Nanogram quantities of plasmid DNA encoding the rabies virus glycoprotein protect mice against lethal rabies virus infection

Abstract

Vaccination against virus infections has proven to be an effective strategy in the improvement of human health. In this study, we evaluated two plasmid DNA vaccines expressing the glycoprotein (G) gene of the challenge virus standard (CVS) rabies virus for their ability to elicit neutralizing antibody and protect BALB/cByJ mice against lethal rabies virus challenge. A single inoculation of 10 μg of plasmid DNA encoding G protected 100% of the intramuscularly (i.m.) vaccinated mice, and 0.1 μg of DNA protected 83% of the intradermally (i.d.) vaccinated mice. All mice that survived had serum anti-rabies virus neutralizing antibody titers ≥1:40 prior to virus challenge. The highest antibody titers were detected in mice that had been inoculated i.m. with 10–100 μg of DNA in regenerating muscle. The immunostimulant monophosphoryl lipid A enhanced the neutralizing antibody response of i.d.-vaccinated mice. Anti-rabies virus neutralizing antibody elicited by plasmid DNA vaccination cross-neutralized a global spectrum of rabies virus variants. These results indicate that DNA vaccines could be a solution for providing developing countries with an inexpensive vaccine that is simple to prepare, is highly efficacious and has excellent stability.