DNA-based vaccination reduces the risk of lethal anaphylactic hypersensitivity in mice

Background: Anaphylactic hypersensitivity is the most serious clinical concern facing allergists. However, for the majority of anaphylactic hypersensitivities, avoidance is the only therapeutic option presently available. Objective: This study evaluated the effectiveness of primary gene and protein-immunostimulatory DNA vaccination in the prevention of anaphylactic hypersensitivity in a murine model. Methods: Female C3H/HeJ mice were immunized with a plasmid encoding beta-galactosidase (beta-gal) or beta-gal protein plus an immunostimulatory sequence oligodeoxynucleotide. The mice were then T-H2 sensitized to beta-gal by coinjection with alum and pertussis and then intravenously challenged with this model allergen, Results: Primary gene and protein-immunostimulatory DNA vaccination of subsequently T-H2-sensitized mice reduced the risk of death after anaphylactic challenge from 100% to 674 and 58%, respectively (P < .018 vs control mice). In addition, gene and protein-immunostimulatory DNA vaccination reduced postchallenge plasma histamine levels by greater than 4-fold (P < .05 vs control mite), Consistent with previous studies, these DNA-based vaccination strategies were further shown to blunt the development of T-H2-biased immune responses after allergen sensitization. Vaccination with protein alone, the experimental equivalent of a traditional immunotherapy reagent, provided no protection from anaphylaxis nor did it prevent the development of a T-H2-biased immune profile after allergen sensitization. Conclusion: The present series of experiments demonstrate that both gene vaccination and coimmunization with protein and immunostimulatory DNA are effective in attenuating the development of anaphylactic hypersensitivity in subsequently T-H2 sensitized mice.