Degree

Doctor of Philosophy (PhD)

Department

Chemistry

Document Type

Dissertation

Abstract

Glycoconjugate vaccines have become an effective strategy for protection against an array of globally persistent diseases resulting from pathogenic bacteria such as Haemophilus influenzae type b (Hib), Neisseria meningitidis, and Salmonella enterica serotype Typhi. Comprised of a carbohydrate (referred to as glycan) covalently inked to a carrier protein, these vaccines can initiate adaptive immunity by inducing B and T cell responses once in the lymphatic system. This is particularly relevant for infants two years of age and younger whose immune systems are not fully developed. A continuously emerging threat in clinical settings, Acinetobacter baumannii is a Gram-negative bacterium that exhibits ever-increasing levels of antibiotic resistance. Currently, no FDA-approved vaccines against A. baumannii exist, but a glycoconjugate vaccine against this pathogen could provide a preventative measure with the potential to establish long-term adaptive immunity. To accomplish this, a well-conserved glycan epitope is required, and a lipooligosaccharide (LOS) from A. baumannii strain ATCC19606 was identified which is believed to exist in nearly 74% of strains of A. baumannii including most clinical isolates. Considering the difficulty and hazards associated with large-scale fermentation of A. baumannii and isolation of this LOS, chemical synthesis using O-glycosylation represents the most viable option for acquiring this glycan. The aim of this work is the synthesis of a suitable carbohydrate hapten for a glycoconjugate vaccine against A. baumannii. The synthesis of multiple portions of a LOS from A. baumannii strain ATCC19606 is reported. These subunits will allow for investigation of structure-activity relationships and increase the potential for identifying a widely conserved glycan epitope through immunological experimentation.

Date

7-25-2024

Committee Chair

Ragains, Justin R.

Download

Share

COinS