We developed a universal influenza (UFlu) DNA vaccine to protect from annual influenza and future influenza variants with pandemic potential encoding HA stem or long alpha helix (LAH), the M2e consensus sequences from human, swine and avian strains to elicit broad protective antibody and nucleoprotein to induce protective T cell responses. We co-delivered genetic adjuvants encoding IL-12 to enhance T cell responses and the heat labile enterotoxin from E. Coli (LT) that we previously showed increases DNA vaccine induction of mucosal immune responses when delivered by gene gun into the epidermis of the skin and induces protective levels of immune responses in large animals and humans with very low doses of DNA (< 20 micrograms/dose). In mice, UFlu induced broad antibody and T cell responses, protection from representative influenza viruses, and superior protection vs. a strain-matched inactivated vaccine. In macaques, GG delivery of UFlu on weeks 0, 6, 19, and 43 induced robust HA and M2e antibody. mucosal and systemic NP-specific T cell responses in blood and lungs and protection from clinical disease after challenge with an H3N2 strain (A/Texas/71/2017) that is moderately virulent in macaques and after re-challenge with the highly virulent pandemic H1N1 strain A/California/04/2009. Peak viral loads in bronchoalveolar lavages at 3 days post-challenge were 2-3 Logs lower than in control macaques challenged with the same viruses. UFlu is being advanced to phase I human trials using a clinical gene gun (MACH-1TM) engineered by Orlance, Inc with innovations that are user friendly and increase penetration and distribution of the DNA/gold particles. When compared to legacy gene guns, MACH-1 improves local gene/antigen expression and immunogenicity and can deliver either DNA or RNA vaccines. Together, these studies support clinical development of a MACH-1 GG-delivered universal influenza DNA vaccine.
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A universal influenza DNA vaccine delivered via needle-free gene gun induces broad mucosal immunity against diverse influenza viruses in mice and nonhuman primates
Published:
09 March 2026
by MDPI
in Viruses 2026 – New Horizons in Virology
session Antiviral Therapeutics, Vaccines, and Host Defenses
Abstract:
Keywords: influenza; universal influenza vaccine; DNA vaccine; mucosal immunity; gene gun; nonhuman primates
