A Vaccine Displaying a Trimeric Influenza-A HA Stem Protein on Capsid-Like Particles Elicits Potent and Long-Lasting Protection in Mice

Due to constant antigenic drift and shift, current influenza-A vaccines need to be redesigned and administered annually. A universal flu vaccine (UFV) that provides long-lasting protection against both seasonal and emerging pandemic influenza strains is thus urgently needed. The hemagglutinin (HA) stem antigen is a promising target for such a vaccine as it contains neutralizing epitopes, known to induce cross-protective IgG responses against a wide variety of influenza subtypes. In this study, we describe the development of a UFV candidate consisting of a HA_stem trimer displayed on the surface of rigid capsid-like particles (CLP). Compared to soluble unconjugated HA_stem trimer, the CLP-HA_stem particles induced a more potent, long-lasting immune response and were able to protect mice against both homologous and heterologous H1N1 influenza challenge, even after a single dose.