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Protection and diagnostic interference induced by heat-inactivated, phage-inactivated and live vaccine prototypes against animal tuberculosis Fernández Veiga, Leire Fuertes, Miguel Geijo, María V. Elguezabal, Natalia Serrano-Mestre, Jose L. Vázquez-Iniesta, Lucía Prados-Rosales, Rafael Michelet, Lorraine Boschiroli, Maria Laura Pérez de Val, Bernat Jones, Gareth J. Juste, Ramón A. Garrido, Joseba M. Sevilla, Iker A. Producció Animal Sanitat Animal Introduction: Vaccination emerges as a promising cost-eective tool to reduce the impact and spread of animal tuberculosis, especially in regions where testand-slaughter eradication strategy is socioeconomically unfeasible or unfruitful for dierent reasons, provided it is safe, e cacious and compatible with diagnosis. Methods: In this study, we preliminarily evaluated the diagnostic interference (using guinea pigs) and the protective e cacy (using mice) of three heatinactivated, three phage-inactivated and one live attenuated vaccine prototypes prepared from M. bovis, M. caprae, and M. microti. Results and discussion: Phage-inactivation killed almost all (96.41–99.92%) bacteria to be included in vaccines and filtering was used to remove the remaining viable cells. All the assayed vaccines induced skin test reactions in response to bovine tuberculin, but they were smaller in the phage-inactivated vaccine groups. All the vaccines were diagnosis-compatible with defined skin test antigens based on ESAT-6, CFP-10, and Rv3615c. In contrast with the rest of prototypes, vaccination with heat- and phage-inactivated M. microti did not prompt the production of detectable anti-MPB70+MPB83 antibodies. Mean bacterial burden was lower in all vaccinated groups in comparison with the control, being significantly reduced in the lungs of the heat-inactivated M. microti and M. caprae and phage-inactivated M. caprae groups. Considering both diagnostic interference and protection collectively, the heat-inactivated M. microti vaccine showed the best performance. Further studies to evaluate these vaccines and to improve phage-driven inactivation are warranted. 2025-07-21 info:eu-repo/semantics/article Fernández-Veiga, Leire, Miguel Fuertes, María V Geijo, Natalia Elguezabal, Jose L Serrano-Mestre, Lucía Vázquez-Iniesta, Rafael Prados-Rosales, Bernat Pérez de Val, et al. 2025. “Protection and Diagnostic Interference Induced by Heat-inactivated, Phage-inactivated and Live Vaccine Prototypes Against Animal Tuberculosis.” Frontiers in Veterinary Science 12 (July). https://doi.org/10.3389/fvets.2025.1620497. 2297-1769 http://hdl.handle.net/20.500.12327/4808 https://doi.org/10.3389/fvets.2025.1620497 eng Frontiers in Veterinary Science MICINN/Programa Estatal de generación del conocimiento y fortalecimiento científico y tecnológico del sistema I+D+I/PID2019- 105155RB-C33/ES/DEVELOPMENT OF INACTIVATED VACCINE PROTOTYPES FOR THE CONTROL OF TB IN DOMESTIC ANIMALS AND ASSESSMENT OF THE INTEREFERENCE CAUSED BY NON TUBERCULOUS ORGANISMS ON ITS DIAGNOSI/ MICINN/Programa Estatal para Impulsar la Investigación Científico-Técnica y su Transferencia/PID2022-142939OR-C21/ES/DESARROLLO DE NUEVOS ABORDAJES DE VACUNACION MUCOSAL Y PARENTERAL FRENTE A LA TUBERCULOSIS ANIMAL Y EVALUACION DE SUS EFECTOS EN LOS MODELOS DE TUBERCULOSIS INTRANASAL DE RATO/ EC/INTERREG-POCTEFA/EFA115-01/EU/Red transpirenaica de investigación y desarrollo de herramientas innovadoras para el control de la tuberculosis animal/INNOTUB II FEDER/ / /EU/ / MICINN/Programa Estatal de generación del conocimiento y fortalecimiento científico y tecnológico del sistema I+D+I/PID2019-110240RB-I00/ES/IDENTIFICACION DE VULNERABILIDADES EN MYCOBACTERIUM TUBERCULOSIS A TRAVES DE LA DISECCION GENETICA Y QUIMICA DEL PROCESO DE VESICULACION/ MICINN/Programa Estatal para Impulsar la Investigación Científico-Técnica y su Transferencia/PID2022-136611OB-I00/ES/ IDENTIFICACION DE VULNERABILIDADES EN MYCOBACTERIUM TUBERCULOSIS A TRAVES DE LA DISECCION GENETICA Y QUIMICA DEL PROCESO DE VESICULACION/ http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess Attribution 4.0 International Frontiers Media