Development of carbohydrate based next-generation anti-pertussis vaccines

Abstract

Pertussis is a highly contagious respiratory disease caused by the Gram-negative bacterial pathogen, Bordetella pertussis. Despite high global vaccination rates, pertussis is resurging worldwide. Here we discuss the development of current pertussis vaccines and their limitations, which highlight the need for new vaccines that can protect against the disease and prevent development of the carrier state, thereby reducing transmission. The lipo-oligosaccharide of Bp is an attractive antigen for vaccine development as the anti-glycan antibodies could have bactericidal activities. The structure of the lipo-oligosaccharide has been determined and its immunological properties analyzed. Strategies enabling the expression, isolation, and bioconjugation have been presented. However, obtaining the saccharide on a large scale with high purity remains one of the main obstacles. Chemical synthesis provides a complementary approach to accessing the carbohydrate epitopes in a pure and structurally well-defined form. The first total synthesis of the non-reducing end pertussis pentasaccharide is discussed. The conjugate of the synthetic glycan with a powerful immunogenic carrier, bacteriophage Qβ, results in high levels and long-lasting anti-glycan IgG antibodies, paving the way for the development of a new generation of anti-pertussis vaccines with high bactericidal activities and biocompatibilities.

Keywords: Bordetella Pertussis; Lipo-oligosaccharide; Synthesis; Vaccines.