The worldwide incidence of
rabies and the inability of currently used vaccination strategies to provide highly potent and cost-effective
therapy indicate the need for an improved
rabies vaccine. Thus,
DNA vaccine based on lysosome-targeted
glycoprotein of the rabies virus was evaluated in BALB/c mice. It imparted partial protection (60%) against challenge with 20 LD(50) of the challenge virus standard (CVS) strain of rabies virus. To improve the outcome of vaccination, to ultimately enhance the immune response, we investigated different routes for
DNA vaccine delivery, varied doses of
DNA, and the influence of adjuvant supplementation. The highest immune response pertaining to
IgG antibody titer, with a predominantly
IgG1/
IgG2a subclass distribution, effective cellular immunity, and a high level of rabies virus
neutralizing antibodies (RVNAs) was attained by the optimized
DNA vaccine formulation comprising intramuscular administration of 100 microg of
DNA vaccine supplemented with Emulsigen-D. In preexposure prophylaxis, a 3-dose regimen of this formulation generated a high RVNA titer (32 IU/ml) and conferred complete protection against challenge with 20 LD(50) of CVS. For postexposure efficacy analysis,
rabies was experimentally induced with 50 LD(50) of CVS. Subsequent
therapy with 5 doses of the formulation completely prevented
rabies in BALB/c mice, which maintained protective RVNA titers of 4 IU/ml. The World Health Organization recommended
rabies protective titer threshold is 0.5 IU/ml. Thus, this optimized
DNA vaccine formulation provides an avenue for preventing and controlling
rabies.