Evaluation of novel Brucella melitensis unmarked deletion mutants for safety and efficacy in the goat model of brucellosis
ABSTRACT Pregnant goats were employed to assess unmarked deletion mutant vaccine candidates BMDeltaasp24, BMDeltacydBA, and BMDeltavirB2, as the target host species naturally infected with Brucella melitensis. Goats were assessed for the degree of pathology associated with the vaccine strains as well as the protective immunity afforded by each strain against abortion and infection after challenge with wild-type Brucella melitensis 16M. Both BMDeltaasp24 and BMDeltavirB2 were considered safe vaccine candidates in the pregnant goat model because they did not cause abortion or colonize fetal tissues. BMDeltaasp24 was isolated from the maternal tissues only, indicating a slower rate of clearance of the vaccine strain than for BMDeltavirB2, which was not isolated from any maternal or fetal tissues. Both strains were protective against abortion and against infection in the majority of pregnant goats, although BMDeltaasp24 was more efficacious than BMDeltavirB2 against challenge infection.
- SourceAvailable from: onlinelibrary.wiley.com
[Show abstract] [Hide abstract]
- "The T4SS is required for persistence in both the mouse, and in a natural host, the goat (Hong et al., 2000; Sieira et al., 2000; Kahl-McDonagh et al., 2006; Zygmunt et al., 2006). After both intraperitoneal (i.p.) and intragastric (i.g.) inoculation of mice, virB mutants are able to disseminate to systemic sites such as lymph nodes, liver and spleen, suggesting that while the T4SS may contribute to this step, it is not critical (Rolan and Tsolis, 2007; Paixao et al., 2009). "
ABSTRACT: In humans, pathogenic Brucella species cause a febrile illness known as brucellosis. A key pathogenic trait of this group of organisms is their ability to survive in immune cells and persist in tissues of the reticuloendothelial system, a process that requires the function of a Type IV secretion system. In contrast to other well-studied Gram-negative bacteria, Brucella spp. do not cause inflammation at the site of invasion, but have a latency period of 2-4 weeks before the onset of symptoms. This review discusses several mechanisms that allow Brucella spp. both to evade detection by pattern recognition receptors of the innate immune system and suppress their signalling. In contrast to these stealth features, the VirB Type IV secretion system, which mediates survival within phagocytic cells, stimulates innate immune responses in vivo. The responses stimulated by this virulence factor are sufficient to check bacterial growth, but not to elicit sterilizing immunity. The result is a stand-off between host and pathogen that results in persistent infection.Cellular Microbiology 09/2010; 12(9):1195-202. DOI:10.1111/j.1462-5822.2010.01498.x · 4.82 Impact Factor