An E1-deleted adenoviral recombinant derived from the chimpanzee serotype 6 expressing a codon-optimized truncated form of gag of human immunodeficiency virus type 1 (HIV-1) was tested for induction of a transgene product-specific CD8+ T cell response upon oral immunization of mice. The vector was shown to induce gag-specific CD8+ T cells detectable at moderate frequencies of approximately 0.5-1.0% in the spleens and to provide partial protection in a surrogate challenge model based on intraperitoneal (i.p.) infection of mice with a vaccinia virus recombinant expressing gag (VVgag) of HIV-1. Frequencies of gag-specific CD8+ T cells could be augmented by using a different, i.e., heterologous, vaccine carrier based on a distinct recombinant virus or an alternative adenoviral serotype expressing the same form of gag for oral or systemic-booster immunization.