14例死亡，没有一例与研究疫苗有关。可能需要3剂PCV13方案，然后再加一剂加强剂，以保护HSCT受者免受肺炎球菌疾病的侵害。剂量4与局部和全身反应增加有关，但4剂量方案的总体安全性被认为是可以接受的。
Background. Life-threatening Streptococcus pneumoniae infections often occur after hematopoietic stem cell transplant (HSCT); vaccination is important for prevention.Methods. In an open-label study, patients (n = 251) 3-6 months after allogeneic HSCT received 3 doses of 13-valent pneumococcal conjugate vaccine (PCV13) at 1-month intervals, a fourth dose 6 months later, and 1 dose of 23-valent pneumococcal polysaccharide vaccine (PPSV23) 1 month later. Immunogenicity at prespecified time points and vaccine safety were assessed.Results. In the evaluable immunogenicity population (N = 216; mean age, 37.8 years), geometric mean fold rises (GMFRs) of immunoglobulin G geometric mean concentrations from baseline to postdose 3 showed significant increases in antibody levels across all PCV13 serotypes (GMFR range, 2.99-23.85; 95% confidence interval lower limit, >1); there were significant declines over the next 6 months, significant increases from predose 4 to postdose 4 (GMFR range, 3.00-6.97), and little change after PPSV23 (GMFR range, 0.86-1.12). Local and systemic reactions were more frequent after dose 4. Six patients experienced serious adverse events possibly related to PCV13 (facial diplegia, injection-site erythema and pyrexia, autoimmune hemolytic anemia, and suspected lack of vaccine efficacy after dose 3 leading to pneumococcal infection), PCV13 and PPSV23 (Guillain-Barre syndrome), or PPSV23 (cellulitis). There were 14 deaths, none related to study vaccines.Conclusions. A 3-dose PCV13 regimen followed by a booster dose may be required to protect against pneumococcal disease in HSCT recipients. Dose 4 was associated with increased local and systemic reactions, but the overall safety profile of a 4-dose regimen was considered acceptable.