RAPID DEVELOPMENT OF A VAXFECTIN®-ADJUVANTED DNA VACCINE ENCODING PANDEMIC SWINE-ORIGIN INFLUENZA A VIRUS (H1N1) HEMAGGLUTININ

Abstract

To support the initiation of a clinical trial in humans, the immunogenicity of a plasmid DNA vaccine encoding the hemagglutinin (HA) of the swine-origin influenza A (H1N1) virus (S-OIV) isolate, A/California/04/09, formulated with the adjuvant, Vaxfectin®, was administered intramuscularly to mice and rabbits at 100 μg and 1 mg DNA per injection, respectively, on Days 0 and 21. In hemagglutination inhibition (HI) assays using the reassortant virus, A/CA/07/09 NYMC X-179A, the titers for all animals were < 10 before vaccination. Three weeks after the first vaccination, 88% of mice and 75% of rabbits reached an HI titer of ≥ 40 with geometric mean titers (GMT) of 73 and 95, respectively. Two weeks after the second vaccination, 100% of mice and rabbits reached an HI titer of ≥ 40 with GMTs of 987 (range: 320–2560) for mice and 1522 (range: 640–2560) for rabbits. Sera from vaccinated mice and rabbits were also tested for HI titers against related S-OIV isolates. For mouse sera at Day 42, the HI GMTs against A/California/07/09, A/Texas/15/09 and A/Mexico/4108/09 were 905, 1280, and 1174, respectively, and for rabbit sera at Day 35 were 1522, 1280, and 1280, respectively. The results of this study indicate that the Vaxfectin®-adjuvanted S-OIV DNA vaccine is immunogenic and elicits HI antibodies that are reactive with related S-OIV.