title: Boosting BCG vaccination with MVA85A down-regulates the immunoregulatory cytokine TGF-beta1.
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.
authors.affiliation: Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital, Oxford OX3 7LJ, UK. helen.fletcher@ndm.ox.ac.uk
authors.forename: Helen A
authors.initials: HA
authors.lastname: Fletcher
authors.forename: Ansar A
authors.initials: AA
authors.lastname: Pathan
authors.forename: Tamara K
authors.initials: TK
authors.lastname: Berthoud
authors.forename: Susanna J
authors.initials: SJ
authors.lastname: Dunachie
authors.forename: Kathryn T
authors.initials: KT
authors.lastname: Whelan
authors.forename: Nicola C
authors.initials: NC
authors.lastname: Alder
authors.forename: Clare R
authors.initials: CR
authors.lastname: Sander
authors.forename: Adrian V S
authors.initials: AV
authors.lastname: Hill
authors.forename: Helen
authors.initials: H
authors.lastname: McShane
mesh_terms: D000217:Acyltransferases / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology*; D001500:BCG Vaccine / Q000276:immunology*; D015536:Down-Regulation; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D053773:Transforming Growth Factor beta1 / Q000097:blood / Q000235:genetics*; D032581:Tuberculosis Vaccines / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D001500:BCG Vaccine; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053773:Transforming Growth Factor beta1; D032581:Tuberculosis Vaccines; D007371:Interferon-gamma; D000217:Acyltransferases; C112580:antigen 85A, Mycobacterium tuberculosis