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Conjunctival administration of H38ΔwbkF rough vaccine as an effective strategy to protect against Brucella ovis
Nerea Lopez1, Sara Andrés-Barranco2,3, M Jesús De Miguel2,3
1Department of Microbiology and Parasitology, Instituto de Investigación Sanitaria de Navarra (IdiSNA), University of Navarra, 31008, Pamplona, Spain.
Abstract:
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.
Insights
Developing a new vaccine for sheep brucellosis is crucial. A modified B. melitensis vaccine (H38ΔwbkF) administered conjunctivally shows promise for eradicating B. ovis without interfering with disease surveillance tests.
Area of Science:
- Veterinary immunology
- Bacteriology
- Vaccinology
Background:
- Sheep brucellosis, caused by Brucella melitensis and B. ovis, results in significant economic losses.
- B. melitensis is zoonotic, while B. ovis is not, necessitating distinct control strategies.
- Current vaccines like B. melitensis Rev1 interfere with diagnostic tests for B. melitensis surveillance.
Purpose of the Study:
- To develop an effective vaccine against B. ovis that does not interfere with B. melitensis surveillance.
- To explore strategies for minimizing serological interference from a B. ovis vaccine candidate.
Main Methods:
- Construction of B. melitensis R mutant H38ΔwbkF core-defective mutants (wadB, wadC).
- Subcutaneous and conjunctival administration of H38ΔwbkF vaccine in rams.
- Evaluation of vaccine efficacy in mice and rams, and assessment of serological interference with diagnostic tests.
Main Results:
- Core-defective mutants were over-attenuated and failed to protect mice.
- Conjunctival administration of H38ΔwbkF preserved vaccine efficacy in rams.
- Conjunctival vaccination significantly reduced serological interference with diagnostic tests.
Conclusions:
- Conjunctival administration of H38ΔwbkF is a viable strategy for B. ovis eradication in B. melitensis-free areas.
- This approach minimizes interference with essential B. melitensis surveillance tests.
