Immunogenicity and Protection against Mycobacterium caprae Challenge in Goats Vaccinated with BCG and Revaccinated after One Year
Abstract
1. Introduction
2. Materials and Methods
2.1. Animals, Vaccination Schedule and Experimental Infection
2.2. Ethics Statement
2.3. In Vitro IFN-γ Release Assay (IGRA)
2.4. Flow Cytometry and Intracellular IFN-γ Staining
2.5. Skin Tests
2.6. Post-Mortem Examination
2.7. M. caprae DNA Burden Assessment by qPCR
2.8. Data Analysis
3. Results
3.1. Immunological Responses after Vaccination and Revaccination
3.2. IFN-γ Responses After M. caprae Challenge
3.3. Clinical Signs and Body Condition Post-Challenge
3.4. Post-Mortem Findings
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
- World Health Organization. Global Tuberculosis Report 2019; World Health Organization: Geneva, Switzerland, 2019; Licence: CC BY-NC-SA 3.0 IGO; ISBN 9789241565714. [Google Scholar]
- Olea-Popelka, F.; Muwonge, A.; Perera, A.; Dean, A.S.; Mumford, E.; Erlacher-Vindel, E.; Forcella, S.; Silk, B.J.; Ditiu, L.; El Idrissi, A.; et al. Zoonotic tuberculosis in human beings caused by Mycobacterium bovis—A call for action. Lancet Infect. Dis. 2017, 17, e21–e25. [Google Scholar] [CrossRef]
- Arrieta-Villegas, C.; Perálvarez, T.; Vidal, E.; Puighibet, Z.; Moll, X.; Canturri, A.; Sevilla, I.A.; Espada, Y.; Juste, R.A.; Domingo, M.; et al. Efficacy of parenteral vaccination against tuberculosis with heat-inactivated Mycobacterium bovis in experimentally challenged goats. PLoS ONE 2018, 13, e0196948. [Google Scholar] [CrossRef] [PubMed]
- Cano-Terriza, D.; Risalde, M.A.; Rodríguez-Hernández, P.; Napp, S.; Fernández-Morente, M.; Moreno, I.; Bezos, J.; Fernández-Molera, V.; Sáez, J.L.; García-Bocanegra, I. Epidemiological surveillance of Mycobacterium tuberculosis complex in extensively raised pigs in the south of Spain. Prev. Vet. Med. 2018, 159, 87–91. [Google Scholar] [CrossRef] [PubMed]
- Buddle, B.M.; Vordermeier, H.M.; Chambers, M.A.; de Klerk-Lorist, L.M. Efficacy and safety of BCG vaccine for control of tuberculosis in domestic livestock and wildlife. Front. Vet. Sci. 2018, 5, 259. [Google Scholar] [CrossRef] [PubMed]
- Waters, W.R.; Palmer, M.V.; Buddle, B.M.; Vordermeier, H.M. Bovine tuberculosis vaccine research: Historical perspectives and recent advances. Vaccine 2012, 30, 2611–2622. [Google Scholar] [CrossRef]
- Pérez De Val, B.; Vidal, E.; Villarreal-Ramos, B.; Gilbert, S.C.; Andaluz, A.; Moll, X.; Martín, M.; Nofrarías, M.; McShane, H.; Vordermeier, H.M.; et al. A multi-antigenic adenoviral-vectored vaccine improves BCG-induced protection of goats against pulmonary tuberculosis infection and prevents disease progression. PLoS ONE 2013, 8, e81317. [Google Scholar] [CrossRef]
- Roy, A.; Tomé, I.; Romero, B.; Lorente-Leal, V.; Infantes-Lorenzo, J.A.; Domínguez, M.; Martín, C.; Aguiló, N.; Puentes, E.; Rodríguez, E.; et al. Evaluation of the immunogenicity and efficacy of BCG and MTBVAC vaccines using a natural transmission model of tuberculosis. Vet. Res. 2019, 50, 82. [Google Scholar] [CrossRef]
- Kipnis, A.; Irwin, S.; Izzo, A.A.; Basaraba, R.J.; Orme, I.M. Memory T Lymphocytes Generated by Mycobacterium bovis BCG Vaccination Reside within a CD4 CD44lo CD62 Ligandhi Population. Infect. Immun. 2005, 73, 7759–7764. [Google Scholar] [CrossRef]
- Orme, I.M.; Henao-Tamayo, M.I. Trying to see the forest through the trees: Deciphering the nature of memory immunity to Mycobacterium tuberculosis. Front. Immunol. 2018, 9, 461. [Google Scholar] [CrossRef]
- Thom, M.L.; McAulay, M.; Vordermeier, H.M.; Clifford, D.; Hewinson, R.G.; Villarreal-Ramos, B.; Hope, J.C. Duration of Immunity against Mycobacterium bovis following Neonatal Vaccination with Bacillus Calmette-Guérin Danish: Significant Protection against Infection at 12, but Not 24, Months. Clin. Vaccine Immunol. 2012, 19, 1254–1260. [Google Scholar] [CrossRef]
- Parlane, N.A.; Shu, D.; Subharat, S.; Wedlock, D.N.; Rehm, B.H.A.; De Lisle, G.W.; Buddle, B.M. Revaccination of cattle with bacille Calmette-Guérin two years after first vaccination when immunity has waned, boosted protection against challenge with Mycobacterium bovis. PLoS ONE 2014, 9, e106519. [Google Scholar] [CrossRef][Green Version]
- Vordermeier, H.M.; Jones, G.J.; Buddle, B.M.; Hewinson, R.G. Development of immune-diagnostic reagents to diagnose bovine tuberculosis in cattle. Vet. Immunol. Immunopathol. 2016, 181, 10–14. [Google Scholar] [CrossRef] [PubMed]
- Balseiro, A.; Altuzarra, R.; Vidal, E.; Moll, X.; Espada, Y.; Sevilla, I.A.; Domingo, M.; Garrido, J.M.; Juste, R.A.; Prieto, M.; et al. Assessment of BCG and inactivated Mycobacterium bovis vaccines in an experimental tuberculosis infection model in sheep. PLoS ONE 2017, 12, e0180546. [Google Scholar] [CrossRef] [PubMed]
- Pérez de Val, B.; Vidal, E.; López-Soria, S.; Marco, A.; Cervera, Z.; Martín, M.; Mercader, I.; Singh, M.; Raeber, A.; Domingo, M. Assessment of safety and interferon gamma responses of Mycobacterium bovis BCG vaccine in goat kids and milking goats. Vaccine 2016, 34, 881–886. [Google Scholar] [CrossRef] [PubMed]
- Pérez De Val, B.; López-Soria, S.; Nofrarías, M.; Martín, M.; Vordermeier, H.M.; Villarreal-Ramos, B.; Romera, N.; Escobar, M.; Solanes, D.; Cardona, P.J.; et al. Experimental model of tuberculosis in the domestic goat after endobronchial infection with Mycobacterium caprae. Clin. Vaccine Immunol. 2011, 18, 1872–1881. [Google Scholar] [CrossRef] [PubMed]
- Arrieta-Villegas, C.; Allepuz, A.; Grasa, M.; Martín, M.; Cervera, Z.; Mercader, I.; López-Soria, S.; Domingo, M.; Pérez de Val, B. Long-term efficacy of BCG vaccination in goat herds with a high prevalence of tuberculosis. Sci. Rep. 2020, 10, 20369. [Google Scholar] [CrossRef] [PubMed]
- Vidal, E.; Arrieta-Villegas, C.; Grasa, M.; Mercader, I.; Domingo, M.; Pérez de Val, B. Field evaluation of the efficacy of Mycobacterium bovis BCG vaccine against tuberculosis in goats. BMC Vet. Res. 2017, 13, 252. [Google Scholar] [CrossRef]
- Pathak, S.; Awuh, J.A.; Leversen, N.A.; Flo, T.H.; Åsjø, B. Counting mycobacteria in infected human cells and mouse tissue: A comparison between qPCR and CFU. PLoS ONE 2012, 7, e34931. [Google Scholar] [CrossRef]
- Wangoo, A.; Johnson, L.; Gough, J.; Ackbar, R.; Inglut, S.; Hicks, D.; Spencer, Y.; Hewinson, G.; Vordermeier, M. Advanced granulomatous lesions in Mycobacterium bovis-infected cattle are associated with increased expression of type I procollagen, gammadelta (WC1+) T cells and CD 68+ cells. J. Comp. Pathol. 2005, 133, 223–234. [Google Scholar] [CrossRef]
- Buddle, B.M.; Wards, B.J.; Aldwell, F.E.; Collins, D.M.; De Lisle, G.W. Influence of sensitisation to environmental mycobacteria on subsequent vaccination against bovine tuberculosis. Vaccine 2002, 20, 1126–1133. [Google Scholar] [CrossRef]
- Andersen, P.; Doherty, T.M. The success and failure of BCG—Implications for a novel tuberculosis vaccine. Nat. Rev. Microbiol. 2005, 3, 656–662. [Google Scholar] [CrossRef] [PubMed]
- Young, S.L.; Slobbe, L.; Wilson, R.; Buddle, B.M.; De Lisle, G.W.; Buchan, G.S. Environmental strains of Mycobacterium avium interfere with immune responses associated with Mycobacterium bovis BCG vaccination. Infect. Immun. 2007, 75, 2833–2840. [Google Scholar] [CrossRef] [PubMed]
- Whittaker, E.; Nicol, M.P.; Zar, H.J.; Tena-Coki, N.G.; Kampmann, B. Age-related waning of immune responses to BCG in healthy children supports the need for a booster dose of BCG in TB endemic countries. Sci. Rep. 2018, 8, 15309. [Google Scholar] [CrossRef]
- Buddle, B.M.; Wedlock, D.N.; Parlane, N.A.; Corner, L.A.L.; De Lisle, G.W.; Skinner, M.A. Revaccination of Neonatal Calves with Mycobacterium bovis BCG Reduces the Level of Protection against Bovine Tuberculosis Induced by a Single Vaccination. Infect. Immun. 2003, 71, 6411–6419. [Google Scholar] [CrossRef] [PubMed]
- Andersen, P.; Smedegaard, B. CD4+ T-cell subsets that mediate immunological memory to Mycobacterium tuberculosis infection in mice. Infect. Immun. 2000, 68, 621–629. [Google Scholar] [CrossRef] [PubMed]
- Sallusto, F.; Lenig, D.; Förster, R.; Lipp, M.; Lanzavecchia, A. Two subsets of memory T lymphocytes with distinct homing potentials and effector functions. Nature 1999, 401, 708–712. [Google Scholar] [CrossRef] [PubMed]
- Maggioli, M.F.; Palmer, M.V.; Thacker, T.C.; Vordermeier, H.M.; Waters, W.R. Characterization of effector and memory T cell subsets in the immune response to bovine tuberculosis in cattle. PLoS ONE 2015, 10, e0122571. [Google Scholar] [CrossRef]
- Blunt, L.; Hogarth, P.J.; Kaveh, D.A.; Webb, P.; Villarreal-Ramos, B.; Vordermeier, H.M. Phenotypic characterization of bovine memory cells responding to mycobacteria in IFNγ enzyme linked immunospot assays. Vaccine 2015, 33, 7276–7282. [Google Scholar] [CrossRef]
- Weir, R.E.; Gorak-Stolinska, P.; Floyd, S.; Lalor, M.K.; Stenson, S.; Branson, K.; Blitz, R.; Ben-Smith, A.; Fine, P.E.M.; Dockrell, H.M. Persistence of the immune response induced by BCG vaccination. BMC Infect. Dis. 2008, 8, 9. [Google Scholar] [CrossRef]
- Uzal, F.A.; Bodero, D.A.V.; Kelly, W.R.; Nielsen, K. Variability of serum antibody responses of goat kids to a commercial Clostridium perfringens epsilon toxoid vaccine. Vet. Rec. 1998. [Google Scholar] [CrossRef]
- Tizard, I.R. Chapter 17—Sheep and Goat Vaccines. In Vaccines for Veterinarians; Elsevier: Amsterdam, The Netherlands, 2020; pp. 215–224.e1. [Google Scholar] [CrossRef]
- Lacasta, D.; Ferrer, L.M.; Ramos, J.J.; González, J.M.; Ortín, A.; Fthenakis, G.C. Vaccination schedules in small ruminant farms. Vet. Microbiol. 2015, 181, 34–46. [Google Scholar] [CrossRef] [PubMed]
- Bezos, J.; Casal, C.; Puentes, E.; Díez-Guerrier, A.; Romero, B.; Aguiló, N.; de Juan, L.; Martín, C.; Domínguez, L. Evaluation of the immunogenicity and diagnostic interference caused by M. tuberculosis SO2 vaccination against tuberculosis in goats. Res. Vet. Sci. 2015, 103, 73–79. [Google Scholar] [CrossRef]
- van der Heijden, E.M.D.L.V.; Chileshe, J.; Vernooij, J.C.M.; Gortazar, C.; Juste, R.A.; Sevilla, I.; Crafford, J.E.; Rutten, V.P.M.G.; Michel, A.L. Immune response profiles of calves following vaccination with live BCG and inactivated Mycobacterium bovis vaccine candidates. PLoS ONE 2017, 12, e0188448. [Google Scholar] [CrossRef] [PubMed]
- Jones, G.J.; Whelan, A.; Clifford, D.; Coad, M.; Vordermeier, H.M. Improved skin test for differential diagnosis of bovine tuberculosis by the addition of Rv3020c-derived peptides. Clin. Vaccine Immunol. 2012, 19, 620–622. [Google Scholar] [CrossRef] [PubMed]
- Millington, K.A.; Fortune, S.M.; Low, J.; Garces, A.; Hingley-Wilson, S.M.; Wickremasinghe, M.; Kon, O.M.; Lalvani, A. Rv3615c is a highly immunodominant RD1 (Region of difference 1)-dependent secreted antigen specific for Mycobacterium tuberculosis infection. Proc. Natl. Acad. Sci. USA 2011, 108, 5730–5735. [Google Scholar] [CrossRef] [PubMed]
- Srinivasan, S.; Jones, G.; Veerasami, M.; Steinbach, S.; Holder, T.; Zewude, A.; Fromsa, A.; Ameni, G.; Easterling, L.; Bakker, D.; et al. A defined antigen skin test for the diagnosis of bovine tuberculosis. Sci. Adv. 2019, 5. [Google Scholar] [CrossRef] [PubMed]
Post-Mortem Parameter | Body Weight Change | Rectal Temperature | |||||
---|---|---|---|---|---|---|---|
W 3 | W 5 | W 7 | W 9 | W 3 | W 4 | W 5 | |
M. caprae CFU equivalents | −0.061 | −0.221 | −0.234 | −0.3035 | 0.234 | 0.27 | 0.336 |
Vol Lesions in LN | −0.414 * | −0.511 ** | −0.576 *** | −0.542 ** | 0.444 * | 0.428 * | 0.435 * |
Vol Lung Lesions | −0.319 | −0.482 ** | −0.587 *** | −0.692 *** | 0.277 | 0.456 * | 0.548 ** |
Animals with Extrapulmonary Lesions | Localization of Lesions | |||||
---|---|---|---|---|---|---|
Spleen | Liver | Ln Ms 1 | Kidney | Ln RF 2 | ||
BCG | 7/10 | 5 | 2 | 4 | 2 | 0 |
BCG-BCG | 7/10 | 6 | 2 | 4 | 1 | 4 |
Control | 9/10 | 8 | 4 | 8 | 4 | 1 |
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Arrieta-Villegas, C.; Vidal, E.; Martín, M.; Verdés, J.; Moll, X.; Espada, Y.; Singh, M.; Villarreal-Ramos, B.; Domingo, M.; Pérez de Val, B. Immunogenicity and Protection against Mycobacterium caprae Challenge in Goats Vaccinated with BCG and Revaccinated after One Year. Vaccines 2020, 8, 751. https://doi.org/10.3390/vaccines8040751
Arrieta-Villegas C, Vidal E, Martín M, Verdés J, Moll X, Espada Y, Singh M, Villarreal-Ramos B, Domingo M, Pérez de Val B. Immunogenicity and Protection against Mycobacterium caprae Challenge in Goats Vaccinated with BCG and Revaccinated after One Year. Vaccines. 2020; 8(4):751. https://doi.org/10.3390/vaccines8040751
Chicago/Turabian StyleArrieta-Villegas, Claudia, Enric Vidal, Maite Martín, Judit Verdés, Xavier Moll, Yvonne Espada, Mahavir Singh, Bernardo Villarreal-Ramos, Mariano Domingo, and Bernat Pérez de Val. 2020. "Immunogenicity and Protection against Mycobacterium caprae Challenge in Goats Vaccinated with BCG and Revaccinated after One Year" Vaccines 8, no. 4: 751. https://doi.org/10.3390/vaccines8040751
APA StyleArrieta-Villegas, C., Vidal, E., Martín, M., Verdés, J., Moll, X., Espada, Y., Singh, M., Villarreal-Ramos, B., Domingo, M., & Pérez de Val, B. (2020). Immunogenicity and Protection against Mycobacterium caprae Challenge in Goats Vaccinated with BCG and Revaccinated after One Year. Vaccines, 8(4), 751. https://doi.org/10.3390/vaccines8040751