Most of the recent HIV studies have focused on the clade B virus subtype. However, it is estimated that half the HIV patients in developing countries are infected with virus belonging to clade C. Therefore, a vaccine against HIV clade C is urgently required. In this study, we evaluate the immunogenicity and protective immunity of an adenovirus vector (Ad) in BALB/c mice and cynomolgus monkeys. We developed an HIV vaccine containing the HIV clade C gag gene using a replication-defective chimeric adenovirus type 5 (Ad5) vector incorporating Ad35 fiber (Ad5/35); this vector has exhibited low hepatotoxicity in animal models. We observed that immunization with the Ad5/35 vaccine generated heightened HIV-specific immune responses in both mice and monkeys. Furthermore, the Ad5/35 vector vaccine produced a cross-immunity against challenge with recombinant vaccinia viruses expressing HIV clade B gag. These results demonstrate that Ad5/35 vaccines expressing HIV clade C gag may be promising candidates for clinical trials.

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