A Novel, Safe, Non-Adjuvanted Alphavirus RNA Particle Vaccine Expressing the Rabies Virus Glycoprotein Induces a Three-Year Duration of Immunity in Dogs and Cats After a Single Vaccine Dose.

BACKGROUND/OBJECTIVES: To this day, rabies remains a significant global threat. This threat remains even with the availability of vaccines for humans, wildlife, and domestic animals, which are used as part of a series of interventions to attempt to control the infection and disease. The number of annual human deaths from rabies globally remains significant, with infections being mainly caused by domestic dogs. Although a number of vaccines exist for domestic animals, most contain inactivated rabies virus with adjuvants. METHODS: To investigate alternatives to conventional rabies vaccines for dogs and cats, we developed a novel, non-adjuvanted, low-volume (0.5 mL) vaccine, based on the Venezuelan equine encephalitis virus (VEEV) TC-83-derived RNA particle (RP) expressing the rabies glycoprotein (G). This novel vaccine combines the safety profile of a non-adjuvanted vaccine while inducing consistently high efficacy and an extended duration of immunity similar to that shown by adjuvanted vaccines. RESULTS: In multiple studies, we demonstrated that young kittens and puppies can be safely vaccinated without serious adverse effects. In graded dose experiments with cats and dogs, the RNA particle vaccine induced neutralizing levels of antibodies. Additionally, in vaccination/challenge studies, 100% protection from virulent rabies was demonstrated in excess of three years post-vaccination from a single dose at 12 weeks of age in both dogs and cats. The safety of the RP-Rabies vaccine in dogs and cats as young as twelve weeks of age was demonstrated in field safety studies using two vaccine serials formulated at a field dose. CONCLUSIONS: Data from these studies suggest that the RP-Rabies vaccine offers an excellent alternative to current vaccines combining the safety of a non-adjuvanted vaccine in a low-volume, single dose with the induction of an extended duration of immunity of at least three years in both dogs and cats.