Protective immunity against Mycobacterium tuberculosis depends on the generation of a T<sub>H</sub>1-type cellular immune response, characterized by the secretion of interferon-γ (IFN-γ) from antigen-specific T cells. The induction of potent cellular immune responses by vaccination in humans has proven difficult. Recombinant viral vectors, especially poxviruses and adenoviruses, are particularly effective at boosting previously primed CD4<sup>+</sup> and CD8<sup>+</sup> T-cell responses against a number of intracellular pathogens in animal studies. In the first phase 1 study of any candidate subunit vaccine against tuberculosis, recombinant modified vaccinia virus Ankara (MVA) expressing antigen 85A (MVA85A) was found to induce high levels of antigen-specific IFN-γ-secreting T cells when used alone in bacille Calmette-Guérin (BCG)-naive healthy volunteers. In volunteers who had been vaccinated 0.5-38 years previously with BCG, substantially higher levels of antigen-specific IFN-γ-secreting T cells were induced, and at 24 weeks after vaccination these levels were 5-30 times greater than in vaccinees administered a single BCG vaccination. Boosting vaccinations with MVA85A could offer a practical and efficient strategy for enhancing and prolonging antimycobacterial immunity in tuberculosis-endemic areas.
McShane, H.; Pathan, A.A.; Sander, C.R.; Keating, S.M.; Gilbert, S.C.; Huygen, K.; Fletcher, H.A.; Hill, A.V. Recombinant modified vaccinia virus Ankara expressing antigen 85A boosts BCG-primed and naturally acquired antimycobacterial immunity in humans. Nature Medicine 10 (11) 1240-1244. [DOI: 10.1038/nm1128]