Vaccine properties of Brucella melitensis 16MΔwzm and reactivation of placental infection in pregnant sheep
Brucellosis, a worldwide zoonotic disease, is endemic in many developing countries. Besides causing significant economic losses for the livestock industry, it has severe consequences for human health. In endemic regions, small ruminants infected by Brucella melitensis are the main source of human brucellosis. Rev1, the only vaccine currently recommended to control the disease in sheep and goats, has several drawbacks. Rough lipopolysaccharide (R-LPS) mutants have been tested as alternatives, but most lack efficacy. Those in the Wzm/Wzt system responsible for O-polysaccharide export to the periplasm have been proposed as promising vaccine candidates, although to date they have been scarcely investigated in the natural host. In the present work, we studied the biological properties of a 16MΔwzm in-frame deletion mutant, including its safety in pregnant mice and sheep. In mice, 16MΔwzm prevented placental and fetal infections before parturition and protected against B. melitensis and Brucella ovis infections. In sheep, 16MΔwzm was equally safe in lambs, rams, and non-pregnant ewes, inducing some transient Rose Bengal reactions (<7 weeks). The serological reactions occurred earlier and more strongly in pregnant than in non-pregnant ewes and were significantly reduced when conjunctival rather than subcutaneous vaccination was used. In ewes vaccinated at mid-pregnancy, 16MΔwzm was not shed in vaginal discharges during the pregnancy and did not induce abortions/stillbirths. However, some ewes showed a transitory reactivation of infection in placentas and/or milk at parturition, accompanied by a seroconversion in smooth LPS (S-LPS) and/or R-LPS tests. Overall, 16MΔwzm can be considered as a safe vaccine for lambs, rams, and non-pregnant ewes, but its use at mid-pregnancy should be avoided to prevent vaccine dissemination at parturition. If the efficacy results against B. melitensis and B. ovis observed in mice are confirmed by further studies in the natural host, 16MΔwzm could constitute a useful vaccine.
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Elsevier
2023-02-24
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Subjects: | Brucella melitensis, Vaccine, Serological response, Placental infection, Mice, Sheep, |
Online Access: | http://hdl.handle.net/10261/336022 |
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Brucella melitensis Vaccine Serological response Placental infection Mice Sheep Brucella melitensis Vaccine Serological response Placental infection Mice Sheep |
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Brucella melitensis Vaccine Serological response Placental infection Mice Sheep Brucella melitensis Vaccine Serological response Placental infection Mice Sheep Zabalza-Baranguá, Ana Poveda-Urkixo, Irati Mena Bueno, Sara Ramírez, Gustavo A. De Bolle, Xavier Grilló, María Jesús Vaccine properties of Brucella melitensis 16MΔwzm and reactivation of placental infection in pregnant sheep |
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Brucellosis, a worldwide zoonotic disease, is endemic in many developing countries. Besides causing significant economic losses for the livestock industry, it has severe consequences for human health. In endemic regions, small ruminants infected by Brucella melitensis are the main source of human brucellosis. Rev1, the only vaccine currently recommended to control the disease in sheep and goats, has several drawbacks. Rough lipopolysaccharide (R-LPS) mutants have been tested as alternatives, but most lack efficacy. Those in the Wzm/Wzt system responsible for O-polysaccharide export to the periplasm have been proposed as promising vaccine candidates, although to date they have been scarcely investigated in the natural host. In the present work, we studied the biological properties of a 16MΔwzm in-frame deletion mutant, including its safety in pregnant mice and sheep. In mice, 16MΔwzm prevented placental and fetal infections before parturition and protected against B. melitensis and Brucella ovis infections. In sheep, 16MΔwzm was equally safe in lambs, rams, and non-pregnant ewes, inducing some transient Rose Bengal reactions (<7 weeks). The serological reactions occurred earlier and more strongly in pregnant than in non-pregnant ewes and were significantly reduced when conjunctival rather than subcutaneous vaccination was used. In ewes vaccinated at mid-pregnancy, 16MΔwzm was not shed in vaginal discharges during the pregnancy and did not induce abortions/stillbirths. However, some ewes showed a transitory reactivation of infection in placentas and/or milk at parturition, accompanied by a seroconversion in smooth LPS (S-LPS) and/or R-LPS tests. Overall, 16MΔwzm can be considered as a safe vaccine for lambs, rams, and non-pregnant ewes, but its use at mid-pregnancy should be avoided to prevent vaccine dissemination at parturition. If the efficacy results against B. melitensis and B. ovis observed in mice are confirmed by further studies in the natural host, 16MΔwzm could constitute a useful vaccine. |
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Agencia Estatal de Investigación (España) |
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Agencia Estatal de Investigación (España) Zabalza-Baranguá, Ana Poveda-Urkixo, Irati Mena Bueno, Sara Ramírez, Gustavo A. De Bolle, Xavier Grilló, María Jesús |
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Brucella melitensis Vaccine Serological response Placental infection Mice Sheep |
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Zabalza-Baranguá, Ana Poveda-Urkixo, Irati Mena Bueno, Sara Ramírez, Gustavo A. De Bolle, Xavier Grilló, María Jesús |
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Zabalza-Baranguá, Ana |
title |
Vaccine properties of Brucella melitensis 16MΔwzm and reactivation of placental infection in pregnant sheep |
title_short |
Vaccine properties of Brucella melitensis 16MΔwzm and reactivation of placental infection in pregnant sheep |
title_full |
Vaccine properties of Brucella melitensis 16MΔwzm and reactivation of placental infection in pregnant sheep |
title_fullStr |
Vaccine properties of Brucella melitensis 16MΔwzm and reactivation of placental infection in pregnant sheep |
title_full_unstemmed |
Vaccine properties of Brucella melitensis 16MΔwzm and reactivation of placental infection in pregnant sheep |
title_sort |
vaccine properties of brucella melitensis 16mδwzm and reactivation of placental infection in pregnant sheep |
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Elsevier |
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2023-02-24 |
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http://hdl.handle.net/10261/336022 |
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dig-idab-es-10261-3360222023-09-28T12:18:43Z Vaccine properties of Brucella melitensis 16MΔwzm and reactivation of placental infection in pregnant sheep Zabalza-Baranguá, Ana Poveda-Urkixo, Irati Mena Bueno, Sara Ramírez, Gustavo A. De Bolle, Xavier Grilló, María Jesús Agencia Estatal de Investigación (España) Ministerio de Ciencia, Innovación y Universidades (España) Ministerio de Economía y Competitividad (España) Diputación Foral de Navarra Consejo Superior de Investigaciones Científicas (España) European Commission Universidad Pública de Navarra Brucella melitensis Vaccine Serological response Placental infection Mice Sheep Brucellosis, a worldwide zoonotic disease, is endemic in many developing countries. Besides causing significant economic losses for the livestock industry, it has severe consequences for human health. In endemic regions, small ruminants infected by Brucella melitensis are the main source of human brucellosis. Rev1, the only vaccine currently recommended to control the disease in sheep and goats, has several drawbacks. Rough lipopolysaccharide (R-LPS) mutants have been tested as alternatives, but most lack efficacy. Those in the Wzm/Wzt system responsible for O-polysaccharide export to the periplasm have been proposed as promising vaccine candidates, although to date they have been scarcely investigated in the natural host. In the present work, we studied the biological properties of a 16MΔwzm in-frame deletion mutant, including its safety in pregnant mice and sheep. In mice, 16MΔwzm prevented placental and fetal infections before parturition and protected against B. melitensis and Brucella ovis infections. In sheep, 16MΔwzm was equally safe in lambs, rams, and non-pregnant ewes, inducing some transient Rose Bengal reactions (<7 weeks). The serological reactions occurred earlier and more strongly in pregnant than in non-pregnant ewes and were significantly reduced when conjunctival rather than subcutaneous vaccination was used. In ewes vaccinated at mid-pregnancy, 16MΔwzm was not shed in vaginal discharges during the pregnancy and did not induce abortions/stillbirths. However, some ewes showed a transitory reactivation of infection in placentas and/or milk at parturition, accompanied by a seroconversion in smooth LPS (S-LPS) and/or R-LPS tests. Overall, 16MΔwzm can be considered as a safe vaccine for lambs, rams, and non-pregnant ewes, but its use at mid-pregnancy should be avoided to prevent vaccine dissemination at parturition. If the efficacy results against B. melitensis and B. ovis observed in mice are confirmed by further studies in the natural host, 16MΔwzm could constitute a useful vaccine. This work was funded by the Agencia Estatal de Investigación of the Ministerio de Ciencia, Innovación y Universidades of Spain (AGL2014-58795-C4-2-R and RTI2018-098658-B-C21) and Dirección General de Industria, Energía Proyectos Estratégicos S3 of Gobierno de Navarra, Spain (projects PT068-2018 and PT007-2019). IPU was contracted in the context of the Doctorados Industriales program of Gobierno de Navarra, co-funded by CSIC (2017-2020). SMB contracts were funded by the “Garantía Juvenil” program of CSIC-FEDER 2016-2018 and a predoctoral (2018-2019) fellowship of the Public University of Navarra (UPNA, Spain). Also, we thank the scientific advice of Professor Jean-Jacques Letesson; and the technical support of Sagrario Pérez, Elena San Miguel and Manuel Barrón (LCA-Navarra, Spain) as well as the staff of the subcontracted companies Maeva Servet-Visavet and Animalia (Spain). 2023-09-28T12:10:04Z 2023-09-28T12:10:04Z 2023-02-24 2023-09-28T12:10:04Z artículo doi: 10.1016/j.vaccine.2023.01.017 issn: 0264-410X Vaccine 41(9): 1554-1566 (2023) http://hdl.handle.net/10261/336022 #PLACEHOLDER_PARENT_METADATA_VALUE# #PLACEHOLDER_PARENT_METADATA_VALUE# info:eu-repo/grantAgreement/MINECO//AGL2014-58795-C4-2-R/ES/BRUCELLOSIS: TESTS DIAGNOSTICOS Y VACUNAS DIVA FRENTE A BRUCELLA OVIS Y BRUCELLA SUIS/ info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-098658-B-C21/ES/EL SISTEMA DE DOS COMPONENTES WZM%2FWZT EN BRUCELLA: ESTUDIOS MOLECULARES, INTERACCIONES PATOGENO-HOSPEDADOR EN GANADO OVINO Y APLICACIONES EN B. SUIS/ Publisher's version The underlying dataset has been published as supplementary material of the article in the publisher platform at http://dx.doi.org/10.1016/j.vaccine.2023.01.017 http://dx.doi.org/10.1016/j.vaccine.2023.01.017 Sí open application/pdf Elsevier |