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Recombinant Escherichia coli derived outer membrane vesicles for safe and effective subunit antigen delivery

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dc.contributor.authorWatkins, Hannah Christine
dc.contributor.chairPutnam, David A.
dc.contributor.committeeMemberDelisa, Matthew
dc.contributor.committeeMemberWhittaker, Gary R
dc.date.accessioned2017-04-04T20:28:03Z
dc.date.available2019-02-01T07:05:10Z
dc.date.issued2017-01-30
dc.description.abstractSubunit vaccines rely on adjuvants to drive an immune response against antigens of interest. Improved adjuvant platforms, capable of interaction with specific pathogen recognition receptors in the innate immune system, can lead to more effective and longer lasting vaccines. Recombinant outer membrane vesicles (rOMVs) are a recently developed adjuvant system that harnesses the natural pathogen associated molecular patterns present in the outer membrane of E. coli to direct an immune response against recombinant antigens displayed on the rOMV surface. Though rOMV vaccines have demonstrated promise against viral antigens in murine models, their high lipopolysaccharide (LPS) content hinders translation to humans. This dissertation will present ways in which the LPS in rOMVs can be modified, through use of ‘detoxified’ commercial E. coli strains, as well as through genetic manipulation of probiotic E. coli strains, to generate rOMVs with greatly improved safety profiles. Additionally, it will profile the development of a potential pandemic influenza vaccine using detoxified rOMVs, demonstrating their feasibility in achieving protective immune responses.
dc.identifier.doihttps://doi.org/10.7298/X46H4FF1
dc.identifier.otherWatkins_cornellgrad_0058F_10101
dc.identifier.otherhttp://dissertations.umi.com/cornellgrad:10101
dc.identifier.otherbibid: 9906090
dc.identifier.urihttps://hdl.handle.net/1813/47843
dc.language.isoen_US
dc.subjectE. coli
dc.subjectImmunology
dc.subjectBiomedical engineering
dc.subjectvaccine
dc.subjectInfluenza
dc.subjectLipopolysaccharide
dc.subjectM2e
dc.subjectOuter membrane vesicle
dc.subjectVirology
dc.titleRecombinant Escherichia coli derived outer membrane vesicles for safe and effective subunit antigen delivery
dc.typedissertation or thesis
dcterms.licensehttps://hdl.handle.net/1813/59810
thesis.degree.disciplineBiomedical Engineering
thesis.degree.grantorCornell University
thesis.degree.levelDoctor of Philosophy
thesis.degree.namePh. D., Biomedical Engineering

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