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.

季节性流感病毒会通过抗原漂移不断变化，而大流行性流感病毒通过抗原漂移的出现是无法预测的。常规流感病毒疫苗诱导针对病毒血凝素蛋白的可变免疫优势球状头部结构域的菌株特异性中和抗体。这就需要频繁地重新配制疫苗，并阻碍大流行的防范。在这项完成的，观察者盲目的，随机，安慰剂对照的I期试验（NCT03300050）中，对健康的18至39岁美国成年人进行了嵌合血凝素疫苗的安全性和免疫原性测试。该研究旨在测试疫苗引发针对血凝素茎结构域的广泛交叉反应抗体的安全性和能力。n  = 20），减毒活疫苗，灭活疫苗（n  = 15），两次AS03辅助灭活疫苗（n  = 16）或安慰剂（n  = 5，鼻内接着是肌内；n  = 10，两次肌肉内）3个月分开。发现疫苗接种是安全的，并且针对血凝素的保守的，免疫优势的茎诱导了广泛，强，持久和功能性的免疫应答。结果表明，嵌合血凝素有可能被开发为广泛保护流感病毒的通用疫苗。