E1-deleted adenoviral vectors expressing the rabies virus glycoprotein rapidly induce protective titers of rabies virus neutralizing antibodies in adult and neonatal mice upon systemic or mucosal immunization. Pre-existing immunity in humans due to natural infections with common human serotypes of adenovirus such as the human serotype 5, most commonly used as a vaccine carrier can be circumvented by systemic immunization with a simian-origin adenovirus or by using the oral route of immunization. Virus neutralizing antibody titers can be enhanced by prime-boost regimens.