Abstract

Streptococcus pneumoniae (Spn) is a globally prevalent Gram-positive pathogen responsible for invasive pneumococcal diseases (IPD). Among its over 90 serotypes, Spn serotypes 6A (Sp6A) and 6B (Sp6B) are two of the most common causes of IPD around the world and are more frequently isolated from infections than most of the other serotypes. Our group has previously developed a method for making immune responses to bacterial glycans T cell-dependent, involving attachment of short synthetic glycans to a virus-like nanoparticle (VLP), and in combination with a natural killer T cell (NKT cell) adjuvant. This strategy enhanced immune responses by facilitating T cell help with B cells, leading to antibody class switching and affinity maturation. The effectiveness of this vaccine model was initially demonstrated with two serotypes of Spn (Sp3 and Sp14). To further investigate this design, short synthetic glycans of Sp6A and Sp6B were synthesized as disaccharides and trisaccharides with propargyl glycosides to ensure close glycan-VLP proximity for optimal T-cell receptor recognition. Two disaccharides and two trisaccharides were successfully synthesized without using the commonly employed benzyl-protecting groups in carbohydrate chemistry.

Degree

PhD

College and Department

Computational, Mathematical, and Physical Sciences; Chemistry and Biochemistry

Rights

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

Date Submitted

2024-06-21

Document Type

Dissertation

Handle

http://hdl.lib.byu.edu/1877/etd13725

Keywords

Streptococcus pneumoniae, serotypes 6A and 6B, bacterial glycans, short synthetic glycans, propargyl glycosides

Language

english

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