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Protection Induced by Simultaneous Subcutaneous and Endobronchial Vaccination with BCG/BCG and BCG/Adenovirus Expressing Antigen 85A against Mycobacterium bovis in Cattle.

Dean GS, Clifford D, Whelan AO, Tchilian EZ, Beverley PC, Salguero FJ, Xing Z, Vordermeier HM, Villarreal-Ramos B - PLoS ONE (2015)

Bottom Line: The incidence of bovine tuberculosis (bTB) in the GB has been increasing since the 1980s.There was significantly reduced visible pathology in animals receiving the simultaneous BCG/BCG or BCG/Ad85 treatment compared to naïve controls.Furthermore, there were significantly fewer advanced microscopic granulomata in animals receiving BCG/Ad85A compared to naive controls.

View Article: PubMed Central - PubMed

Affiliation: TB Research Group, APHA Weybridge, Woodham Lane, New Haw, KT15 3NB, Surrey, United Kingdom.

ABSTRACT
The incidence of bovine tuberculosis (bTB) in the GB has been increasing since the 1980s. Immunisation, alongside current control measures, has been proposed as a sustainable measure to control bTB. Immunisation with Mycobacterium bovis bacillus Calmette-Guerin (BCG) has been shown to protect against bTB. Furthermore, much experimental data indicates that pulmonary local immunity is important for protection against respiratory infections including Mycobacterium tuberculosis and that pulmonary immunisation is highly effective. Here, we evaluated protection against M. bovis, the main causative agent of bTB, conferred by BCG delivered subcutaneously, endobronchially or by the new strategy of simultaneous immunisation by both routes. We also tested simultaneous subcutaneous immunisation with BCG and endobronchial delivery of a recombinant type 5 adenovirus expressing mycobacterial antigen 85A. There was significantly reduced visible pathology in animals receiving the simultaneous BCG/BCG or BCG/Ad85 treatment compared to naïve controls. Furthermore, there were significantly fewer advanced microscopic granulomata in animals receiving BCG/Ad85A compared to naive controls. Thus, combining local and systemic immunisation limits the development of pathology, which in turn could decrease bTB transmission.

No MeSH data available.


Related in: MedlinePlus

The comparative frequency of IFNγ secreting cells responding to mycobacterial antigens does not appear to be affected by different vaccination regimes.The frequency of IFNγ producers in PBMC, as determined by ELISpot, from animals immunised with BCG at week 0 and challenged with 2000 cfu M. bovis at week 12 was determined as indicated in materials and methods; immunisation and challenge are indicated by arrows on the x axis. IFNγ ELISpot was evaluated at the weeks indicated on the x axis, corrected for background and expressed as spot forming units (SFU) per 106/PBMC. No significant differences in the frequency of IFNγ secreting cells responding to PPD-B, Rv0288 or r85A was detected between the different vaccination regimes after vaccination or after infection. N.C. (open rhomboid); SIM BCG/Ad85A inverted triangle; SIM BCG/BCG (open triangle); BCG e.b. (open square); BCG s.c. (open circle). Error bars represent the standard error of the mean (SEM). Data were analysed using a using a Kruskal-Wallis test with Dunn’s multiple column post-test comparison.
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pone.0142270.g002: The comparative frequency of IFNγ secreting cells responding to mycobacterial antigens does not appear to be affected by different vaccination regimes.The frequency of IFNγ producers in PBMC, as determined by ELISpot, from animals immunised with BCG at week 0 and challenged with 2000 cfu M. bovis at week 12 was determined as indicated in materials and methods; immunisation and challenge are indicated by arrows on the x axis. IFNγ ELISpot was evaluated at the weeks indicated on the x axis, corrected for background and expressed as spot forming units (SFU) per 106/PBMC. No significant differences in the frequency of IFNγ secreting cells responding to PPD-B, Rv0288 or r85A was detected between the different vaccination regimes after vaccination or after infection. N.C. (open rhomboid); SIM BCG/Ad85A inverted triangle; SIM BCG/BCG (open triangle); BCG e.b. (open square); BCG s.c. (open circle). Error bars represent the standard error of the mean (SEM). Data were analysed using a using a Kruskal-Wallis test with Dunn’s multiple column post-test comparison.

Mentions: Fig 2 shows the frequency of IFNγ producing cells after vaccination and infection. None of the vaccination regimes induced responses to any of the antigens used greater than those observed in the non-vaccinated group, however animals vaccinated with BCG s.c. (ρ<0.001), SIM BCG/BCG (ρ<0.01) and SIM BCG/Ad85 (ρ<0.01) showed responses that were higher than those observed at week 0 (S2 Fig). After infection, as after vaccination, no differences were observed in the responses to mycobacteria antigens between the different treatment groups but BCG s.c. vaccinated animals showed responses to Rv0288 that were different to those observed at week 0 (ρ<0.05). At week 19, N.C. animals (ρ<0.05) and those vaccinated with BCG e.b. (ρ<0.01) or SIM BCG/Ad85 (ρ<0.05) showed responses to PPD-B that were different from those observed at week 0. Responses to PPD-B detectable at week 23 in BCG e.b. and SIM BCG/BCG vaccinated animals were different to those detected at week 0 (ρ<0.05).


Protection Induced by Simultaneous Subcutaneous and Endobronchial Vaccination with BCG/BCG and BCG/Adenovirus Expressing Antigen 85A against Mycobacterium bovis in Cattle.

Dean GS, Clifford D, Whelan AO, Tchilian EZ, Beverley PC, Salguero FJ, Xing Z, Vordermeier HM, Villarreal-Ramos B - PLoS ONE (2015)

The comparative frequency of IFNγ secreting cells responding to mycobacterial antigens does not appear to be affected by different vaccination regimes.The frequency of IFNγ producers in PBMC, as determined by ELISpot, from animals immunised with BCG at week 0 and challenged with 2000 cfu M. bovis at week 12 was determined as indicated in materials and methods; immunisation and challenge are indicated by arrows on the x axis. IFNγ ELISpot was evaluated at the weeks indicated on the x axis, corrected for background and expressed as spot forming units (SFU) per 106/PBMC. No significant differences in the frequency of IFNγ secreting cells responding to PPD-B, Rv0288 or r85A was detected between the different vaccination regimes after vaccination or after infection. N.C. (open rhomboid); SIM BCG/Ad85A inverted triangle; SIM BCG/BCG (open triangle); BCG e.b. (open square); BCG s.c. (open circle). Error bars represent the standard error of the mean (SEM). Data were analysed using a using a Kruskal-Wallis test with Dunn’s multiple column post-test comparison.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4636221&req=5

pone.0142270.g002: The comparative frequency of IFNγ secreting cells responding to mycobacterial antigens does not appear to be affected by different vaccination regimes.The frequency of IFNγ producers in PBMC, as determined by ELISpot, from animals immunised with BCG at week 0 and challenged with 2000 cfu M. bovis at week 12 was determined as indicated in materials and methods; immunisation and challenge are indicated by arrows on the x axis. IFNγ ELISpot was evaluated at the weeks indicated on the x axis, corrected for background and expressed as spot forming units (SFU) per 106/PBMC. No significant differences in the frequency of IFNγ secreting cells responding to PPD-B, Rv0288 or r85A was detected between the different vaccination regimes after vaccination or after infection. N.C. (open rhomboid); SIM BCG/Ad85A inverted triangle; SIM BCG/BCG (open triangle); BCG e.b. (open square); BCG s.c. (open circle). Error bars represent the standard error of the mean (SEM). Data were analysed using a using a Kruskal-Wallis test with Dunn’s multiple column post-test comparison.
Mentions: Fig 2 shows the frequency of IFNγ producing cells after vaccination and infection. None of the vaccination regimes induced responses to any of the antigens used greater than those observed in the non-vaccinated group, however animals vaccinated with BCG s.c. (ρ<0.001), SIM BCG/BCG (ρ<0.01) and SIM BCG/Ad85 (ρ<0.01) showed responses that were higher than those observed at week 0 (S2 Fig). After infection, as after vaccination, no differences were observed in the responses to mycobacteria antigens between the different treatment groups but BCG s.c. vaccinated animals showed responses to Rv0288 that were different to those observed at week 0 (ρ<0.05). At week 19, N.C. animals (ρ<0.05) and those vaccinated with BCG e.b. (ρ<0.01) or SIM BCG/Ad85 (ρ<0.05) showed responses to PPD-B that were different from those observed at week 0. Responses to PPD-B detectable at week 23 in BCG e.b. and SIM BCG/BCG vaccinated animals were different to those detected at week 0 (ρ<0.05).

Bottom Line: The incidence of bovine tuberculosis (bTB) in the GB has been increasing since the 1980s.There was significantly reduced visible pathology in animals receiving the simultaneous BCG/BCG or BCG/Ad85 treatment compared to naïve controls.Furthermore, there were significantly fewer advanced microscopic granulomata in animals receiving BCG/Ad85A compared to naive controls.

View Article: PubMed Central - PubMed

Affiliation: TB Research Group, APHA Weybridge, Woodham Lane, New Haw, KT15 3NB, Surrey, United Kingdom.

ABSTRACT
The incidence of bovine tuberculosis (bTB) in the GB has been increasing since the 1980s. Immunisation, alongside current control measures, has been proposed as a sustainable measure to control bTB. Immunisation with Mycobacterium bovis bacillus Calmette-Guerin (BCG) has been shown to protect against bTB. Furthermore, much experimental data indicates that pulmonary local immunity is important for protection against respiratory infections including Mycobacterium tuberculosis and that pulmonary immunisation is highly effective. Here, we evaluated protection against M. bovis, the main causative agent of bTB, conferred by BCG delivered subcutaneously, endobronchially or by the new strategy of simultaneous immunisation by both routes. We also tested simultaneous subcutaneous immunisation with BCG and endobronchial delivery of a recombinant type 5 adenovirus expressing mycobacterial antigen 85A. There was significantly reduced visible pathology in animals receiving the simultaneous BCG/BCG or BCG/Ad85 treatment compared to naïve controls. Furthermore, there were significantly fewer advanced microscopic granulomata in animals receiving BCG/Ad85A compared to naive controls. Thus, combining local and systemic immunisation limits the development of pathology, which in turn could decrease bTB transmission.

No MeSH data available.


Related in: MedlinePlus