Grant: Project Grant

Bordetella pertussis, the causative agent of whooping cough can alter a component of its surface structure called lipid A to either increase or dampen host responses to it. We will investigate the mechanisms by which small changes in B. pertussis lipid A influence how it is engaged by the host cell and how this interaction affects signaling responses and the production of immune molecules called cytokines. The amount and pattern of cytokines produced can shape the outcome of an infection. We will also examine the influence of engineered lipid A changes on B. pertussis pathogenesis in a humanized mouse model of infection. This work also has implications for improving the whooping cough vaccine. There is a growing concern that the duration of protection from the current protein-based whooping cough vaccines does not last very long and this may be attributed to the complete removal of lipid A, something that was done to eliminate the endotoxicity of the whole-cell vaccine. Manipulating B. pertussis to produce an altered lipid A may ultimately result in an inexpensive, killed whole-cell vaccine that produces fewer fevers yet is potent enough to elicit a longer lasting immune response to stop the spread of whooping cough.