Abstract

There is a rise in prevalence of antibiotic resistance in Streptococcus pneumoniae, and its FDA-approved vaccines often do not mount effective immune responses in children, the elderly, or the immunocompromised. One reason these vaccines are generally less effective is because they do not utilize T-cell help. T-cell help can be accessed when di-, tri-, or tetra-saccharides positioned inside major histocompatibility complex (MHC) II are presented to T-cell receptors as a target antigen. Pairing MHC II-antigen complexes with T-cell receptors enables development of B and T lymphocytes that are highly specific to these antigens, granting an increase in antibody affinity and cell memory. One problem with today's vaccines against S. pneumoniae, in contrast, is that extracted, polymeric sugars cannot be presented to T-cells by MHC because they do not fit inside the MHC II complex due to their large molecular size. Thus, FDA-approved vaccines generate antibodies which have inadequate affinities and are largely nonspecific in their targets. This thesis covers the synthesis of a functionalized S. pneumoniae serotype 6A disaccharide and trisaccharide, which are core components of the repeating unit of natural capsular polysaccharides, and can be used to obtain necessary T-cell help in working vaccines and good monoclonal antibodies.

Degree

MS

College and Department

Physical and Mathematical Sciences

Rights

https://lib.byu.edu/about/copyright/

Date Submitted

2020-05-26

Document Type

Thesis

Handle

http://hdl.lib.byu.edu/1877/etd11638

Keywords

Streptococcus pneumoniae, serotype 6a, synthesis, glycan, antibodies, vaccine, immunotherapy

Language

english

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