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

Watkins, Hannah Christine

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

Abstract

Subunit 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.

Date Issued

2017-01-30

Keywords

E. coli; Immunology; Biomedical engineering; vaccine; Influenza; Lipopolysaccharide; M2e; Outer membrane vesicle; Virology

Committee Chair

Putnam, David A.

Committee Member

Delisa, Matthew
Whittaker, Gary R

Degree Discipline

Biomedical Engineering

Degree Name

Ph. D., Biomedical Engineering

Degree Level

Doctor of Philosophy

Types

dissertation or thesis