Musocal vaccine for universal influenza A protection

Abstract The rapid mutation rate of the influenza virus requires that the yearly flu vaccine development cycle start months in advance of the flu season. The search for a single vaccine able to protect against multiple strains of influenza has thus long been the Holy Grail of flu vaccine research. Such a vaccine would require an antigenic target that is highly or completely homologous among all influenza subtypes. There is one such conserved region present on the otherwise highly variable influenza A hemagglutinin protein. This short, linear peptide sequence known as the fusion peptide is highly conserved among influenza A viral subtypes. Up until now, the difficulty generating strong immune responses against short peptide epitopes has prevented exploitation of this conserved region as a vaccine target. We previously developed a novel peptide adjuvant termed EP67 that induces mucosal and systemic adaptive immune responses to conjoined peptide sequences. In this study, we conjugated EP67 to the conserved influenza A fusion peptide sequence. The resulting peptide conjugate was then encapsulated in biodegradable PLGA 50:50 nanoparticles, and the nanoparticle vaccines were delivered to either the lungs or the nasal mucosal tissue. Preliminary testing shows that intranasal administration of our encapsulated peptide vaccine protects young mice from lethal infection with either H1N1 or H3N2 strains of influenza. Aged animals are also protected from lethal infection using this nanoparticle vaccine. These studies support the continued exploration mucosal nanoparticle vaccines containing conserved influenza sequences as a promising strategy for universal influenza protection.