Recombinant virus-vectored TB vaccines represent the most promising vaccine platform for boosting the protective immunity mediated by parenteral BCG prime immunization. A major advantage associated with virus-vectored vaccines is that they are potent respiratory mucosa-deliverable vaccines. A recombinant replication-deficient adenoviral (Ad) vector was engineered to express Mycobacterium tuberculosis (M.tb) Ag85A. Single administration of this Ad vaccine via the intranasal, but not intramuscular, route provided potent immune protection from pulmonary M.tb challenge. Respiratory mucosal boosting immunization with Ad vaccine was effective in enhancing T-cell activation and immune protection following parenteral DNA or BCG prime immunization. We have also recently developed a recombinant vesicular stomatitis virus-vectored (VSV) TB vaccine. Ad and VSV vector systems will be complementary to each other for BCG prime-virus vaccine boost immunization protocols.