Phase 1 trial of a 20-valent pneumococcal conjugate vaccine in healthy adults
Phase 1 trial of a 20-valent pneumococcal conjugate vaccine in healthy adults
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DOI：
10.1016/j.vaccine.2019.08.048
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发表时间：
2019-09-30
期刊：
影响因子：
5.5
通讯作者：
Watson, Wendy
中科院分区：
文献类型：
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作者：
Thompson, Allison;Lamberth, Erik;Watson, Wendy
简介：肺炎链球菌是菌血症、细菌性肺炎和脑膜炎的主要原因，并与大量发病率和死亡率相关，特别是在 2 岁以下和 65 岁以上的人群中。虽然由于引入肺炎球菌结合疫苗（PCV7、PCV10 和 PCV13），针对肺炎链球菌相关疾病取得了重大进展，但进一步扩大肺炎球菌疫苗血清型覆盖范围仍然具有价值。在此，我们首次报告了 20 价肺炎球菌结合疫苗 (PCV20)，其中含有 PCV13 中存在的荚膜多糖结合物以及 7 种新血清型（8、10A、11A、12F、15B、22F 和 33F），这些血清型是肺炎球菌疾病的重要贡献者。方法：这项 I 期首次人体研究是一项随机、一项采用双臂平行设计的对照、观察者盲法研究，旨在评估 PCV20 在成人中的安全性、耐受性和免疫原性。共有 66 名 18-49 岁、无肺炎球菌疫苗接种史的健康成年人入组，并随机接受单剂 PCV20 或许可的破伤风、白喉、无细胞百日咳联合疫苗 (Tdap) 对照。评估了局部注射部位反应、选择的全身症状、实验室研究和不良事件。在接种前和接种后约 1 个月（28-35 天）收集的血清中测量调理吞噬活性 (OPA) 滴度和 IgG 浓度。结果：PCV20 疫苗接种可引发大量 IgG 和功能性杀菌免疫反应，20 种疫苗血清型的 IgG 几何平均浓度 (GMC) 和 OPA 几何平均滴度 (GMT) 增加证明了这一点。 PCV20 的总体安全性与 Tdap 相似，并且与 PCV13 给药后观察到的结果基本一致。结论：PCV20 疫苗接种耐受性良好，并诱导对所有疫苗血清型的实质性功能性 (OPA) 和 IgG 反应。本一期研究未发现任何安全问题，数据支持对 PCV20 的进一步评估。 (C) 2019 年由爱思唯尔有限公司出版。
Introduction: Streptococcus pneumoniae is a leading cause of bacteremia, bacterial pneumonia, and meningitis, and is associated with substantial morbidity and mortality, particularly in those under 2 years of age and those over 65 years of age. While significant progress against S. pneumoniae-related disease has been made as a result of the introduction of pneumococcal conjugate vaccines (PCV7, PCV10 and PCV13), there remains value in further expanding pneumococcal vaccine serotype coverage. Here we present the first report of a 20-valent pneumococcal conjugate vaccine (PCV20) containing capsular polysaccharide conjugates present in PCV13 as well as 7 new serotypes (8, 10A, 11A, 12F, 15B, 22F, and 33F) which are important contributors to pneumococcal disease.Methods: This Phase I first-in-human study was a randomized, controlled, observer-blinded study with a two-arm parallel design to assess the safety, tolerability, and immunogenicity of PCV20 in adults. A total of 66 healthy adults 18-49 years of age with no history of pneumococcal vaccination were enrolled and randomized to receive a single dose of PCV20 or a licensed tetanus, diphtheria, acellular pertussis combination vaccine (Tdap) control. Local injection site reactions, select systemic symptoms, laboratory studies, and adverse events were assessed. Opsonophagocytic activity (OPA) titers and IgG concentrations were measured in sera collected prior to, and approximately one month (28-35 days) after vaccination.Results: Vaccination with PCV20 elicited substantial IgG and functional bactericidal immune responses as demonstrated by increases in IgG geometric mean concentrations (GMCs) and OPA geometric mean titers (GMTs) to the 20 vaccine serotypes. The overall safety profile of PCV20 was similar to Tdap, and generally consistent with that observed after PCV13 administration.Conclusions: Vaccination with PCV20 was well tolerated and induced substantial functional (OPA) and IgG responses to all vaccine serotypes. There were no safety issues identified in this Phase 1 study, and the data supported further evaluation of PCV20. (C) 2019 Published by Elsevier Ltd.