Defined Antigen Skin Test for Bovine Tuberculosis Retains Specificity on Revaccination With Bacillus Calmette–Guérin

The Bacillus Calmette–Guérin (BCG) vaccination provides partial protection against, and reduces severity of pathological lesions associated with bovine tuberculosis (bTB) in cattle. Accumulating evidence also suggests that revaccination with BCG may be needed to enhance the duration of immune protec...

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Main Authors: Saraswathi Subramanian, Sreenidhi Srinivasan, Kathiravan Ramaiyan Selvaraju, Priyadharshini Michael Vinoli, Suganya Selladurai, Boominathan Ramasamy, Karthik Kumaragurubaran, Douwe Bakker, Martin Vordermeier, Vivek Kapur, Dhinakar Raj Gopal
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-04-01
Series:Frontiers in Veterinary Science
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Online Access:https://www.frontiersin.org/articles/10.3389/fvets.2022.814227/full
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author Saraswathi Subramanian
Sreenidhi Srinivasan
Kathiravan Ramaiyan Selvaraju
Priyadharshini Michael Vinoli
Suganya Selladurai
Boominathan Ramasamy
Karthik Kumaragurubaran
Douwe Bakker
Martin Vordermeier
Martin Vordermeier
Vivek Kapur
Vivek Kapur
Dhinakar Raj Gopal
author_facet Saraswathi Subramanian
Sreenidhi Srinivasan
Kathiravan Ramaiyan Selvaraju
Priyadharshini Michael Vinoli
Suganya Selladurai
Boominathan Ramasamy
Karthik Kumaragurubaran
Douwe Bakker
Martin Vordermeier
Martin Vordermeier
Vivek Kapur
Vivek Kapur
Dhinakar Raj Gopal
author_sort Saraswathi Subramanian
collection DOAJ
description The Bacillus Calmette–Guérin (BCG) vaccination provides partial protection against, and reduces severity of pathological lesions associated with bovine tuberculosis (bTB) in cattle. Accumulating evidence also suggests that revaccination with BCG may be needed to enhance the duration of immune protection. Since BCG vaccine cross-reacts with traditional tuberculin-based diagnostic tests, a peptide-based defined antigen skin test (DST) comprising of ESAT-6, CFP-10, and Rv3615c to detect the infected among the BCG-vaccinated animals (DIVA) was recently described. The DST reliably identifies bTB-infected animals in experimental challenge models and in natural infection settings, and differentiated these from animals immunized with a single dose of BCG in both skin tests and interferon-gamma release assay (IGRA). The current investigation sought to assess the diagnostic specificity of DST in calves (Bos taurus ssp. taurus × B. t. ssp. indicus; n = 15) revaccinated with BCG 6 months after primary immunization. The results show that none of the 15 BCG-revaccinated calves exhibited a delayed hypersensitivity response when skin tested with DST 61 days post-revaccination, suggesting 100% diagnostic specificity (one-tailed lower 95% CI: 82). In contrast, 8 of 15 (diagnostic specificity = 47%; 95% CI: 21, 73) BCG-revaccinated calves were positive per the single cervical tuberculin (SCT) test using bovine tuberculin. Together, these results show that the DST retains its specificity even after revaccination with BCG and confirms the potential for implementation of BCG-based interventions in settings where test-and-slaughter are not economically or culturally feasible.
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spelling doaj.art-c565c0eef0c04c8695c57e2a04f8eb542022-12-22T02:51:43ZengFrontiers Media S.A.Frontiers in Veterinary Science2297-17692022-04-01910.3389/fvets.2022.814227814227Defined Antigen Skin Test for Bovine Tuberculosis Retains Specificity on Revaccination With Bacillus Calmette–GuérinSaraswathi Subramanian0Sreenidhi Srinivasan1Kathiravan Ramaiyan Selvaraju2Priyadharshini Michael Vinoli3Suganya Selladurai4Boominathan Ramasamy5Karthik Kumaragurubaran6Douwe Bakker7Martin Vordermeier8Martin Vordermeier9Vivek Kapur10Vivek Kapur11Dhinakar Raj Gopal12Translational Research Platform for Veterinary Biologicals, Centre for Animal Health Studies, Tamil Nadu Veterinary and Animal Sciences University, Chennai, IndiaThe Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA, United StatesTranslational Research Platform for Veterinary Biologicals, Centre for Animal Health Studies, Tamil Nadu Veterinary and Animal Sciences University, Chennai, IndiaTranslational Research Platform for Veterinary Biologicals, Centre for Animal Health Studies, Tamil Nadu Veterinary and Animal Sciences University, Chennai, IndiaTranslational Research Platform for Veterinary Biologicals, Centre for Animal Health Studies, Tamil Nadu Veterinary and Animal Sciences University, Chennai, IndiaTranslational Research Platform for Veterinary Biologicals, Centre for Animal Health Studies, Tamil Nadu Veterinary and Animal Sciences University, Chennai, IndiaCentral University Laboratory, Tamil Nadu Veterinary and Animal Sciences University, Chennai, IndiaTechnical Consultant and Independent Researcher, Lelystad, NetherlandsDepartment of Bacteriology, Animal and Plant Health Agency, Addlestone, United KingdomCentre for Bovine Tuberculosis, Institute for Biological, Environmental and Rural Sciences, University of Aberystwyth, Aberystwyth, United KingdomThe Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA, United StatesDepartment of Animal Science, The Pennsylvania State University, University Park, PA, United StatesDepartment of Animal Biotechnology, Madras Veterinary College, Tamil Nadu Veterinary and Animal Sciences University, Chennai, IndiaThe Bacillus Calmette–Guérin (BCG) vaccination provides partial protection against, and reduces severity of pathological lesions associated with bovine tuberculosis (bTB) in cattle. Accumulating evidence also suggests that revaccination with BCG may be needed to enhance the duration of immune protection. Since BCG vaccine cross-reacts with traditional tuberculin-based diagnostic tests, a peptide-based defined antigen skin test (DST) comprising of ESAT-6, CFP-10, and Rv3615c to detect the infected among the BCG-vaccinated animals (DIVA) was recently described. The DST reliably identifies bTB-infected animals in experimental challenge models and in natural infection settings, and differentiated these from animals immunized with a single dose of BCG in both skin tests and interferon-gamma release assay (IGRA). The current investigation sought to assess the diagnostic specificity of DST in calves (Bos taurus ssp. taurus × B. t. ssp. indicus; n = 15) revaccinated with BCG 6 months after primary immunization. The results show that none of the 15 BCG-revaccinated calves exhibited a delayed hypersensitivity response when skin tested with DST 61 days post-revaccination, suggesting 100% diagnostic specificity (one-tailed lower 95% CI: 82). In contrast, 8 of 15 (diagnostic specificity = 47%; 95% CI: 21, 73) BCG-revaccinated calves were positive per the single cervical tuberculin (SCT) test using bovine tuberculin. Together, these results show that the DST retains its specificity even after revaccination with BCG and confirms the potential for implementation of BCG-based interventions in settings where test-and-slaughter are not economically or culturally feasible.https://www.frontiersin.org/articles/10.3389/fvets.2022.814227/fullbovine tuberculosis (bTB)Bacillus Calmette-Guérin (BCG) vaccineDSTspecificityDIVA
spellingShingle Saraswathi Subramanian
Sreenidhi Srinivasan
Kathiravan Ramaiyan Selvaraju
Priyadharshini Michael Vinoli
Suganya Selladurai
Boominathan Ramasamy
Karthik Kumaragurubaran
Douwe Bakker
Martin Vordermeier
Martin Vordermeier
Vivek Kapur
Vivek Kapur
Dhinakar Raj Gopal
Defined Antigen Skin Test for Bovine Tuberculosis Retains Specificity on Revaccination With Bacillus Calmette–Guérin
Frontiers in Veterinary Science
bovine tuberculosis (bTB)
Bacillus Calmette-Guérin (BCG) vaccine
DST
specificity
DIVA
title Defined Antigen Skin Test for Bovine Tuberculosis Retains Specificity on Revaccination With Bacillus Calmette–Guérin
title_full Defined Antigen Skin Test for Bovine Tuberculosis Retains Specificity on Revaccination With Bacillus Calmette–Guérin
title_fullStr Defined Antigen Skin Test for Bovine Tuberculosis Retains Specificity on Revaccination With Bacillus Calmette–Guérin
title_full_unstemmed Defined Antigen Skin Test for Bovine Tuberculosis Retains Specificity on Revaccination With Bacillus Calmette–Guérin
title_short Defined Antigen Skin Test for Bovine Tuberculosis Retains Specificity on Revaccination With Bacillus Calmette–Guérin
title_sort defined antigen skin test for bovine tuberculosis retains specificity on revaccination with bacillus calmette guerin
topic bovine tuberculosis (bTB)
Bacillus Calmette-Guérin (BCG) vaccine
DST
specificity
DIVA
url https://www.frontiersin.org/articles/10.3389/fvets.2022.814227/full
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