Sweet Immunization

Summary

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As bacteria become increasingly resistant to antibiotics, new ways to prevent infections are urgently needed. One promising approach is to develop vaccines that target sugars (called glycans) found on the surface of bacteria. These glycans help protect bacteria and interact with the host’s immune system. Current bacterial glycan vaccines target the outer “sugar coat”, —called capsules. However, capsules can vary greatly within a bacterial species and vaccination using a single capsule type does not provide broad protection.

This thesis focused on a different type of streptococcal surface sugar, called rhamnose-rich polysaccharide (RPS), which is more conserved across strains and may be a better target for universal vaccines. Two bacteria were studied in detail: Streptococcus suis, a pig pathogen that can also infect humans, and Streptococcus uberis, which causes udder infections in cows.

In S. suis, a conserved RPS “core” glycan structure was identified that was similar across different pathogenic strains. When pigs were immunized with this “core” glycan structure, they produced antibodies that recognized many different types of S. suis. Similarly, in S. uberis, a sugar backbone known as rhamnan was found to be widely expressed in S. uberis strains and was recognized by cow antibodies, suggesting it could serve as a vaccine target.

The research also uncovered that both S. suis and S. uberis RPS are negatively charged because they carry a special chemical group called glycerol phosphate. The gene responsible for adding this chemical group to RPS was identified in this thesis.

Altogether, this thesis provides new insights into the development of next-generation glycan vaccines, whereby shared-glycan motifs could overcome antigenic diversity and protect against genetically diverse streptococcal pathogens.