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

被引:59
作者
DiGiandomenico, Antonio
Rao, Jayasimha
Harcher, Katie
Zaidi, Tanweer S.
Gardner, Jason
Neely, Alice N.
Pier, Gerald B.
Goldberg, Joanna B.
机构
[1] Univ Virginia, Dept Microbiol, Hlth Syst, Charlottesville, VA 22908 USA
[2] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA
[3] Shriners Hosp Children, Cincinnati, OH 45229 USA
关键词
antibody; Salmonella; vaccine;
D O I
10.1073/pnas.0608657104
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 [理学]; 0710 [生物学]; 09 [农学];
摘要
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 0 antigen portion of Pseudomonas aeruginosa lipopolysaccharide. A 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 A 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.
引用
收藏
页码:4624 / 4629
页数:6
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