Consequences of the expression of lipopolysaccharide-modifying enzymes for the efficacy and reactogenicity of whole-cell pertussis vaccines

Abstract

Lipopolysaccharide is one of the major constituents of the Gram-negative bacterial outer membrane and is, due to its endotoxic activity, responsible for the relatively high reactogenicity of whole-cell vaccines. In addition, lipopolysaccharide has strong immune stimulating properties, which makes it, potentially, an interesting vaccine component. In a previous study, we have shown that expression of two lipopolysaccharide-modifying enzymes, i.e., PagP and PagL, modulates the endotoxic activity of the Gram-negative bacterium Bordetella pertussis, the causative agent of whooping cough. To assess the consequences of PagP and PagL expression on the efficacy and reactogenicity of whole-cell pertussis vaccines, we have immunised mice and challenged them intranasally with wild-type B. pertussis. Vaccine efficacy, B. pertussis-specific antibody responses, and cytokine profiles were evaluated. The results show that expression of PagL, but not of PagP, significantly increases vaccine efficacy without altering vaccine reactogenicity. Therefore, PagL-expressing B. pertussis strains may form a basis for the development of a new and safer whole-cell pertussis vaccine, as higher vaccine efficacies may allow a reduced vaccine dosage. These data show, for the first time, that lipopolysaccharide composition is an important determinant for the efficacy of whole-cell pertussis vaccines.