METHODS FOR GENERATING BROADLY REACTIVE, PAN-EPITOPIC IMMUNOGENS, COMPOSITIONS AND METHODS OF USE THEREOF

Provided herein are methods for generating a non-naturally occurring, broadly reactive, pan-epitopic antigen derived from a pathogen, such as a virus, bacterium, and the like, that is immunogenic and is capable of eliciting a broadly reactive immune response, such as a broadly reactive neutralizing antibody response, against the pathogen following introduction into a subject. Also provided is a non-naturally occurring immunogen generated using the methods, and vaccines and compositions comprising the immunogen. Methods of generating an immune response in a subject by administering the immunogen, vaccine, or composition are provided. In particular, the immunogen comprises the hemagglutinin (HA) or neuraminidase (NA) protein of influenza virus strains. 本文提供产生源自蛋白(例如病毒、细菌等)的非自然发生、广泛反应、泛表位抗原的方法，其具有免疫原性并且能够在引入受试者后引发针对所述蛋白的广泛反应免疫反应，例如广泛反应中和抗体反应。亦提供使用所述方法产生的非自然发生的免疫原及疫苗及包含免疫原的组合物。提供了通过施用免疫原、疫苗或组合物在受试者中以产生免疫反应的方法。特别地，免疫原包含流感病毒株的血凝素(HA)蛋白或神经氨酸酶(NA)。