References

Observations

Animals

Remarks

[30]

Attenuation (by treating mice with anti CD25) of Treg cells concomitant to BCG vaccination showed a positive, yet limited, impact on the protective capacity of this vaccine against M. Tuberculosis infection.

Mice

Tregs do not represent the major cause of the limited efficacy of BCG as a vaccine against tuberculosis.

[31]

BCG primed subjects showed better performance (as measured by IFN-γ response) followed by boosting with Vaccinia virus Ankara expressing the M.tuberculosis antigen 85A (MVA85A).This appears to be through the limiting effect (through reduced production of TGF-β) of MVA85A on the number of circulating CD4⁺CD25^hiFoxP3⁺ T cells.

Humans

This phenomenon indicates that Tregs affect the performance of BCG and MVA85A appears to be a potential adjuvant for BCG efficacy

[48]

BCG vaccinees were found to be associated with higher CD4⁺CD25^hiCD39⁺ T-cell levels in the periphery and a reduced capacity to produce IL-17A. However, on boosting with viral vector vaccine, consisting of MVA85A, induction of IL-17A-producing T cells were observed in the peripheral blood.

Humans

This phenomenon indicates that Tregs may affect the composition of vaccine-induced T-cells and that MVA85A appears to be a potential adjuvant for BCG efficacy

[49]

Priming with BCG followed by boosting with Modified Vaccinia virus Ankara expressing Antigen 85A (MVA85A) enhanced the BCG induced response by post boosting dropping down of CD25⁺CD39⁺ T regulatory cells along with reduction in consumption of ATP and increase in percentages IFN-γ and IL-17 double producing CD4⁺ T cells (Th1).

Humans

In vaccinated subjects, a positive relationship between extracellular ATP level and IFNγ⁺Th17 number again indicated that MVA85A appears to be a potential adjuvant for BCG efficacy through down regulation of CD39⁺ Tregs

[50]

Priming with BCG followed by boosting twice with AMM [Ag85B-Mpt64 (190-198)-Mtb8.4] showed best protective effect, against M.tuberculosis infection, among all groups (boosted once, twice and thrice), through induction of antigen-specific IFN-γ and IL-2 production and also down-regulation of CD4⁺ CD25⁺ FoxP3⁺ regulatory T cells.

Mice

AMM [Ag85B-Mpt64 (190-198)-Mtb8.4] appears to be a potential adjuvant for BCG efficacy

[51]

Heterologous immunization, using bacillus Calmette?Gue´rin (BCG) to prime and DNA-hsp 65 to boost or BCG to prime and culture filtrate proteins (CFP)-CpG to boost, was found to improve protection against M.tuberculosis infection. Improvement was through induction of higher ratio of CD4⁺ conventional T cells and CD4⁺T regulatory cells along with reduced lung morbidity.

Mice

DNA-hsp 65 (BCG/DNA-hsp 65) or BCG to prime and culture filtrate proteins (CFP)-CpG to boost (BCG/CFP-CpG) appears to be a potential adjuvant for BCG efficacy

[53]

Inhibition of CD4⁺ Tregs response by D4476 (4-[4-(2, 3-dihydro-1,4-benzodioxin-6-yl)-5-(2-pyridinyl)- 1H-imiodazol-2-yl]benzamide), a small molecule, improves efficacy of BCG against M. Tuberculosis infection. The efficacy is further enhanced on simultaneous inhibition of Th2 response.

Mice

Inhibition of Tregs response by small molecules could help in enhancing the efficacy of BCG