Limits...
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 - Vaccine (2008)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital, Oxford OX3 7LJ, UK. helen.fletcher@ndm.ox.ac.uk

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.

Show MeSH

Related in: MedlinePlus

Treatment of PBMC with anti-IFN-γ antibodies increases the expression of TGF-β1 mRNA. IFN-γ can lead to a down-regulation in TGF-β1 signaling. Blocking IFN-γ leads to a significant increase in TGF-β1 mRNA expression in BCG primed subjects 4 weeks post-vaccination with MVA85A, *p = 0.016 (Wilcoxon).
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2631167&req=5

fig5: Treatment of PBMC with anti-IFN-γ antibodies increases the expression of TGF-β1 mRNA. IFN-γ can lead to a down-regulation in TGF-β1 signaling. Blocking IFN-γ leads to a significant increase in TGF-β1 mRNA expression in BCG primed subjects 4 weeks post-vaccination with MVA85A, *p = 0.016 (Wilcoxon).

Mentions: A possible mechanism for the reduction in TGF-β1 mRNA in the BCG primed group is that the higher level of antigen-specific IFN-γ in the BCG prime–MVA85A boost group favors the down-regulation of TGF-β1 signaling and mRNA production. Cells from five BCG primed subjects vaccinated with MVA85A were cultured with 85A peptides and IFN-γ blocking antibodies. Blocking IFN-γ gamma significantly increased TGF-β1 mRNA expression in these subjects (p = 0.016) (Fig. 5).


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 - Vaccine (2008)

Treatment of PBMC with anti-IFN-γ antibodies increases the expression of TGF-β1 mRNA. IFN-γ can lead to a down-regulation in TGF-β1 signaling. Blocking IFN-γ leads to a significant increase in TGF-β1 mRNA expression in BCG primed subjects 4 weeks post-vaccination with MVA85A, *p = 0.016 (Wilcoxon).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2631167&req=5

fig5: Treatment of PBMC with anti-IFN-γ antibodies increases the expression of TGF-β1 mRNA. IFN-γ can lead to a down-regulation in TGF-β1 signaling. Blocking IFN-γ leads to a significant increase in TGF-β1 mRNA expression in BCG primed subjects 4 weeks post-vaccination with MVA85A, *p = 0.016 (Wilcoxon).
Mentions: A possible mechanism for the reduction in TGF-β1 mRNA in the BCG primed group is that the higher level of antigen-specific IFN-γ in the BCG prime–MVA85A boost group favors the down-regulation of TGF-β1 signaling and mRNA production. Cells from five BCG primed subjects vaccinated with MVA85A were cultured with 85A peptides and IFN-γ blocking antibodies. Blocking IFN-γ gamma significantly increased TGF-β1 mRNA expression in these subjects (p = 0.016) (Fig. 5).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Churchill Hospital, Oxford OX3 7LJ, UK. helen.fletcher@ndm.ox.ac.uk

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.

Show MeSH
Related in: MedlinePlus