This project deals with an investigation of the biology of rabies virus and its by-products, for the ultimate purpose of developing an effective vaccine for man and animals both for widespread prophylactic immunization and post-exposure treatment. Specific projects will include development of suitable tissue culture systems, of both mammalian and other species, for replication studies, for the genetic analysis of rabies strains and for the large- scale production of rabies virions and their by-products of infection produced in tissue culture, which should prove useful in definitive characterization of the virus structure. Since partially purified and concentrated virion preparations inactivated by UV or beta-propiolactone can be used as vaccinating agents in primates, the possibility of making a virion-free antigen preparation to be used as a vaccinating agent will also be explored. To evaluate vaccine efficacy and antiserum therapy in rabies, a systematic investigation of the immunopathology of the disease is proposed. Also, studies on the determination of the protein composition and the identity of individual proteins of rabies virus are being carried out.