Abstract
The rise in antibiotic resistant strains of bacteria has led to the need for new methods of combatting bacterial infection. Since the surfaces of bacteria are covered in uniquely patterned capsular polysaccharides, vaccines targeting these polysaccharides have become a popular field of research for protection against pathogenic bacteria. Though licensed polysaccharide vaccines are commercially available, they lack the efficiency to protect patients that are immunocompromised or at high risk because they elicit T cell independent immune responses, resulting in low-affinity antibodies. To elicit a T cell dependent response and thereby recruit B cells that produce high-affinity antibodies, a vaccine was developed consisting of a short target oligosaccharide antigen of no more than four carbohydrate units, a virus-like particle that the antigen is conjugated to, and an NKT cell adjuvant that recruits T cell help. Previously the vaccine utilized in this work successfully elicited the T cell dependent adaptive immune response desired, and B cells were isolated producing high-affinity antibodies to our specific targets. The previous results were from using tetrasaccharide antigens for serotypes 14 and 3 of Streptococcus pneumonia (Sp). To further optimize this vaccine, disaccharides were tested as minimal epitopes for high-affinity antibody production to specific serotypes of Sp. Four disaccharides were synthesized for serotypes 3, 4, 7F, and 9v, one for each serotype. The synthesis of each disaccharide is described. These disaccharides were tested using the vaccine platform we developed. Reactive B cells were isolated producing high-affinity antibodies to the serotype 3 disaccharide antigen. For the other disaccharides only weak antibody responses were observed.
Degree
PhD
College and Department
Physical and Mathematical Sciences; Chemistry and Biochemistry
Rights
https://lib.byu.edu/about/copyright/
BYU ScholarsArchive Citation
Taylor, Seth A., "Design, Synthesis and Immunological Testing of Minimal Oligosaccharide Epitopes for Glycoconjugate Vaccines Targeting Capsular Polysaccharides of Serotypes 3, 4, 7F and 9V of Streptococcus Pneumoniae" (2023). Theses and Dissertations. 10031.
https://scholarsarchive.byu.edu/etd/10031
Date Submitted
2023-06-22
Document Type
Dissertation
Handle
http://hdl.lib.byu.edu/1877/etd12869
Keywords
conjugate vaccines, synthesis, glycan antibodies, glycan antigens, serotype, Streptococcus pneumonia
Language
english