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.

季节性流感病毒通过抗原漂移不断变化，而通过抗原漂移出现大流行性流感病毒是不可预测的。常规流感病毒疫苗诱导针对病毒血凝素蛋白的可变免疫显性球状头结构域的毒株特异性中和抗体。这需要频繁地重新配制疫苗并阻碍大流行的防范。在这项已完成的观察者盲法、随机、安慰剂对照 I 期试验 (NCT03300050) 中，在健康的 18-39 岁美国成年人中测试了基于嵌合血凝素的疫苗的安全性和免疫原性。该研究旨在测试疫苗的安全性和引发针对血凝素茎结构域的广泛交叉反应抗体的能力。参与者被分为五组，分别接种减毒活疫苗然后接种 AS03 佐剂灭活疫苗（ n = 20）、减毒活疫苗然后接种灭活疫苗（ n = 15）、两次 AS03 佐剂灭活疫苗（ n = 16）或安慰剂（ n = 5，鼻内随后肌肉注射； n = 10，两次肌肉注射），间隔 3 个月。研究发现，疫苗接种是安全的，并且可以针对血凝素的保守、免疫亚性茎部诱导广泛、强效、持久和功能性的免疫反应。结果表明，嵌合血凝素有潜力被开发为广泛预防流感病毒的通用疫苗。