Selection and Testing of Recombinant CAV 2- Rabies Vaccine for Oral Immunization of Wildlife

Oral immunization of wildlife and stray dogs with live vaccines is the only effective method to control rabies in carnivore species worldwide. Because adenoviruses replicate on mucosal surfaces, they represent excellent vectors that can be administered both orally and intranasally. The nearly ideal vaccine vector for immunization of carnivores against rabies would be the canine adenovirus type 2 (CAV 2) virus. The CAV 2 vaccine is a very effective livemodified vaccine which has an excellent safety record and which is being used worldwide for the routine vaccination of dogs against both CAV 1 and CAV 2. Although this vaccine is usually administered subcutaneously, it is also effective when administered orally and may allow for limited animal to animal transmission. Previous phase I efforts demonstrated the initial proof of concept through successful construction and selection of CAV 2-RVG viruses followed by evaluation of safety and protective activity in laboratory animals. In this Phase II project we propose to continue evaluation of the vaccine candidate through optimization of virus growth and production of a research viral seed (RVS) stock, genetic and thermal stability studies, in vitro and in vivo safety studies, and safety and efficacy studies in target animals. It is likely that CAV2-RVG will be immunogenic by the oral route in target animals resulting protective immunity against rabies. A key concern to be addressed in this project is the safety of the recombinant virus in target and non-target animals.