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• rAAV-G could induce the production of high levels of anti-RABV neutralizing antibodies. • rAAV-G could induce the Th1 and Th2 cellular immune response in mice. • High levels of neutralizing antibodies could remain for long periods of time in mice. • rAAV-G could provide strongly effective protection in mice infected with RABV. Rabies is a highly lethal infectious zoonosis caused by rabies virus (RABV), and the mortality rate is almost 100 % once clinical symptoms appear, which poses a huge threat to public health security across the many parts of the word. Vaccination is reported to be the most effective approach to prevent the disease. G protein is the only protein present on the surface of RABV, it also could induce humoral immunity to produce virus neutralizing antibodies (VNA) and stimulate T cells to produce cellular immunity. Adeno-associated viruses (AAVs) have been used as vectors for gene therapy of different human diseases for its low immunogenicity, high safety and long-term stable expression. To develop a safe and effective vaccine, recombinant AAVs containing different kind of G gene were constructed. After intramuscular (i.m.) immunization in mice, all of these rAAV-G vaccines could induce the production of high levels of VNA and effective cellular immune response. Consistently, all of the rAAV-G vaccines could provide protection against lethal RABV challenge. Our results shown that the rAAV-G vaccines could be potential candidates used in the control of RABV infection. In addition, rAAV-G as a vaccine has many advantages of low preparation cost, simple storage and transportation conditions (4 °C storage and transportation), simple immunization program (only one immunization) and so on. Thence, the rAAV-G vaccines could be potential candidates used in the control of RABV infection. [ABSTRACT FROM AUTHOR]