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

Vaccine. 2008 Sep 26;26(41):5269-75. doi: 10.1016/j.vaccine.2008.07.040. Epub 2008 Aug 3.

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.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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*

Substances

  • Antigens, Bacterial
  • BCG Vaccine
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Transforming Growth Factor beta1
  • Tuberculosis Vaccines
  • Interferon-gamma
  • Acyltransferases
  • antigen 85A, Mycobacterium tuberculosis