ABSTRACT
Against a pandemic of emerged infectious disease, COVID-19, new generation vaccines based on nucleic acids or recombinant viruses, which had not been used as vaccines in humans, have been inoculated and shown to be successful. They are, however, heat-labile and need a cold-chain including deep-freezers for storage and transportation. Vaccinia virus (VAC) vector vaccine (VACV) is a pioneer of new generation of vaccines constructed by using molecular biological technology. VACV, which has contributed to eradication of smallpox, has excellent characteristics of vaccinia virus such as a high heat-stability and long-lasting immunological effects. It is possible to distinguish the immunological responses of vaccination from those of natural infections. We started our developmental researches 35 years ago, using attenuated VAC strains established in Japan. In this article, we first describe the early researches of VACVs;development of two VACVs for Bovine leukemia virus and Rinderpest morbillivirus antigens and their protective immunity in large mammals, sheep and cows. Second, application of VACV is described;Rabies-VACV, which has already been licensed, used in the field in Europe and USA, and resulted in a prominent decrease of rabies. Then, current status of VACV research is described;non-replicating VACVs in mammalian cells have been developed as new-generation and ultimately-safe vaccines. We discuss the possibility of future application of VACV for wildlife.