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Background  In pulmonary  Mycobacterium tuberculosis (Mtb)  infection, immune responses are delayed compared to other respiratory infections, so that antigen-specific cells are not detected in the lungs earlier than day 14. Even after parenteral immunization with Bacille Calmette Guerin (BCG) or a subunit vaccine, the immune response after  Mtb  challenge is only slightly accelerated and the kinetics of pulmonary  Mtb  growth do not differ between naïve and immunized animals up to day 14.    Methods and Findings  Mice were immunized intranasally with a recombinant adenovirus expressing mycobacterial antigen 85A (Ad85A), challenged by aerosol with  Mtb  and the kinetics of  Mtb  growth in the lungs measured. Intranasal immunization with Ad85A inhibits  Mtb  growth in the early phase of infection, up to day 8. Protection is sustained for at least 7 months and correlates with the presence of antigen-specific activated effector CD8 T cells in the lungs. Antigen 85A-specific T cells respond to antigen presenting cells from the lungs of mice immunized with Ad85A 23 weeks previously, demonstrating the persistence of antigen in the lungs.    Conclusions/Significance  Intranasal immunization with Ad85A can inhibit early growth of  Mtb  because it establishes a lung antigen depot and maintains an activated lung-resident lymphocyte population. We propose that an optimal immunization strategy for tuberculosis should aim to induce both lung and systemic immunity, targeting the early and late phases of  Mtb  growth.

Immunization of Mice with a Recombinant Adenovirus Vaccine Inhibits the Early Growth of Mycobacterium tuberculosis After Infection