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

Thrane, Susan; Aves, Kara-Lee; Uddbäck, Ida E. M; Janitzek, Christoph M.; Han, Julianna; Yang, Yuhe R.; Ward, Andrew B.; Theander, Thor G.; Nielsen, Morten A.; Salanti, Ali; Thomsen, Allan R.; Christensen, Jan P.; Sander, Adam F.

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.