This study examines the safety and immunogenicity of an oral, whole-cell vaccine administered to healthy volunteers. of the study did not show any vaccine-attributable adverse effects in any of the subjects, as documented by clinical evidence, hematology, and biochemistry profiles. We conclude that Pseudostat is safe and immunogenic in humans at this dose and that further studies to determine the appropriate dosage and efficacy are needed. In our study, we have shown that the most significant and sustained responses to oral vaccination in human adult volunteers were serum IgA levels and that pooled sera collected postimmunization have an increased capacity to promote opsonophagocytotic killing of is a gram-negative bacterium with a ubiquitous distribution within the biosphere. In the compromised host, it is capable of establishing CUDC-101 opportunistic infections, and this is particularly common in subjects with lung CUDC-101 dysfunction. is CUDC-101 particularly well adapted to the conditions found in the CUDC-101 lungs of cystic fibrosis (CF) patients, where a defective chloride channel transport protein results in an increased viscosity of secretions, making it difficult to clear airway mucous. Colonization takes place at an early age, often in the absence of any overt clinical presentation or culture-positive sputum and throat swabs (3). Because the bacteria are not effectively eradicated from the CF lungs, CUDC-101 chronic colonization occurs. adapts through gene switching to undergo a number of phenotypic changes. These include the loss of lipopolysaccharide (LPS) O antigen, which renders the strain nontypeable or polyagglutinating, and the production of excessive amounts of an alginate polysaccharide capsule (14), which allows the microbe to exist in microcolonies (biofilms) within the lungs. In addition, these nontypeable, mucoid colonies exhibit a reduced susceptibility to antibiotics and frustrated phagocytosis, where excessive amounts of alginate prevent phagocytosis by polymorphonuclear neutrophils and macrophages. The resulting excessive production of proteases, superoxide radicals, and inflammatory mediators contributes to the subsequent destruction of normal lung tissue. The major antigen of immune complexes in the sputum of CF patients has been shown to be LPS (17). Outer membrane protein F (OprF) and outer membrane protein H2 (OprH2) in particular have been shown to induce strong antibody activity, while OprI, OprF, and OprH2 are highly conserved in (31, 33). Current therapies with antibiotics are targeted at controlling bacterial load of and other bacteria. These frequently fail to adequately clear established infections, while low antibiotic concentrations in the airways are ineffective and may lead to the development of resistant bacterial strains. A vaccine which could prevent or delay initial colonization with in the lungs may have a positive impact on CF patients and contribute to improvement in quality of life and survival in these patients. In addition, it is also feasible that immunization may reduce bacterial loads in patients who have become chronically colonized with have been under study for some 30 years or more, but progress has been slow (9). The potential to vaccinate against infection has been recently reviewed, and a number of exciting opportunities have been identified including mucosal immunization (27). Most studies have focused on burn patients and CF patients, and many havenot progressed beyond initial proof-of-concept stages. ACochranereview in 1999 (16) concluded that there was a paucity of randomized medical trials assessing the effectiveness of vaccination against in CF individuals. The only trial to meet their inclusion criteria was one evaluating a blended LPS given NR4A3 to children, which showed no medical benefit in the 10-12 months follow-up. There was also a suggestion the vaccine may have been detrimental, with the immunized group appearing to have more severe pulmonary exacerbations than the control group (18). Although this does not preclude a vaccine approach to illness in the management of CF, it may possess added to the reluctance and sluggish progress in developing.