Intranasal influenza vaccination using an outer membrane vesicle platform

Influenza A vaccines have been used successfully for a long time to prevent disease, but most vaccines are produced using egg-based technologies that cause long production lead times and challenges to match circulating influenza strains. Furthermore, these vaccines are often given as intramuscular injections, which induce systemic immune responses but limited mucosal immunity. Mucosal vaccination strategies have been developed to prevent various air-borne respiratory infections, including influenza. An influenza A vaccine candidate was developed based on Outer Membrane Vesicles (OMVs) derived from genetically engineered bacteria. A plug-and-play-like technology allows for high-density covalent decoration of these OMVs with recombinant antigens to generate highly immunogenic mucosal vaccines. In the present study, the OMV-platform was used for the development of an intranasal influenza A vaccine candidate. Influenza A/Puerto Rico/8/1934 (H1N1) (PR8) hemagglutinin (HA) was produced in HEK-293-F suspension cells and coupled to OMVs. The vaccine substance was purified and formulated in a buffer suitable for mucosal administration, PBS + 15% glycerol. Mice were vaccinated intranasally three times at two-week intervals, and the immune response, as well as protection against influenza virus challenge, was measured. Antigen-specific IgG could be measured after two vaccinations, and a strong induction of IgA was observed in both nasal lavage fluid and lung tissue. Furthermore, influenza virus was non-detectable in nasal lavage or lung tissue three days after viral infection in vaccinated animals. Clinical signs of influenza disease were also prevented by the vaccination, indicating a vaccine-induced protective response. CONCLUSION: The intranasal OMV influenza vaccine candidate induces a strong mucosal and protective immune response.