Carbohydrates are ubiquitous in nature. On the surface of bacterial cells, there are many carbohydrate antigens, which are attractive targets for next generation vaccine development. However, a significant challenge in developing carbohydrate-based vaccines is their low immunogenecities. Direct administration of carbohydrates cannot elicit a powerful antibody response to protect the host from diseases. In this presentation, we will present our strategies to significantly enhance the immunogenicity of carbohydrate antigens, using Bordetella pertussis (B. pertussis) associated glycans as a representative antigen.
B. pertussis infections are a major public health problem throughout the world. While there is a vaccine against this bacterium, the current vaccine only mitigates the symptoms, not killing the bacteria. Furthermore, the number of B. pertussis cases has risen significantly during the past two decades suggesting the urgent need for new vaccines. Lipopolysaccharide (LPS) of B. pertussis is an attractive antigen for vaccine development. With the presence of multiple rare sugars and unusual glycosyl linkages, B. pertussis LPS is a highly challenging synthetic target. Aided by molecular dynamics simulation and modeling, the LPS like pentasaccharide was chemically synthesized for the first time. The pentasaccharide was conjugated with a powerful carrier, bacteriophage Qβ as a vaccine candidate. Immunization of mice with the conjugate induced robust anti-glycan IgG responses with IgG titers reaching several million enzyme-linked immunosorbent assay (ELISA) units. The antibodies generated were long lasting and boostable, and could recognize multiple clinical strains of B. pertussis, highlighting the potential of Qβ-glycan as a new anti-pertussis vaccine.

Rajendar Deora

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