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两种基于RNA的COVID-19候选疫苗的安全性和免疫原性
Safety and Immunogenicity of Two RNA-Based Covid-19 Vaccine Candidates


Edward E. Walsh ... 呼吸系统疾病 • 2020.12.17
相关阅读
• 保证SARS-CoV-2疫苗的安全性 • 我们为什么仍然需要对COVID-19疫苗开展安慰剂对照试验 • SARS-CoV-2疫苗接种——一分预防胜似十分治疗 • BNT162b2 COVID-19 mRNA疫苗的安全性和有效性 • 推进RNA疫苗研发工作 • 以疾病大流行的速度开发针对COVID-19的疫苗

摘要


背景

SARS-CoV-2感染及其所致疾病COVID-19已累及全球数百万人。多种候选疫苗正在开发中,但目前尚无疫苗上市。之前在德国和美国进行的试验已报告了在年轻成人接种候选疫苗BNT162b1后的期中安全性和免疫原性数据。

 

方法

在一项正在于美国进行的安慰剂对照、观察者设盲、剂量渐增、1期试验中,我们将18~55岁和65~85岁的健康成人随机分组,分别接种安慰剂或两种使用脂质纳米颗粒制成的核苷修饰RNA候选疫苗之一:BNT162b1(编码分泌的三聚体SARS-CoV-2受体结合域)和BNT162b2(编码以融合前构象保持稳定的膜锚定的SARS-CoV-2全长刺突蛋白)。主要结局是安全性(如局部和全身性反应及不良事件);免疫原性是次要结局。试验组根据候选疫苗、参与者年龄和疫苗剂量(10 μg、20 μg、30 μg和100 μg)进行定义。除一组之外,所有组参与者均间隔21日接种两剂疫苗;一组(100 μg BNT162b1)参与者接种一剂疫苗。

 

结果

共计195例参与者被随机分组。13组中每组有15例参与者,其中12例接种了疫苗,3例接种了安慰剂。BNT162b2的全身性反应发生率和严重程度均低于BNT162b1,特别是在老年人中。在年轻成人和老年人中,两种候选疫苗诱导产生了相似的剂量依赖性SARS-CoV-2中和几何平均滴度,均类似于或高于SARS-CoV-2感染者恢复期血清盘样本中的几何平均滴度。

 

结论

美国此项1期试验中年轻成人和老年人接种两种候选疫苗后的安全性和免疫原性数据,加上之前德国和美国试验中年轻成人接种BNT162b1后的期中安全性和免疫原性数据,支持选择BNT162b2开展旨在评估安全性和有效性的进一步关键2-3期研究(由BioNTech和辉瑞资助,在ClinicalTrials.gov注册号为NCT04368728)。





作者信息

Edward E. Walsh, M.D., Robert W. Frenck, Jr., M.D., Ann R. Falsey, M.D., Nicholas Kitchin, M.D., Judith Absalon, M.D., Alejandra Gurtman, M.D., Stephen Lockhart, D.M., Kathleen Neuzil, M.D., Mark J. Mulligan, M.D., Ruth Bailey, B.Sc., Kena A. Swanson, Ph.D., Ping Li, Ph.D., Kenneth Koury, Ph.D., Warren Kalina, Ph.D., David Cooper, Ph.D., Camila Fontes-Garfias, B.Sc., Pei-Yong Shi, Ph.D., Özlem Türeci, M.D., Kristin R. Tompkins, B.Sc., Kirsten E. Lyke, M.D., Vanessa Raabe, M.D., Philip R. Dormitzer, M.D., Kathrin U. Jansen, Ph.D., Uğur Şahin, M.D., and William C. Gruber, M.D.
From the University of Rochester and Rochester General Hospital, Rochester (E.E.W., A.R.F.), Vaccine Research and Development, Pfizer, Pearl River (J.A., A.G., K.A.S., K.K., W.K., D.C., K.R.T., P.R.D., K.U.J., W.C.G.), and New York University Langone Vaccine Center and Grossman School of Medicine, New York (M.J.M., V.R.) — all in New York; Cincinnati Children’s Hospital, Cincinnati (R.W.F.); Vaccine Research and Development, Pfizer, Hurley, United Kingdom (N.K., S.L., R.B.); the University of Maryland School of Medicine, Center for Vaccine Development and Global Health, Baltimore (K.N., K.E.L.); Vaccine Research and Development, Pfizer, Collegeville, PA (P.L.); the University of Texas Medical Branch, Galveston (C.F.-G., P.-Y.S.); and BioNTech, Mainz, Germany (ÖT., U.Ş.). Address reprint requests to Dr. Absalon at Pfizer, 401 N. Middletown Rd., Pearl River, NY 10965, or at judith.absalon@pfizer.com.

 

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