A chimeric hemagglutinin-based universal influenza virus vaccine approach induces broad and long-lasting immunity in a randomized, placebo-controlled phase I trial
A chimeric hemagglutinin-based universal influenza virus vaccine approach induces broad and long-lasting immunity in a randomized, placebo-controlled phase I trial
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DOI：
10.1038/s41591-020-1118-7
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发表时间：
2020-12-07
期刊：
影响因子：
82.9
通讯作者：
Krammer, Florian
中科院分区：
文献类型：
--
作者：
Nachbagauer, Raffael;Feser, Jodi;Krammer, Florian
在人体中测试的新流感病毒疫苗可引发广泛的交叉反应抗体，这些抗体可结合病毒血凝素蛋白的茎，并可作为设计通用流感疫苗的模板。季节性流感病毒通过抗原漂移不断发生变化，大流行性流感病毒通过抗原漂移的出现是不可预测的。传统流感病毒疫苗诱导针对病毒血凝素蛋白的可变免疫显性球形头部结构域的株特异性中和抗体。这就需要经常重新配制疫苗，并妨碍大流行的防范工作。在这项完整的、观察者盲、随机、安慰剂对照的I期试验（NCT03300050）中，在18-39岁的健康美国成年人中测试了嵌合血凝素疫苗的安全性和免疫原性。该研究旨在测试疫苗引发针对血凝素柄结构域的广泛交叉反应抗体的安全性和能力。参与者被分为五组，分别接种减毒活疫苗和as03佐剂灭活疫苗（n = 20）、减毒活疫苗和灭活疫苗（n = 15）、两次as03佐剂灭活疫苗（n = 16）或安慰剂（n = 5，鼻内注射和肌肉注射；n = 10，两次肌肉注射），间隔3个月。研究发现，接种疫苗是安全的，并能诱导广泛、强烈、持久和功能性的免疫应答，靶向血凝素保守的免疫亚显性柄。这一结果表明，嵌合血凝素有潜力被开发成广泛预防流感病毒的通用疫苗。
New influenza virus vaccines tested in humans elicit broadly cross-reactive antibodies that bind the stalk of the viral hemagglutinin protein and may serve as templates to design a universal influenza vaccine.Seasonal influenza viruses constantly change through antigenic drift and the emergence of pandemic influenza viruses through antigenic shift is unpredictable. Conventional influenza virus vaccines induce strain-specific neutralizing antibodies against the variable immunodominant globular head domain of the viral hemagglutinin protein. This necessitates frequent re-formulation of vaccines and handicaps pandemic preparedness. In this completed, observer-blind, randomized, placebo-controlled phase I trial (NCT03300050), safety and immunogenicity of chimeric hemagglutinin-based vaccines were tested in healthy, 18-39-year-old US adults. The study aimed to test the safety and ability of the vaccines to elicit broadly cross-reactive antibodies against the hemagglutinin stalk domain. Participants were enrolled into five groups to receive vaccinations with live-attenuated followed by AS03-adjuvanted inactivated vaccine (n = 20), live-attenuated followed by inactivated vaccine (n = 15), twice AS03-adjuvanted inactivated vaccine (n = 16) or placebo (n = 5, intranasal followed by intramuscular; n = 10, twice intramuscular) 3 months apart. Vaccination was found to be safe and induced a broad, strong, durable and functional immune response targeting the conserved, immunosubdominant stalk of the hemagglutinin. The results suggest that chimeric hemagglutinins have the potential to be developed as universal vaccines that protect broadly against influenza viruses.