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

• Published in: Vaccine 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 V S, McShane, Helen
• Format: Journal Article
• Language: English
• Published: Netherlands 26.09.2008
• Subjects: Acyltransferases - immunology; Adolescent; Adult; Antigens, Bacterial - immunology; BCG Vaccine - immunology; Down-Regulation; Female; Forkhead Transcription Factors - immunology; Humans; Interferon-gamma - immunology; Leukocytes, Mononuclear - immunology; Male; Middle Aged; Mycobacterium tuberculosis - immunology; Transforming Growth Factor beta1 - blood; Transforming Growth Factor beta1 - genetics; Tuberculosis Vaccines - immunology
• ISSN: 0264-410X
• DOI: 10.1016/j.vaccine.2008.07.040

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.