SUMMARY Pseudomonas aeruginosa (Pa) is an important opportunistic human pathogen that causes severe infections in patients with burns, severe wounds, pneumonia, and critically ill patients who require intubation or catheterization. Clearing Pa is difficult due to antibiotic resistance. There are ~32,600 cases of multi-drug resistant (MDR) Pa in hospitalized patients annually with 2700 deaths and $757 million in patient care costs. Additionally, Pa is the major cause of pulmonary infections in cystic fibrosis (CF) patients with >70% of this population being chronically colonized by their teens. Military personnel are gravely impacted by the occurrence of MDR Pa in combat-related injuries. Equally important is the fact that the biggest risk factor for negative outcomes associated with infection by MDR Pa is advanced age. After age 60, there is a significant increase in morbidity and mortality resulting from MDR Pa infection. Thus, a broadly protective Pa vaccine has large market potential with up to three vaccinations providing complete protection to all humans. Hundreds of millions of vaccine doses would be given annually, approaching ~$5B in sales. While there are Pa vaccines in development, none have been licensed. The goal of our technology is a prophylactic vaccine that prevents initial colonization by Pa, regardless of serotype, to protect vulnerable patients, which we are targeting as mature adults for this study, prior to biofilm formation and host adaptation. When Phase I is completed, we will have optimized the vaccine formulation and demonstrated protective efficacy in mice and rabbit models.