Boosting BCG vaccination with MVA85A down-regulates the immunoregulatory cytokine TGF-beta1.
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.
Fletcher
Helen A
HA
Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital, Oxford OX3 7LJ, UK. helen.fletcher@ndm.ox.ac.uk
Pathan
Ansar A
AA
Berthoud
Tamara K
TK
Dunachie
Susanna J
SJ
Whelan
Kathryn T
KT
Alder
Nicola C
NC
Sander
Clare R
CR
Hill
Adrian V S
AV
McShane
Helen
H
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*
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