TY - JOUR
T1 - Vaccine properties of Brucella melitensis 16MΔwzm and reactivation of placental infection in pregnant sheep
AU - Zabalza-Baranguá, A.
AU - Poveda-Urkixo, I.
AU - Mena-Bueno, S.
AU - Ramírez, G. A.
AU - De Bolle, X.
AU - Grilló, M. J.
N1 - Funding Information:
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).
Funding Information:
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 Proyecctos 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) ú. 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).
Publisher Copyright:
© 2023 Elsevier Ltd
PY - 2023/2/24
Y1 - 2023/2/24
N2 - 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.
AB - 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.
KW - Brucella melitensis
KW - Mice
KW - Placental infection
KW - Serological response
KW - Sheep
KW - Vaccine
UR - http://www.scopus.com/inward/record.url?scp=85146472774&partnerID=8YFLogxK
U2 - 10.1016/j.vaccine.2023.01.017
DO - 10.1016/j.vaccine.2023.01.017
M3 - Article
AN - SCOPUS:85146472774
SN - 0264-410X
VL - 41
SP - 1554
EP - 1566
JO - Vaccine
JF - Vaccine
IS - 9
ER -