背景:镰状细胞病(SCD)患者发生侵袭性肺炎球菌疾病的风险很高。13价结合肺炎球菌疫苗(PCV13)和23价多糖疫苗(PPSV23)的免疫功效在患有SCD的成年人中鲜有记载。
方法:这是一项随机开放标记的2期研究,研究了PCV13在第(W)0周的免疫原性,然后在W4时使用PPSV23,而在W4时使用PPSV23。在W8评估应答者(血清型特异性IgG抗体增加4倍)与至少10个共有血清型的比例。次要终点是:i)几何平均滴度(GMT),ii)对0-1、2-5、6-9和10-12血清型的应答者,iii)肺炎球菌调理吞噬(OPA)活性,和iv)在W24和W96处的响应耐久性。
结果:总计,128例患者随机分为PCV13/PPSV23(n=63)或PPSV23单独组(n=65)。在W8时,PCV13/PPSV23和PPSV23组中分别有24.56%和8.20%的患者,分别,达到主要终点(p=0.016)。OPA应答者的这些数字分别为36.2%和8.7%(p=0.002)。PCV13/PPSV23组合策略提高了对0-1、2-5、6-9和10-12血清型的反应广度,占15.8%,35%,24.6%,24.6%对52.5%,31%,8%,PPSV23组为8%。在W96,对于五种血清型,PCV13/PPSV23的GMT显着高于单独的PPSV23组(4、14、19A,19F,23F).
结论:PCV13/PPSV23方案改善了成人SCD患者针对大量肺炎球菌血清型的抗体反应的广度和程度。免疫反应的可持续性需要召回策略。临床试验注册:NCT02274415。
Patients with sickle cell disease (SCD) are at high risk for invasive pneumococcal diseases. The immunological efficacy of 13-valent conjugate pneumococcal vaccine (PCV13) followed by a 23-valent polysaccharide vaccine (PPSV23) is poorly documented in adults with SCD.
This was a randomized open-labeled phase 2
study of the immunogenicity of PCV13 at week 0, followed by PPSV23 at week 4, compared with PPSV23 alone at week 4 in adult patients with SCD. The proportion of responders (4-fold increase in serotype-specific immunoglobulin [Ig] G antibodies) to ≥10 shared serotypes was assessed at week 8. Secondary end points were (1) geometric mean titers, (2) responders to 0-1, 2-5, 6-9, or 10-12 serotypes, (3) pneumococcal opsonophagocytic activity, and (4) response durability at weeks 24 and 96.
In total, 128 patients were randomized in the PCV13/PPSV23 (n = 63) or PPSV23-alone groups (n = 65). At week 8, 24.56% and 8.20% of patients from the PCV13/PPSV23 and PPSV23 groups, respectively, reached the primary end point (P = .02). These numbers were 36.2% and 8.7% for opsonophagocytic activity responders (P = .002). A combined PCV13/PPSV23 strategy improved the breadth of responses to 0-1, 2-5, 6-9, or 10-12 serotypes with 15.8%, 35%, 24.6%, and 24.6% versus 52.5%, 31%, 8%, and 8% in the PPSV23 group. At week 96, geometric mean titers were significantly higher in the PCV13/PPSV23 than in the PPSV23-alone group for 5 serotypes (4, 14, 19A, 19F, 23F).
A PCV13/PPSV23 regimen improved the breadth and magnitude of antibody responses against a large range of pneumococcal serotypes in adults with SCD. The sustainability of the immune response requires recall strategies.Clinical
Trial Registration: NCT02274415.