Boosting BCG vaccination with MVA85A down-regulates the immunoregulatory cytokine TGF- beta 1

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...

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Published inVaccine Vol. 26; no. 41; pp. 5269 - 5275
Main Authors Fletcher, Helen A, Pathan, Ansar A, Berthoud, Tamara K, Dunachie, Susanna J, Whelan, Kathryn T, Alder, Nicola C, Sander, Clare R, Hill, Adrian VS, McShane, Helen
Format Journal Article
LanguageEnglish
Published 26.09.2008
Subjects
Mycobacterium tuberculosis
Vaccinia virus
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Summary: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- beta 1) mRNA in peripheral blood lymphocytes and reduces TGF- beta 1 protein in the serum, but increases IFN- gamma ELISPOT responses to the recall antigen SK/SD. TGF- beta 1 is essential for the generation of regulatory T cells and we see a correlation across vaccinees between CD4+CD25hiFoxP3+ cells and TGF- beta 1 serum levels. This apparent ability to counteract regulatory T cell effects suggests a potential use of MVA85A as an adjuvant for less immunogenic vaccines.
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ISSN:0264-410X
1873-2518
DOI:10.1016/j.vaccine.2008.07.040