Pseudovirus nanoparticles targeting the receptor binding HA1 domains of influenza viruses elicited high HA1-specific antibody responses and protected mice against mortality caused by influenza virus challenges.

The continually high disease burden of influenza and the relatively low effectiveness of current influenza vaccines call for enhanced vaccine strategies. We previously generated unique S-HA1 pseudovirus nanoparticles (PVNPs) displaying the receptor binding HA1 antigens of the H7N9 subtype as an influenza vaccine candidate and characterized their features in biochemistry, biophysics, structure, and immune response. In this follow up study, we created new S-HA1 PVNPs displaying the HA1 antigens of other common influenza viruses, including two H1N1 strains, one H3N2 strain, and an influenza B virus, respectively. The recombinant PVNPs react well with antibodies against hemagglutinins (HAs) or mouse sera obtained after influenza virus challenge. 3D structural models were constructed to comprehend the structural features and size variations of the S-HA1 PVNPs. The PVNPs are immunogenic, eliciting high titers of HA1-specific serum antibodies that recognized commercial HA1 proteins. Importantly, the S-HA1 PVNP representing the H1N1 PR8 strain provided mice with 100 % protection against mortality caused by challenge with the mouse-adapted influenza virus of the same PR8 strain. The S-HA1 PVNP representing the H1N1 2009 pandemic strain conferred mice with 50 % protection against mortality caused by challenge with the 1934 PR8 strain, despite the two strains circulating 75 years apart. Our data demonstrated the feasibility of generating S-HA1 PVNPs to display HA1 antigens of diverse influenza A and B viruses. The readily available S-HA1 PVNPs hold promise as influenza vaccines, presenting a novel approach to combat the deadly influenza disease.