Conjunctival administration of H38ΔwbkF rough vaccine as an effective strategy to protect against Brucella ovis infection while minimizing serological interference

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dc.contributor.authorLópez Fernández, Nerea
dc.contributor.authorAndrés Barranco, Sara
dc.contributor.authorMiguel López, María Jesús de
dc.contributor.authorZúñiga Ripa, Amaia
dc.contributor.authorElizalde Bielsa, Aitor
dc.contributor.authorSalvador Bescós, Miriam
dc.contributor.authorIriarte, Maite
dc.contributor.authorBarberán Pelegrín, Montserrat
dc.contributor.authorBlasco Martínez, José María
dc.contributor.authorMoriyón Uria, Ignacio
dc.contributor.authorConde Álvarez, Raquel
dc.contributor.authorMuñoz Álvaro, Pilar María
dc.contributor.orcidAndrés Barranco, Sara [0000-0002-4127-234X]
dc.contributor.orcidMuñoz Álvaro, Pilar María [0000-0002-7970-4929]
dc.date.accessioned2026-03-12T11:23:47Z
dc.date.available2026-03-12T11:23:47Z
dc.date.issued2026-03-08
dc.date.updated2026-03-10T09:04:35Z
dc.description.abstractSheep brucellosis is a reproductive disease caused by Brucella melitensis and B. ovis, Gram-negative bacteria that differ in surface antigens: B. melitensis carries a smooth (S) lipopolysaccharide (LPS) with a characteristic O-polysaccharide (O-PS), while B. ovis bears a rough (R) LPS lacking O-PS. Only the former is zoonotic and of public health concern, but both cause significant economic losses, thus requiring effective vaccines. The sole vaccine available, B. melitensis Rev1, protects against both infections but induces antibodies detected by S-LPS-based tests used for B. melitensis surveillance. Since controlling this zoonotic species is a priority, Rev1 is banned in B. melitensis-free areas. Consequently, B. ovis (detected by R-LPS-based tests) remains endemic or re-emerges, and an R brucellosis vaccine is needed. Previously, we demonstrated that subcutaneous vaccination with B. melitensis R mutant H38ΔwbkF protects rams against B. ovis similarly to Rev1, without interfering in the official S-LPS-based Rose Bengal and Complement Fixation tests. However, H38ΔwbkF elicits R-LPS antibodies that interfere with B. ovis tests. Here, we explored two strategies to minimize this interference: (i) altering H38ΔwbkF relevant diagnostic epitopes by constructing wadB and wadC mutants deleted in sugars of the R-LPS core tetrasaccharide branch; and (ii) administering H38ΔwbkF conjunctivally, a route known to reduce antibody responses to S brucellosis vaccines. While the core-defective mutants were over-attenuated and failed to protect mice, the conjunctival route preserved H38ΔwbkF efficacy in rams and significantly reduced serological interference. Conjunctival H38ΔwbkF vaccine is thus a suitable tool for B. ovis eradication in B. melitensis-free areas.
dc.description.peerreviewedNo
dc.description.sponsorshipEsta investigación se ha llevado a cabo en el marco de los proyectos PID2023-146797OB-C31, PID2023-146797OB-C32, PID2019-107601RB-C31 y PID2019-107601RA-C32 financiados por MCIN/AEI/10.1303910.13039/501100011033 y por el FEDER, UE. El trabajo de P.M.M., S.A.B. y M.J.d.M. (CITA) también contó con el apoyo del Gobierno de Aragón (Grupo de Investigación A21_23R). N.L. fue beneficiario de la beca de doctorado financiada por PRE2020-093859.
dc.identifier.citationLopez, N., Andrés-Barranco, S., De Miguel, M. J., Zúñiga-Ripa, A., Elizalde-Bielsa, A., Salvador-Bescós, M., Iriarte, M., Barberán, M., Blasco, J. M., Moriyón, I., Conde-Álvarez, R., & Muñoz, P. M. (2026). Conjunctival administration of H38ΔwbkF rough vaccine as an effective strategy to protect against Brucella ovis infection while minimizing serological interference. Veterinary Research. https://doi.org/10.1186/s13567-025-01693-8
dc.identifier.doi10.1186/s13567-025-01693-8
dc.identifier.issn1297-9716
dc.identifier.urihttps://doi.org/10.1186/s13567-025-01693-8
dc.identifier.urihttps://hdl.handle.net/10532/8180
dc.language.isoen
dc.publisherSpringer Nature Limited
dc.relationinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2023-146797OB-C32/ES/AVANZANDO EN VACUNAS SEGURAS CONTRA LA BRUCELOSIS OVINA: EFICACIA DE CANDIDATOS VACUNALES MEJORADOS DE B. MELITENSIS Y B. OVIS Y MODELOS IN VITRO INNOVADORES/BruVac-Cell
dc.relationinfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-107601RB-C31/ES/Brucellosis ovina: vacunas seguras y estrategias DIVA frente a B. melitensis y B. ovis/Bru-DIsafe
dc.relation.citaSi
dc.relation.publisherversionhttps://doi.org/10.1186/s13567-025-01693-8
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.agrovocBrucella melitensis
dc.subject.agrovocBrucella ovis
dc.subject.agrovocBrucelosis
dc.subject.agrovocOvino
dc.subject.agrovocFisiología animal
dc.subject.sdgSalud y bienestar
dc.subject.sdgHambre cero
dc.titleConjunctival administration of H38ΔwbkF rough vaccine as an effective strategy to protect against Brucella ovis infection while minimizing serological interference
dc.typeartículo original
dc.type.hasVersionversión sometida a revisión

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