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dc.contributor.authorWalker, Michelle Kayen_US
dc.date.accessioned2015-07-18T06:00:20Z
dc.date.available2015-07-18T06:00:20Z
dc.date.issued2014-01-23en_US
dc.identifier.othervt_gsexam:1814en_US
dc.identifier.urihttp://hdl.handle.net/10919/54564
dc.description.abstractBrucella abortus is amongst the top 5 zoonotic diseases worldwide. The overall goal of this research is to generate a safe and effective vaccine for humans. Brucella abortus strain RB51, approved for use in cattle, provides protection by initiating a strong T-helper 1 (Th1) type response is a candidate vaccine. Based on a model for aerosol exposure mice were vaccinated intranasally (IN) with strain RB51 and challenged IN with B. abortus strain 2308, strain RB51 did not protect. Protection against Brucella is mediated through TLRs 2, 4 and 9. The addition of TLR 2 or TLR 4 and a trend with TLR9 agonists with intranasal RB51 vaccination significantly increased bacterial clearance in the lung after strain 2308 challenge. Therefore, we hypothesized that combining TLR agonists 2, 4, and 9 with strain RB51 IN would upregulate protection and clearance in the lung against strain 2308 challenge (IN), by upregulating the DC1 and CD4 Th1 and CD8 immune response. This study showed that protection is not upregulated by combining all TLR agonists. Overall the addition of TLR 2 and 4 vs. TLR 2, 4 and 9 agonists affects the immune response and impacts the level of clearance. Our data support the development of a DC1 Th1 CD8 response, based on serology, and both DC and T-cell activation and function by the group which received the TLR 2 and 4 agonists and to a lesser degree the group receiving TLR 2, 4, and 9 agonists. Additional studies are warranted to further define the differential mechanisms and endpoints of protection.en_US
dc.format.mediumETDen_US
dc.publisherVirginia Techen_US
dc.rightsThis Item is protected by copyright and/or related rights. Some uses of this Item may be deemed fair and permitted by law even without permission from the rights holder(s), or the rights holder(s) may have licensed the work for use under certain conditions. For other uses you need to obtain permission from the rights holder(s).en_US
dc.subjectBrucella abortusen_US
dc.subjectinnate immunityen_US
dc.subjectdendritic cellsen_US
dc.subjectvaccine strains RB51en_US
dc.subjecttoll-like receptorsen_US
dc.subjectintranasal vaccinationen_US
dc.titleThe ability of TLR agonists to upregulate Brucella abortus strain RB51 mediated protection in a murine respiratory modelen_US
dc.typeThesisen_US
dc.contributor.departmentVeterinary Medicineen_US
dc.description.degreeMaster of Scienceen_US
thesis.degree.nameMaster of Scienceen_US
thesis.degree.levelmastersen_US
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen_US
thesis.degree.disciplineBiomedical and Veterinary Sciencesen_US
dc.contributor.committeechairWitonsky, Sharon G.en_US
dc.contributor.committeememberZimmerman, Kurt L.en_US
dc.contributor.committeememberSriranganathan, Nammalwaren_US
dc.contributor.committeememberKanevsky, Isisen_US


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