Subcutaneous administration of modified vaccinia virus Ankara expressing an Ag85B-ESAT6 fusion protein, but not an adenovirus-based vaccine, protects mice against intravenous challenge with Mycobacterium tuberculosis.

Recombinant virus-based tuberculosis (TB) vaccines that are strongly immunogenic and elicit robust cellular immunity are considered ideal vaccine candidates. Here, we engineered a poxvirus-based vaccine, MVA85B-E6, and an adenovirus-based vaccine, AD85B-E6, both of which express the fusion protein Ag85B-ESAT6. Subcutaneous vaccination of AD85B-E6 generated strong interferon (IFN)-γ production by both CD4 and CD8 T cells and CD8 cytotoxic T lymphocyte activity; these results indicate that strong T-helper type 1 immune responses were elicited in mice, which is in contrast to the moderate responses induced by vaccination with MVA85B-E6. However, MVA85B-E6 given subcutaneously led to levels of protection comparable with that induced by the bacillus Calmette-Guérin vaccine in the lungs and spleens, whereas AD85B-E6 given subcutaneously did not show any protective efficacy after intravenous challenge of BALB/c mice with Mycobacterium tuberculosis H37Rv. Our study emphasizes that more efficient biomarkers for vaccine efficacy and more appropriate routes of vaccine administration are necessary for the development of a successful TB vaccine.