OUTER-MEMBRANE PROTEINS OF PSEUDOMONAS-AERUGINOSA AS VACCINE CANDIDATES

We tested the ability of the recombinant outer membrane proteins of Ps eudomonas aeruginosa to serve as a protective vaccine against this Gra m-negative pathogen in the presence of two main pathophysiological eve nts leading to P. aeruginosa sepsis: (i) systemic infection during imm unosuppression; and (ii) bacterial translocation. A hybrid vaccine was cloned which combined the protective epitopes of outer membrane prote in F (OprF) and outer membrane protein I (OprI). This vaccine proved t o be highly protective against an intraperitoneal challenge with P. ae ruginosa in immunosuppressed mice. Oral immunization of mice with reco mbinant OprI expressing Salmonella dublin, induced s-IgA antibodies in the gut mucosa against OprI. These provided protection against transl ocation of P. aeruginosa in an immunosuppressed mouse model. To test w hether OprI is effective in man, recombinant OprI was purified and use d for the immunization of human volunteers. Immunization was tolerated well, and no side effects were observed. Antibody titers against OprI were measured in 90% of the volunteers after immunization.