Boosting BCG vaccination with MVA85A down-regulates the immunoregulatory cytokine TGF-β1

In clinical trials recombinant-modified vaccinia virus Ankara expressing the Mycobacterium tuberculosis antigen 85A (MVA85A) induces approximately 10 times more effector T cells than any other recombinant MVA vaccine. We have found that in BCG primed subjects MVA85A vaccination reduces transforming growth factor beta 1 (TGF-β1) mRNA in peripheral blood lymphocytes and reduces TGF-β1 protein in the serum, but increases IFN-γ ELISPOT responses to the recall antigen SK/SD. TGF-β1 is essential for the generation of regulatory T cells and we see a correlation across vaccinees between CD4+CD25hiFoxP3+ cells and TGF-β1 serum levels. This apparent ability to counteract regulatory T cell effects suggests a potential use of MVA85A as an adjuvant for less immunogenic vaccines.