Boosting BCG vaccination with MVA85A down-regulates the immunoregulatory cytokine TGF-beta1.


Fletcher, HA; Pathan, AA; Berthoud, TK; Dunachie, SJ; Whelan, KT; Alder, NC; Sander, CR; Hill, AV; McShane, H; (2008) Boosting BCG vaccination with MVA85A down-regulates the immunoregulatory cytokine TGF-beta1. Vaccine, 26 (41). pp. 5269-75. ISSN 0264-410X DOI: https://doi.org/10.1016/j.vaccine.2008.07.040

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Abstract

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-beta1) mRNA in peripheral blood lymphocytes and reduces TGF-beta1 protein in the serum, but increases IFN-gamma ELISPOT responses to the recall antigen SK/SD. TGF-beta1 is essential for the generation of regulatory T cells and we see a correlation across vaccinees between CD4+CD25hiFoxP3+ cells and TGF-beta1 serum levels. This apparent ability to counteract regulatory T cell effects suggests a potential use of MVA85A as an adjuvant for less immunogenic vaccines.

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Immunology and Infection
PubMed ID: 18682270
Web of Science ID: 260148900008
URI: http://researchonline.lshtm.ac.uk/id/eprint/1217110

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