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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.

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Immune responses to the recall antigen SK/SD are increased at both weeks 1 and 12 in BCG primed subjects vaccinated with MVA85A (n = 9) (Wilcoxon). Box and whisker plots showing median, 25th and 75th percentiles.
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fig2: Immune responses to the recall antigen SK/SD are increased at both weeks 1 and 12 in BCG primed subjects vaccinated with MVA85A (n = 9) (Wilcoxon). Box and whisker plots showing median, 25th and 75th percentiles.

Mentions: To determine if the reduction in TGF-β1 serum protein could lead to a non-specific enhancement of effector T cell responses in vaccinated subjects IFN-γ ELISPOT responses to the recall antigen SK/SD were determined at weeks 0, 1, 4 and 12. SK/SD responses were significantly enhanced in BCG primed subjects at week 1 (median = 292 SFC/million) returned to baseline at week 4 (median = 107 SFC/million) and were enhanced again at week 12 post-vaccination with MVA85A (median = 307 SFC/million) (Fig. 2). This bi-modal increase in the SK/SD ELISPOT response seems to be the inverse of that seen with TGF-β1 protein in the serum. SK/SD responses were unchanged following vaccination with either BCG alone or MVA85A alone (data not shown).


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)

Immune responses to the recall antigen SK/SD are increased at both weeks 1 and 12 in BCG primed subjects vaccinated with MVA85A (n = 9) (Wilcoxon). Box and whisker plots showing median, 25th and 75th percentiles.
© Copyright Policy
Related In: Results  -  Collection

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

fig2: Immune responses to the recall antigen SK/SD are increased at both weeks 1 and 12 in BCG primed subjects vaccinated with MVA85A (n = 9) (Wilcoxon). Box and whisker plots showing median, 25th and 75th percentiles.
Mentions: To determine if the reduction in TGF-β1 serum protein could lead to a non-specific enhancement of effector T cell responses in vaccinated subjects IFN-γ ELISPOT responses to the recall antigen SK/SD were determined at weeks 0, 1, 4 and 12. SK/SD responses were significantly enhanced in BCG primed subjects at week 1 (median = 292 SFC/million) returned to baseline at week 4 (median = 107 SFC/million) and were enhanced again at week 12 post-vaccination with MVA85A (median = 307 SFC/million) (Fig. 2). This bi-modal increase in the SK/SD ELISPOT response seems to be the inverse of that seen with TGF-β1 protein in the serum. SK/SD responses were unchanged following vaccination with either BCG alone or MVA85A alone (data not shown).

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