An intranasal quadruple variant vaccine approach using SARS-CoV-2 and influenza A: Delta, Omicron, H1N1and H3N2

Influenza and SARS-CoV-2 viruses are both responsible for respiratory tract infections that have caused global outbreaks. Due to frequent mutations, the CDC recommends annual COVID-19 vaccination (CDC Staying Up to Date with COVID-19 Vaccines, 2025), and studies confirm the safety of co-administering it with the flu shot (CDC Getting a Flu Vaccine and Other Recommended Vaccines at the Same Time, 2025). A combination vaccine streamlines dual immunization, reducing the need for separate vaccinations. This study evaluates the immune response elicited by an intranasal microparticulate combination multivalent vaccine for Influenza and COVID-19. The intranasal route can generate mucosal antibodies that recognize and inhibit the virus at its point of entry. The nasal mucosa is highly vascularized, consisting of circulating immune cells that drain into lymphatic circulation to generate a systemic immune response. This non-invasive route of administration can also significantly benefit patients with needle phobia and vaccine hesitancy. The inactivated SARS-CoV-2 Omicron and Delta variants, along with the H1N1 and H3N2 variants of Influenza A were encapsulated into separate PLGA (co-polymer of lactic and glycolic acids) microparticle matrices utilizing a double emulsion method. The adjuvanted vaccine microparticles were administered to mice as one primary vaccination followed by one booster dose via the intranasal route. Serum and lung supernatant analysis revealed significantly higher antigen-specific IgA and IgG responses than controls. Isolated lymph nodes and spleens showed increased cytotoxic and helper T-cell activation. The intranasal vaccine effectively elicited a significant immune response which was comparable in relation to the intramuscular control vaccination. This supports the potential of an intranasal microparticulate combination vaccine as an effective, needle-free alternative for simultaneous immunization for Influenza and SARS-CoV-2.