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Intranasal immunization with heterologously expressed polysaccharide protects against multiple Pseudomonas aeruginosa infections

DiGiandomenico, Antonio, Rao, Jayasimha, Harcher, Katie, Zaidi, Tanweer S., Gardner, Jason, Neely, Alice N., Pier, Gerald B., Goldberg, Joanna B.
Proceedings of the National Academy of Sciences of the United States of America 2007 v.104 no.11 pp. 4624-4629
Pseudomonas aeruginosa, Salmonella Typhimurium, animal models, bacteria, cornea, genetic vectors, immune response, lipopolysaccharides, mice, pathogens, pneumonia, recombinant antigens, vaccination, vaccine development
Surface-expressed bacterial polysaccharides are often immunodominant, protective antigens. However, these antigens are chemically and serologically highly heterogeneous, and conjugation to protein carriers is often necessary to enhance their immunogenicity. Here we show the efficacy of intranasal immunization of mice with attenuated Salmonella enterica serovar Typhimurium expressing the O antigen portion of Pseudomonas aeruginosa lipopolysaccharide. P. aeruginosa is an ideal model system because it can cause a myriad of localized and systemic infections. In particular, this bacterium is a leading cause of hospital-acquired pneumonia and is responsible for infections after burns and after eye injury. In addition, there are mouse models of infection that mimic the clinical manifestations of P. aeruginosa infections. Immunized mice were highly protected against infection, with long-lasting immunity to acute P. aeruginosa pneumonia, whereas mice immunized with Salmonella containing only the cloning vector or PBS were not. Prophylactic and therapeutic administration of sera from vaccinated animals protected naive mice. Intranasal vaccination also provided complete protection from infections after burns and reduced pathology after corneal abrasions. These results indicate that intranasal delivery of heterologously expressed polysaccharide antigens provides protection at distinct sites of infection. This approach for the expression and delivery of polysaccharide antigens as recombinant immunogens could be easily adapted to develop vaccines for many infectious agents, without the need for complicated purification and conjugation procedures.