Abstract Development of effective vaccines requires logical design and formulation of two main components: antigens and adjuvants. Some compounds, called immunogens, can assume both of these roles. Notably, Bordetella pertussis (Bp) and some of its antigenic products have been found to adjuvant immune responses to other vaccines or vaccine components. We chose to explore this ability by using B. pertussis and pertussis toxin as adjuvants for a whole cell vaccine (WCV) against Pseudomonas aeruginosa (Pa). Pa is a highly antibiotic resistant Gram-negative opportunistic pathogen for which there are no approved vaccines or immunotherapies. We formulated vaccines containing Pa with Bp or pertussis toxin to determine if these components could modulate the immune response to PaWCV, as measured by quantification of bacterial burden and immune cell response after an acute pneumonia challenge. We determined that these additions to the PaWCV were associated with increased clearance of bacteria after challenge and increased Pa-binding immunoglobulins in the blood and airway. Additionally, we determined that the BpWCV alone was sufficient to induce protection from acute Pa infection. This correlated with production of antibodies that bind Pa, indicating that there is at least one cross-reactive antigen that could be providing protection. Through utilization of immunoblotting of protein fractions of Pa and mass spectroscopy, we identified this protective antigen. It will be used to formulate a subunit vaccine and tested for efficacy in protection from Pseudomonas infection. This type of cross-protection is novel within the field and could lead to the identification of a protective antigen against P. aeruginosa in B. pertussis.