**6. Preclinical evaluation of therapeutic interventions and vaccines**

Pharmacotherapy is the main therapeutic intervention for the treatment of human Brucellosis, including Brucellar spondylodiscitis. Ciprofloxacin, doxycycline, rifampin has been utilized for the evaluation of the efficiency of different pharmacotherapies for human Brucellosis [37–39]. Different combination of rifampicin, doxycycline, and spiramycin or moxifloxacin were analyzed in rat Brucellosis model for the potential therapeutic options [40, 42]. Oxytetracycline combined with streptomycin were evaluated in the sheep for the test of practical and cost-effective treatment regimen for Brucellosis [59]. Additionally, as a new antibiotic carrier, the microspheres have been used to test for a treatment effect of *Brucella* infection [62]. Microspheres based on poly (lactide-co-glycolide) wherein gentamicin entrapped have been tested to target gentamicin to the cells of the monocyte–macrophage system to reduce drug toxicity and control its release over several days [63]. However, Prior and colleagues reported that mice infected with virulent strains of *Brucella* and treated with three intraperitoneal doses of 100 μg gentamicin microspheres were not able to reduce bacterial load in the spleen after 1 and 3 weeks posttreatment [37].

Surgery should be performed to treat Brucellar spondylodiscitis if the pharmacotherapy is poorly done. The indications for surgery included the following: persistent pain due to spinal instability, severe or progressive neurologic dysfunction due to nerve root compression by inflammatory granuloma or epidural abscesses, and no response to antibiotic therapy [9, 64]. The preclinical model is critical for the research of the improvement of surgery protocols. However, the rabbit model was originally developed for the study of Brucellar spondylodiscitis. Future studies are needed to further refine the surgical procedures.

By far, the quality of live vaccines that are commercially used for preventing animal Brucellosis is evaluated in mouse models. Live *Brucella abortus* (strain S19), which is the most widely used vaccine in cattle, has been tested in mice. The mice were previously treated with 105 CFU of Brucella reference strain S19 vaccine [15]. All mice were injected intraperitoneally with 105 CFU of *Brucella* 30 days after the vaccination. The commercial vaccine is considered efficient when mice have a significantly lower bacterial load than the unvaccinated control group and when the vaccinated group has similar immunogenicity value to the mice group vaccinated with S19 reference strain [15]. Recently, a new candidate vector vaccine against human Brucellosis based on recombinant influenza viral vectors subtypes H5N1 expressing *Brucella* outer membrane protein (Omp) 16, L7/L12, Omp19 or copper/ zinc superoxide dismutase proteins has been developed [65]. The effectiveness of

*Preclinical Models of Brucellar Spondylodiscitis DOI: http://dx.doi.org/10.5772/intechopen.98754*

the new anti-Brucellosis vector vaccine was determined by studying its protective effect after conjunctival, intranasal and sublingual administration in doses 105 50% egg infective dose (EID50), 106 EID50 and 107 EID50 during prime and boost vaccinations of animals, followed by challenge with virulent strains of *Brucella* infection. Double intranasal immunization of guinea pigs at a dose of 106 EID50, which provided 80% protection of guinea pigs from *Brucella* infection [65]. The proposed vaccine has achieved the best level of protection, which in turn provides a basis for its further promotion.
