Limits...
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

Different vaccination regimes induced different responses to mycobacterial antigens.Determination of the secretion of IFNγ by whole blood cells, measured by ELISA, from animals vaccinated with BCG at week 0 and challenged with M. bovis at week 12; vaccination and challenge are indicated by arrows on the x axis. Group average of antigen-specific whole blood IFNγ secretion, expressed as OD 450nm, was corrected for background and evaluated at the weeks indicated on the x axis. Animal groups are indicated naïve controls (N.C.) (open rhomboid); SIM BCG/Ad85A (inverted open triangle); BCG e.b. (open triangle); BCG s.c. (open square); SIM BCG/BCG (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. Statistical significance is indicated as follows: * difference between BCG/Ad85A and N.C.; ^ indicates differences between BCG e.b. and N.C.; % indicates differences between BCG s.c. and N.C.; & indicates differences between BCG/BCG and N.C. One symbol indicates ρ<0.05.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4636221&req=5

pone.0142270.g001: Different vaccination regimes induced different responses to mycobacterial antigens.Determination of the secretion of IFNγ by whole blood cells, measured by ELISA, from animals vaccinated with BCG at week 0 and challenged with M. bovis at week 12; vaccination and challenge are indicated by arrows on the x axis. Group average of antigen-specific whole blood IFNγ secretion, expressed as OD 450nm, was corrected for background and evaluated at the weeks indicated on the x axis. Animal groups are indicated naïve controls (N.C.) (open rhomboid); SIM BCG/Ad85A (inverted open triangle); BCG e.b. (open triangle); BCG s.c. (open square); SIM BCG/BCG (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. Statistical significance is indicated as follows: * difference between BCG/Ad85A and N.C.; ^ indicates differences between BCG e.b. and N.C.; % indicates differences between BCG s.c. and N.C.; & indicates differences between BCG/BCG and N.C. One symbol indicates ρ<0.05.

Mentions: Fig 1 shows the antigen specific immune responses induced by different vaccination regimes, as determined by measurement of IFNγ with the Bovigam assay, following overnight culture of whole blood with mycobacterial antigens. Levels of PPD-B-induced IFNγ produced after BCG s.c., rose from week three onwards. At week 6 and 12, responses to PPD-B induced by BCG/Ad85A were higher than the responses observed in N.C. (ρ<0.05). In terms of kinetics, BCG s.c. induced responses to PPD-B at weeks 3 and 6 that were significantly different to those detected at week 0 (ρ<0.05); BCG/BCG and BCG/Ad85A also had responses to PPD-B at week 6 that were significantly different to those detected prior to vaccination at week 0 (ρ<0.05) (S1 Fig). Negligible levels of IFNγ were detected in naive control animals before challenge with bTB.


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)

Different vaccination regimes induced different responses to mycobacterial antigens.Determination of the secretion of IFNγ by whole blood cells, measured by ELISA, from animals vaccinated with BCG at week 0 and challenged with M. bovis at week 12; vaccination and challenge are indicated by arrows on the x axis. Group average of antigen-specific whole blood IFNγ secretion, expressed as OD 450nm, was corrected for background and evaluated at the weeks indicated on the x axis. Animal groups are indicated naïve controls (N.C.) (open rhomboid); SIM BCG/Ad85A (inverted open triangle); BCG e.b. (open triangle); BCG s.c. (open square); SIM BCG/BCG (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. Statistical significance is indicated as follows: * difference between BCG/Ad85A and N.C.; ^ indicates differences between BCG e.b. and N.C.; % indicates differences between BCG s.c. and N.C.; & indicates differences between BCG/BCG and N.C. One symbol indicates ρ<0.05.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0142270.g001: Different vaccination regimes induced different responses to mycobacterial antigens.Determination of the secretion of IFNγ by whole blood cells, measured by ELISA, from animals vaccinated with BCG at week 0 and challenged with M. bovis at week 12; vaccination and challenge are indicated by arrows on the x axis. Group average of antigen-specific whole blood IFNγ secretion, expressed as OD 450nm, was corrected for background and evaluated at the weeks indicated on the x axis. Animal groups are indicated naïve controls (N.C.) (open rhomboid); SIM BCG/Ad85A (inverted open triangle); BCG e.b. (open triangle); BCG s.c. (open square); SIM BCG/BCG (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. Statistical significance is indicated as follows: * difference between BCG/Ad85A and N.C.; ^ indicates differences between BCG e.b. and N.C.; % indicates differences between BCG s.c. and N.C.; & indicates differences between BCG/BCG and N.C. One symbol indicates ρ<0.05.
Mentions: Fig 1 shows the antigen specific immune responses induced by different vaccination regimes, as determined by measurement of IFNγ with the Bovigam assay, following overnight culture of whole blood with mycobacterial antigens. Levels of PPD-B-induced IFNγ produced after BCG s.c., rose from week three onwards. At week 6 and 12, responses to PPD-B induced by BCG/Ad85A were higher than the responses observed in N.C. (ρ<0.05). In terms of kinetics, BCG s.c. induced responses to PPD-B at weeks 3 and 6 that were significantly different to those detected at week 0 (ρ<0.05); BCG/BCG and BCG/Ad85A also had responses to PPD-B at week 6 that were significantly different to those detected prior to vaccination at week 0 (ρ<0.05) (S1 Fig). Negligible levels of IFNγ were detected in naive control animals before challenge with bTB.

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