Vaccine Research and Development, Pfizer, Inc., Pearl River, NY, United States.
Vaccine Research and Development, Pfizer, Inc., Collegeville, PA, United States.
Vaccine. 2019 Sep 30;37(42):6201-6207. doi: 10.1016/j.vaccine.2019.08.048. Epub 2019 Sep 5.
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.
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.
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.
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.
肺炎链球菌是菌血症、细菌性肺炎和脑膜炎的主要病因，与大量发病率和死亡率有关，尤其是在 2 岁以下和 65 岁以上的人群中。虽然由于使用了肺炎球菌结合疫苗（PCV7、PCV10 和 PCV13），在防治肺炎球菌相关疾病方面取得了重大进展，但进一步扩大肺炎球菌疫苗血清型覆盖范围仍然具有重要意义。在这里，我们报告了一种 20 价肺炎球菌结合疫苗（PCV20）的首次应用，该疫苗包含 PCV13 中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。
这是一项 I 期首次人体研究，采用随机、对照、观察者盲法设计，评估 20 价肺炎球菌结合疫苗（PCV20）在成年人中的安全性、耐受性和免疫原性。共有 66 名无肺炎球菌疫苗接种史的 18-49 岁健康成年人入组，并随机接受一剂 PCV20 或一种已上市的破伤风、白喉、无细胞百日咳联合疫苗（Tdap）对照。评估局部注射部位反应、选择性全身症状、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）采集血清，检测血清中的调理吞噬活性（OPA）滴度和 IgG 浓度。
接种 PCV20 可引起 IgG 和功能杀菌免疫应答，表现为 IgG 几何平均浓度（GMC）和对 20 种疫苗血清型的调理吞噬活性几何平均滴度（GMT）增加。PCV20 的总体安全性与 Tdap 相似，与 PCV13 给药后的观察结果基本一致。
接种 PCV20 耐受性良好，可诱导对所有疫苗血清型的功能性（OPA）和 IgG 应答。在这项 I 期研究中未发现安全性问题，数据支持进一步评估 PCV20。
