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

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.

This study evaluated the effectiveness of primary gene and protein-immunostimulatory DNA vaccination in the prevention of anaphylactic hypersensitivity in a murine model.

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.

Primary gene and protein-immunostimulatory DNA vaccination of subsequently T(H2)-sensitized mice reduced the risk of death after anaphylactic challenge from 100% to 67% 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 mice). 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.

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.