Rabies is a zoonotic and progressive viral disease in warm-blooded animals including human that is almost always fatal following the onset of clinical symptoms. Increasing evidence indicated that vaccination is an effective strategy for preventing rabies in the host reservoir. During the last 50 years, many attempts have been made to establish and develop rabies vaccines, aiming at preventing or controlling rabies animals and human. In this respect, first generation rabies vaccines including attenuated live vaccine and inactivated rabies have been characterized and evaluated in vitro and in vivo. To overcome the limitations of conventional rabies vaccines and improve potential immunogenicity and clinical efficacy, new-generation rabies vaccines including recombinant vaccines, viral vector vaccines, cell cultures vaccines, adjuvant vaccines, and DNA and RNA-based vaccines, as well as chimeric vaccines have been explored. So far, however, there has been little discussion about the immunogenicity, efficacy, and safety of rabies vaccines. Herein, this comprehensive review attempts to put together in vitro and in vivo studies, focusing on all types of rabies vaccines and gives an overview of their immunogenicity and efficacy. Finally, this review also assesses the clinical efficacy of rabies vaccines in clinical trials.
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