Publicación
Artículo científico (article).
Brucella melitensis Rev1Δwzm: placental pathogenesis studies and safety in pregnant ewes
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/355963
Digital.CSIC. Repositorio Institucional del CSIC
- Poveda-Urkixo, Irati
- Mena-Bueno, Sara
- Ramírez, Gustavo A.
- Zabalza-Baranguá, Ana
- Tsolis, Renee M.
- Grilló, María Jesús
One of the main causes of human brucellosis is Brucella melitensis infecting small ruminants. To date, Rev1 is the only vaccine successfully used to control ovine and caprine brucellosis. However, it is pathogenic for pregnant animals, resulting in abortions and vaginal and milk shedding, as well as being infectious for humans. Therefore, there is an urgent need to develop an effective vaccine that is safer than Rev1. In efforts to further attenuate Rev1, we recently used wzm inactivation to generate a rough mutant (Rev1Δwzm) that retains a complete antigenic O-polysaccharide in the bacterial cytoplasm. The aim of the present study was to evaluate the placental pathogenicity of Rev1Δwzm in trophoblastic cells, throughout pregnancy in mice, and in ewes inoculated in different trimesters of pregnancy. This mutant was evaluated in comparison with the homologous 16M∆wzm derived from a virulent strain of B. melitensis and the naturally rough sheep pathogen B. ovis. Our results show that both wzm mutants triggered reduced cytotoxic, pro-apoptotic, and pro-inflammatory signaling in Bewo trophoblasts, as well as reduced relative expression of apoptosis genes. In mice, both wzm mutants produced infection but were rapidly cleared from the placenta, in which only Rev1Δwzm induced a low relative expression of pro-apoptotic and pro-inflammatory genes. In the 66 inoculated ewes, Rev1Δwzm was safe and immunogenic, displaying a transient serological interference in standard RBT but not CFT S-LPS tests; this serological response was minimized by conjunctival administration. In conclusion, these results support that B. melitensis Rev1Δwzm is a promising vaccine candidate for use in pregnant ewes and its efficacy against B. melitensis and B. ovis infections in sheep warrants further study., This work was funded by Agencia Estatal de Investigación of the Ministerio de Ciencia, Innovación y Universidades (RTI2018-098658-B-C21 and PID2022-139200OB-C21) and Gobierno de Navarra (PT040-2018 and PT007-2019) research projects. IPU’s contract was granted by the Doctorados Industriales program of the Navarra government (2017-2019), cofounded by CSIC. SMB’s contracts were granted by the Garantía Juvenil CSIC-FEDER program (2016-2018) and by an UPNA pre-doctoral fellowship (2018–2022).
The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript., Peer reviewed
DOI: http://hdl.handle.net/10261/355963
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/355963
HANDLE: http://hdl.handle.net/10261/355963
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/355963
Ver en: http://hdl.handle.net/10261/355963
Digital.CSIC. Repositorio Institucional del CSIC
oai:digital.csic.es:10261/355963
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