(549a) Adjuvant Characterization for Virus-Like Particle-Based Influenza Vaccines

Influenza virus continues to pose serious pandemic risk largely due to antigenic drift. Current influenza vaccines predominantly provide strain specific protection. Our laboratory has engineered and fabricated novel virus-like particles that mimic native influenza viruses. Although we have demonstrated that multiple doses of influenza VLPs show protective immune response in mice, limited knowledge is available on the ability to enhance immune response using adjuvants through the intramuscular route to induce protection against a broader spectrum of influenza virus strains. It is also of interest to enable a single dose vaccination regimen as opposed to the current two dose influenza vaccination schedule.

In this study we investigated the effect of different water soluble adjuvants such as muramyl dipeptide, granulocyte macrophage colony-stimulating factor (GMCSF), CpG, poly (I:C) and gardiquimod on the immune response in mice. Adjuvants at a 1 µg dose were administered with influenza VLPs intramuscularly. Mouse serum antibodies were analyzed at weeks 2 and 4 post immunization with a booster dose to determine the effect of adjuvants. VLPs alone at a dose of 1 µg per mouse induced protection from lethal virus challenge. While all the different adjuvants tested showed increase in antibody levels, gardiquimod and CpG showed the highest increase.

In conclusion, we have fabricated virus-like particles that mimic native influenza viruses and produce protective immune response in mice. Gardiquimod and CpG were found to be potential adjuvants for VLPs. Effects of different doses of adjuvants on the immune response and on single dose-induced protective immunity by virus-like particle vaccine will also be discussed.