Gene immunization of mice with plasmid DNA expressing rabies virus glycoprotein

Gene immunization can be an effective vaccine strategy eliciting both humor al and cell-mediated immune responses. We constructed plasmid vectors expre ssing the full-length Vnukovo-32 rabies virus glycoprotein G under the cont rol of CMV IE promoter and enhancer, adenovirus tripartite leader sequences and poly A signal of SV40. The gene vaccines were evaluated for the abilit y to elicit neutralizing antibodies and to protect BALB/c mice against leth al rabies virus challenge. First, mice were injected intramuscularly (i.m.) into the left hind leg and by the intradermoplantar (i.d.p.) route with eq ual amounts of plasmid DNA (0.25-0.1 mg). Two weeks later, immunization was boosted with an additional dose of the DNA. The immunized mice were challe nged by intracerebral (i.c.) inoculation of CVS-27 (10-50 LD50) rabies viru s. All mice produced anti-rabies virus neutralizing antibodies with a titre of greater than or equal to 1:45 after immunization with 0.1-0.4 mg of DNA . In challenge experiments, 83 to 91.6% protection was observed. These resu lts confirm that a DNA vaccine could be a simple and effective solution for preventing the spread of rabies.