Conjunctival administration of H38ΔwbkF rough vaccine as an effective strategy to protect against Brucella ovis infection while minimizing serological interference
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Date
2026-03-08
Authors
López Fernández, NereaAndrés Barranco, Sara
Miguel López, María Jesús de
Zúñiga Ripa, Amaia
Elizalde Bielsa, Aitor
Salvador Bescós, Miriam
Iriarte, Maite
Barberán Pelegrín, Montserrat
Blasco Martínez, José María
Moriyón Uria, Ignacio
Conde Álvarez, Raquel
Muñoz Álvaro, Pilar María
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Springer Nature Limited
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artículo originalAbstract
Sheep 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.
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Bibliographic citation
Lopez, 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
AGROVOC subjects
Brucella melitensisBrucella ovis
Brucelosis
Ovino
Fisiología animal
Sponsorship
Esta 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.