An Antibacterial Vaccination Strategy Based on a Glycoconjugate

Vaccination with a synthetic glycoconjugate, in combination with the administration of an inhibitor that blocks capsular polysaccharide synthesis in bacteria, could offer an alternative route to combat Gram-negative bacterial infections. The strategy targets a universal epitope present in the inner-core region of cell surface lipopolysaccharide (LPS). This epitope is normally obscured by the presence of capsular polysaccharide (CPS) but supplying a simple inhibitor that blocks export of newly synthesized, intracellular CPS to the exterior of the bacterium exposes the inner core of cell wall LPS.

However, simply exposing the LPS does not kill bacteria, so the team synthesized a synthetic glycoconjugate that mimics the LPS epitope. Immunization with the synthetic glycoconjugate could then enable the production of antibodies that can bind to and neutralize the bacteria. Such a combination therapy represents an innovative evolution of attempts by others to exploit the common structural elements present in LPS as targets for antibody therapy3–9 or as vaccine components10