Evaluation of Pre-Pandemic Trivalent COBRA HA Vaccine in Mice Pre-Immune to Historical H1N1 and H3N2 Influenza Viruses

Initial exposure to influenza virus(es) during early childhood produces protective antibodies that may be recalled following future exposure to subsequent viral infections or vaccinations. Most influenza vaccine research studies use immunologically naïve animal models to assess vaccine effectiveness. However, most people have an extensive influenza immune history, with memory cells produced by viruses or vaccines representing multiple influenza viruses. In this study, we explored the effect influenza seasonal virus-induced immunity has on pre-pandemic influenza virus vaccination. The mice that were pre-immune to historical H1N1 and H3N2 seasonal influenza viruses were vaccinated with adjuvanted pre-pandemic (H2, H5, and H7) HA-based computationally optimized broadly reactive antigen (COBRA) vaccines, and were fully protected from lethal challenge, whereas the mock-vaccinated mice, with or without pre-immunity, were not protected from morbidity or mortality. Detectable antibody titers were present in the pre-immune mice vaccinated with a single dose of vaccine, but not in the immunologically naïve mice. The mice vaccinated twice with the trivalent COBRA HA vaccine had similar antibody titers regardless of their pre-immune status. Overall, seasonal pre-immunity did not interfere with the immune responses elicited by pre-pandemic COBRA HA vaccines or the protection against pre-pandemic viruses.