The incidence of whooping cough, once a common and deadly childhood disease, was greatly reduced following the introduction of whole-cell vaccines in the late 1940s [1]. However, concern about their side effects led to a transition to acellular vaccines in the 1980s [2]. Subsequently, the incidence of whooping cough has increased to levels 50-fold higher than the all-time low in the United States, in 1976 [3]. In many countries, even those with high vaccine coverage, B. pertussis continues to spread and cause periodic epidemics [4–9], raising questions about the effects of vaccines on the spread of disease. Acellular vaccines provide protection against the most severe forms of whooping cough but are less effective against B. pertussis infections associated with milder forms of coughing illness [1, 4]. Consequently, there is debate about whether acellular vaccines induce the most effective type of immune response to protect vaccinated individuals and prevent the spread of disease [10]. Both whole-cell and acellular vaccines are able to generate high levels of antibodies towards the bacterial components present in each. But only the whole-cell vaccine efficiently activates T-helper type 1 (Th1) cells that generate an effective interferon γ (IFN-γ) response that is important in the control and clearance of B. pertussis infection [11, 12]. Acellular vaccination creates a largely Th2 and Th17 response that is less effective in animal models, potentially explaining the increased incidence coinciding with the switch to acellular vaccines [10, 12]. To date, these analyses have been limited to studies within individuals. However, the observed differences in response would also be expected to affect the inflammatory response that could contribute to symptoms such as coughing and sneezing, the primary mechanisms of transmission of B. pertussis. Therefore, the different effects of the 2 vaccines could also contribute to the observed increase in incidence by affecting the transmission of B. pertussis, although these effects have not been measured experimentally. Detailed molecular studies of Bordetella pathogenesis have been performed in the mouse model, because of its simplicity and reproducibility, and findings have been consistent with those from the limited work done in humans and other animals [1, 13]. In many cases, Bordetella bronchiseptica, a closely related subspecies of B. pertussis that naturally infects a wide range of mammalian hosts, including humans and mice, has been used as a model system to study the infectious process [1, 14]. Since B. bronchiseptica naturally infects mice, both interactions between bacterial factors and host immune functions can be probed to the molecular level during the infectious process. These infection models have focused on the interactions between bacteria and an experimentally inoculated host, largely avoiding the defining characteristic of infectious disease: transmission. To overcome this limitation, we have recently developed a transmission system in mice, in which we have demonstrated the importance of innate immune activity regulated by Toll-like receptor 4 (TLR4) in limiting the transmission of B. bronchiseptica [15]. Defects in TLR4 led to an increase in both the infectiousness of the infected individual (ie, shedding) and the susceptibility of the host (ie, colonization of susceptible mice) in this model. Importantly, this work has provided an experimental system in which transmission can be studied experimentally, allowing direct measurement of the effects of vaccines on various aspects that contribute to transmission. In this study, we examine the effects of vaccination on transmission and examine the immune mechanisms involved in these effects. Consistent with expectations, whole-cell vaccines (involving either B. pertussis or B. bronchiseptica) induce an immune response that limits shedding and blocks transmission from inoculated index cases. Both memory CD4+ T cells and antibodies are implicated in the control of shedding. Whole-cell vaccination was effective in limiting the shedding and infectivity of B. bronchiseptica, while acellular vaccination was less effective. Together these results suggest that the resurgence of B. pertussis could be due to 2 deficiencies of the acellular vaccines: failure to protect the vaccinated individual from infection, only blunting the severity of disease, and failure to prevent the transmission of B. pertussis. The different effects of vaccines on individual and herd immunity should be important considerations for the next generation of B. pertussis vaccines.