Evaluation in mice of Brucella ovis attenuated mutants for use as live vaccines against B. ovis infection

Sancho, Pilar; Tejedor, Carmen; Sidhu-Muñoz, Rebeca S; Fernández-Lago, Luis; Vizcaı́no, Nieves

doi:10.1186/1297-9716-45-61

Cited by 28 publications

(27 citation statements)

References 44 publications

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“…In flocks with a high incidence of the disease, this strategy could be financially unsustainable. There are good indications in the development of a new vaccine against B. ovis that has thus far been tested on mice (38). However, to date, only the vaccine B. melitensis Rev 1 has proven to be effective in the control of infections with the species B. ovis (1,7).…”

Section: Discussionmentioning

confidence: 99%

Infectious epididymitis caused by Brucella ovis in Croatian sheep flocks

Cvetnić¹,

Zdelar-Tuk²,

Duvnjak³

et al. 2017

Turk J Vet Anim Sci

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Špičić et al. (8) first described infectious epididymitis in rams in Croatia. The disease was later proven to be present in most counties in the country (9). Infection with the species B. ovis has been confirmed in virtually all countries with prominent sheep production. It has been reported in the neighboring countries of Slovenia (10) and Serbia (5,11). It has also been confirmed in Romania (12), Austria (13), Italy (14), Switzerland (15), Spain (3), Russia (16), Ukraine (17), Australia (2,18), New Zealand (19,20), Canada (4,21), and the United States (22).The objective of this study was to determine the prevalence of ovine epididymitis in different regions of Croatia. Serological testing was conducted over a 5-year period (2011 to 2015) annually in rams and in sheep after abortion, and material from rams and aborted fetuses was used to isolate and identify the causative agent using bacteriological and molecular methods.

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Section: Discussionmentioning

confidence: 99%

Infectious epididymitis caused by Brucella ovis in Croatian sheep flocks

Cvetnić¹,

Zdelar-Tuk²,

Duvnjak³

et al. 2017

Turk J Vet Anim Sci

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“…In areas with a high prevalence , this strategy might be economically unsustainable. Despite recently developed B. ovis mutant attenuated strains gave promising protecting results in mice [ 17 , 18 ], the B. melitensis Rev.1 vaccine remains up to now the only vaccine with proven efficacy against B. ovis infection in rams [ 2 ]; therefore, Rev.1 vaccination would be certainly the most economical and practicable tool for midterm control in such situations [ 3 ], in particular in areas where export of rams or ram semen is not an economical priority and where the official brucellosis-free status is not a short-term goal.…”

Section: Discussionmentioning

confidence: 99%

Contagious epididymitis due to Brucella ovis: relationship between sexual function, serology and bacterial shedding in semen

Picard‐Hagen

Berthelot

Champion³

et al. 2015

BMC Vet Res

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BackgroundContagious Epididymitis (CE) due to Brucella ovis (B. ovis) is a contagious disease that impairs rams’ fertility due to epididymis, testicle and accessory sexual gland alterations. An increased incidence of CE has been observed in South Eastern France (“PACA” region) since the Rev.1 vaccination against B. melitensis has been stopped in 2008. The objective of this study was to evaluate the relationship between the infection by B. ovis and the sexual function of rams.Two-hundred eighteen sexually-mature rams, from 11 seropositive flocks, were submitted to a clinical examination of the genital tract, a semen collection by electro-ejaculation for spermogram and culture, and a serological examination for anti-B. ovis antibodies by complement fixation test (CFT) and indirect ELISA (I-ELISA). The relationships between clinical, seminal, bacteriological and serological parameters were studied using the Fisher exact test and a logistic regression model (binomial logit).ResultsB. ovis shedding in semen was significantly associated with seropositivity (CFT and I-ELISA; p < 0.001 and 0.01 respectively), genital tract alterations (p < 0.05) and poor semen quality (p < 0.001). Seropositive rams presented significantly more genital tract alterations (p < 0.001) and a poor seminal score (p < 0.001) than seronegative rams.ConclusionsSince semen culture is not routinely feasible in field conditions, a control plan of CE should be based, where Rev.1 vaccination is not possible, on both systematic clinical and serological examination of rams, followed by the culling of seropositive and/or genital tract alterations carrier rams.

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“…abortus 2308 ( Briones et al, 2001 ). The Δ cgs mutant of B. ovis PA was also highly attenuated when it was intraperitoneally inoculated at a dose of 10 6 colony forming units (CFU)/mouse ( Martín-Martín et al, 2012 ), but when the dose usually employed for protection experiments (10 8 CFU/mouse) ( Sancho et al, 2014 ; Soler-Lloréns et al, 2014 ; Silva et al, 2015b ) was used, the bacterial counts in spleen increased to levels that were close to those of the parental strain (unpublished results). Several combinations of deleted genes were tempted in the panel of multiple mutants, although, keeping in mind the development of an attenuated vaccine, the inclusion of Δ cgs and Δ omp31 mutations was prioritized for two reasons: (i) to study how the addition of new mutations could increase the attenuation of the Δ cgs single mutant to appropriate levels for an attenuated vaccine, and (ii) Omp31 is an abundant OMP in the OM of B. ovis PA ( Martín-Martín et al, 2009 ), it is the most immunogenic OMP in the course of B. ovis infection ( Kittelberger et al, 1998 ) and its interest for a serological diagnosis favoring the differentiation between infected and vaccinated animals (DIVA diagnosis) has also been evidenced ( Vizcaíno et al, 2001b ).…”

Section: Introductionmentioning

confidence: 96%

Characterization of Cell Envelope Multiple Mutants of Brucella ovis and Assessment in Mice of Their Vaccine Potential

et al. 2018

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Brucella ovis is a non-zoonotic Brucella species lacking specific vaccine. It presents a narrow host range, a unique biology relative to other Brucella species, and important distinct surface properties. To increase our knowledge on its peculiar surface and virulence features, and seeking to develop a specific vaccine, multiple mutants for nine relevant cell-envelope-related genes were investigated. Mutants lacking Omp10 plus Omp19 could not be obtained, suggesting that at least one of these lipoproteins is required for viability. A similar result was obtained for the double deletion of omp31 and omp25 that encode two major surface proteins. Conversely, the absence of major Omp25c (proved essential for internalization in HeLa cells) together with Omp25 or Omp31 was tolerated by the bacterium. Although showing important in vitro and in vivo defects, the Δomp10Δomp31Δomp25c mutant was obtained, demonstrating that B. ovis PA survives to the simultaneous absence of Omp10 and four out seven proteins of the Omp25/Omp31 family (i.e., Omp31, Omp25c, Omp25b, and Omp31b, the two latter naturally absent in B. ovis). Three multiple mutants were selected for a detailed analysis of virulence in the mouse model. The Δomp31Δcgs and Δomp10Δomp31Δomp25c mutants were highly attenuated when inoculated at 106 colony forming units/mouse but they established a persistent infection when the infection dose was increased 100-fold. The Δomp10ΔugpBΔomp31 mutant showed a similar behavior until week 3 post-infection but was then totally cleared from spleen. Accordingly, it was retained as vaccine candidate for mice protection assays. When compared to classical B. melitensis Rev1 heterologous vaccine, the triple mutant induced limited splenomegaly, a significantly higher antibody response against whole B. ovis PA cells, an equivalent memory cellular response and, according to spleen colonization measurements, better protection against a challenge with virulent B. ovis PA. Therefore, it would be a good candidate to be evaluated in the natural host as a specific vaccine against B. ovis that would avoid the drawbacks of B. melitensis Rev1. In addition, the lack in this attenuated strain of Omp31, recognized as a highly immunogenic protein during B. ovis infection, would favor the differentiation between infected and vaccinated animals using Omp31 as diagnostic target.

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Evaluation in mice of Brucella ovis attenuated mutants for use as live vaccines against B. ovis infection

Cited by 28 publications

References 44 publications

Infectious epididymitis caused by Brucella ovis in Croatian sheep flocks

Infectious epididymitis caused by Brucella ovis in Croatian sheep flocks

Contagious epididymitis due to Brucella ovis: relationship between sexual function, serology and bacterial shedding in semen

Characterization of Cell Envelope Multiple Mutants of Brucella ovis and Assessment in Mice of Their Vaccine Potential

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