New mouse model for dengue virus vaccine testing

Several dengue (DEN) virus vaccines are in development; however, the lack o f a reliable small animal model in which to test them is a major obstacle. Because evidence suggests that interferon (IFN) is involved in the human an ti-DEN virus response, we tested mice deficient in their IFN functions as p otential models. Intraperitoneally administered mouse-adapted DEN 2 virus w as uniformly lethal in AG129 mice (which lack alpha/beta IFN and gamma IFN receptor genes), regardless of age. Immunized mice were protected from viru s challenge, and survival times increased following passive transfer of ant i-DEN polyclonal antibody. These results demonstrate that AG129 mice are a promising small animal model for DEN virus vaccine trials.