<i>Brucella abortus</i>
            Strain RB51 Leucine Auxotroph as an Environmentally Safe Vaccine for Plasmid Maintenance and Antigen Overexpression

Rajasekaran, P.; Seleem, Mohamed N.; Contreras, Andrea; Purwantini, Endang; Schurig, Gerhardt G.; Sriranganathan, Nammalwar; Boyle, Stephen M.

doi:10.1128/aem.01511-08

Cited by 14 publications

(18 citation statements)

References 15 publications

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“…RB51 has been used to overexpress Cu/Zn superoxide dismutase (SOD) [31] and express Brucella glycosyl-transferase ( WboA ) [33] to achieved enhanced vaccine efficacy. RB51 leuB is an unmarked leuB mutant of RB51 [34]. The leuB gene, encoding isopropyl malate dehydrogenase, is essential for the biosynthesis of leucine in B. abortus .…”

Section: Resultsmentioning

confidence: 99%

Meta-analysis of variables affecting mouse protection efficacy of whole organism Brucella vaccines and vaccine candidates

et al. 2013

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BackgroundVaccine protection investigation includes three processes: vaccination, pathogen challenge, and vaccine protection efficacy assessment. Many variables can affect the results of vaccine protection. Brucella, a genus of facultative intracellular bacteria, is the etiologic agent of brucellosis in humans and multiple animal species. Extensive research has been conducted in developing effective live attenuated Brucella vaccines. We hypothesized that some variables play a more important role than others in determining vaccine protective efficacy. Using Brucella vaccines and vaccine candidates as study models, this hypothesis was tested by meta-analysis of Brucella vaccine studies reported in the literature.ResultsNineteen variables related to vaccine-induced protection of mice against infection with virulent brucellae were selected based on modeling investigation of the vaccine protection processes. The variable "vaccine protection efficacy" was set as a dependent variable while the other eighteen were set as independent variables. Discrete or continuous values were collected from papers for each variable of each data set. In total, 401 experimental groups were manually annotated from 74 peer-reviewed publications containing mouse protection data for live attenuated Brucella vaccines or vaccine candidates. Our ANOVA analysis indicated that nine variables contributed significantly (P-value < 0.05) to Brucella vaccine protection efficacy: vaccine strain, vaccination host (mouse) strain, vaccination dose, vaccination route, challenge pathogen strain, challenge route, challenge-killing interval, colony forming units (CFUs) in mouse spleen, and CFU reduction compared to control group. The other 10 variables (e.g., mouse age, vaccination-challenge interval, and challenge dose) were not found to be statistically significant (P-value > 0.05). The protection level of RB51 was sacrificed when the values of several variables (e.g., vaccination route, vaccine viability, and challenge pathogen strain) change. It is suggestive that it is difficult to protect against aerosol challenge. Somewhat counter-intuitively, our results indicate that intraperitoneal and subcutaneous vaccinations are much more effective to protect against aerosol Brucella challenge than intranasal vaccination.ConclusionsLiterature meta-analysis identified variables that significantly contribute to Brucella vaccine protection efficacy. The results obtained provide critical information for rational vaccine study design. Literature meta-analysis is generic and can be applied to analyze variables critical for vaccine protection against other infectious diseases.

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Section: Resultsmentioning

confidence: 99%

Meta-analysis of variables affecting mouse protection efficacy of whole organism Brucella vaccines and vaccine candidates

et al. 2013

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“…An unmarked mutation was created in the entF gene of strain B. abortus 2308 using the cre‐lox methodology as described previously (Rajasekaran et al , 2008). A segment containing 497 base pairs were deleted within the entF gene without incorporating any antibiotic‐resistant marker in the mutant.…”

Section: Methodsmentioning

confidence: 99%

Effect of entF deletion on iron acquisition and erythritol metabolism by Brucella abortus 2308

Jain¹,

Rodríguez²,

Kimsawatde³

et al. 2011

FEMS Microbiology Letters

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Brucella abortus has been shown to produce two siderophores: 2,3-dihydroxybenzoic acid (2,3-DHBA) and brucebactin. Previous studies on Brucella have shown that 2,3-DHBA is associated with erythritol utilization and virulence in pregnant ruminants. The biosynthetic pathway and role of brucebactin are not known and the only gene shown to be involved so far is entF. Using cre-lox methodology, an entF mutant was created in wild-type B. abortus 2308. Compared with the wild-type strain, the ΔentF strain showed significant growth inhibition in iron minimal media that became exacerbated in the presence of an iron chelator. For the first time, we have demonstrated the death of the ΔentF strain under iron-limiting conditions in the presence of erythritol. Addition of FeCl(3) restored the growth of the ΔentF strain, suggesting a significant role in iron acquisition. Further, complementation of the ΔentF strain using a plasmid containing an entF gene suggested the absence of any polar effects. In contrast, there was no significant difference in survival and growth between the ΔentF and wild-type strains grown in the murine macrophage cell line J774A.1, suggesting that an alternate iron acquisition pathway is present in Brucella when grown intracellulary.

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“…The antibiotic marker is used in the screening of transformed clones, but it is not desirable in the final vaccine due to the potential of spreading antibiotic resistance genes. Options, as an RB51 leucine auxotroph, have been explored to avoid this issue [ 92 ]. Additionally, so far, there is no data available to exclude the possibility that these live mutants will not have similar safety and diagnostic issues as live strains, especially if made from smooth strains.…”

Section: Vaccination With Recombinant Genes Proteins Vectors Andmentioning

confidence: 99%

Recent advances in Brucella abortus vaccines

Dorneles

Sriranganathan

Lage

2015

Vet Res

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149

116

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Brucella abortus vaccines play a central role in bovine brucellosis control/eradication programs and have been successfully used worldwide for decades. Strain 19 and RB51 are the approved B. abortus vaccines strains most commonly used to protect cattle against infection and abortion. However, due to some drawbacks shown by these vaccines much effort has been undertaken for the development of new vaccines, safer and more effective, that could also be used in other susceptible species of animals. In this paper, we present a review of the main aspects of the vaccines that have been used in the brucellosis control over the years and the current research advances in the development of new B. abortus vaccines.

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Brucella abortus Strain RB51 Leucine Auxotroph as an Environmentally Safe Vaccine for Plasmid Maintenance and Antigen Overexpression

Cited by 14 publications

References 15 publications

Meta-analysis of variables affecting mouse protection efficacy of whole organism Brucella vaccines and vaccine candidates

Meta-analysis of variables affecting mouse protection efficacy of whole organism Brucella vaccines and vaccine candidates

Effect of entF deletion on iron acquisition and erythritol metabolism by Brucella abortus 2308

Recent advances in Brucella abortus vaccines

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