Recombinant modified vaccinia virus Ankara expressing antigen 85A boosts BCG-primed and naturally acquired antimycobacterial immunity in humans

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Abstract
Protective immunity against Mycobacterium tuberculosis depends on the generation of a TH1-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+ and CD8+ T-cell responses against a number of intracellular pathogens in animal studies1,2,3,4,5,6,7. 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.
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