Determination of optimal prime-boost vaccination regimens against zaire ebolavirus

dc.contributor.authorAviles, Jenna
dc.contributor.examiningcommitteeStrong, Jim (Medical Microbiology) Babiuk, Shawn (Immunology)en_US
dc.contributor.supervisorKobinger, Gary (Medical Microbiology)en_US
dc.date.accessioned2013-08-29T14:51:30Z
dc.date.available2013-08-29T14:51:30Z
dc.date.issued2013-08-29
dc.degree.disciplineImmunologyen_US
dc.degree.levelMaster of Science (M.Sc.)en_US
dc.description.abstractZaire ebolavirus is a long filamentous single-stranded RNA virus belonging to the family Filoviridae. Due to the virus’ high mortality rate, lack of an approved vaccine, and potential use as a bioterrorism weapon, research on this topic has been of high demand. To address this issue, several vector platforms have been investigated as vaccine candidates. DNA and adenovirus vaccine platforms are known to elicit robust cellmediated immune responses, while adeno-associated virus and vesicular stomatitis virus vaccines are recognized for strong humoral responses. The leading hypothesis of the present project was to determine whether these four vaccination platforms, in a heterologous prime-boost regimen, increase survival and the breadth of the immune response. To test this hypothesis, the main objectives were to evaluate the cell-mediated and humoral immune responses, as well as correlate the induced immunity to protection against MA-EBOV. The heterologous pairings were strategically designed to induce both arms of the immune response. An optimized Zaire ebolavirus glycoprotein was inserted into each of the vaccine platforms and evaluated against mouse-adapted Zaire ebolavirus. Serum obtained from vaccinated mice was analyzed by a neutralizing antibody assay and IgG ELISA to determine the humoral response. The cell-mediated immune response was monitored via ELISPOT. Collectively, the data indicates that regardless of whether homologous or heterologous, a more robust immune response was observed in prime-boost strategies compared to an individual vaccination alone. In addition, the cell-mediated and humoral data show that heterologous combinations induce higher IgG specific titers in comparison to homologous regimens. As expected and consequent with immune responses, survival studies demonstrate that prime-boost III vaccinations, heterologous or homologous, are superior to vaccination regimens involving only one strategy. This data supports further evaluation of the prime-boost strategies to develop an optimal immunization strategy that can be applied to other disease models.en_US
dc.description.noteOctober 2013en_US
dc.identifier.urihttp://hdl.handle.net/1993/22128
dc.language.isoengen_US
dc.rightsopen accessen_US
dc.subjectVaccineen_US
dc.subjectEbolaen_US
dc.titleDetermination of optimal prime-boost vaccination regimens against zaire ebolavirusen_US
dc.typemaster thesisen_US
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