SUMMARY Bordetella pertussis causes one of the most important human diseases, Pertussis or Whooping Cough, infecting tens of millions and killing hundreds of thousands of children annually. Although vaccines available in most industrialized countries are reasonably effective in preventing death and the most severe forms of disease, there is growing appreciation that the current acellular vaccines fail to prevent colonization, bacterial shedding and transmission between hosts, which allows B. pertussis to continue to circulate and cause disease and death in the most susceptible groups. There is little understanding of the mechanistic basis for transmission, either in terms of bacterial factors or host immune functions involved, and consequently, there is no agreed upon strategy to interfere with its ongoing circulation. Excitingly, recent work in our group now allows detailed analysis of the initial and highly contagious “catarrhal phase” of the infection that is crucial for transmission of the pathogen and spread of the disease. Based on our novel mouse model of B. pertussis infection, that reproduces the catarrhal phase in mice, we will identify the bacterial factors that trigger host inflammatory response, mucus secretion and bacterial shedding and the factors required for the colonization of a new host. We will evaluate these factors for their potential to stimulate a robust host immune response and assess these proteins or epitopes thereof as vaccine components to prevent bacterial transmission. Supplementation of the currently used pertussis vaccines with these newly identified bacterial “transmission factors” will not only protect against the disease but also block the rampant spread of the pathogen.