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Infection and Immunity, November 2004, p. 6546-6553, Vol. 72, No. 11
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.11.6546-6553.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Enhanced Immunogenicity in the Murine Airway Mucosa with an Attenuated Salmonella Live Vaccine Expressing OprF-OprI from Pseudomonas aeruginosa

Heinz Arnold,1,{dagger} Dirk Bumann,2,{dagger},{ddagger} Melanie Felies,3 Britta Gewecke,1 Meike Sörensen,2 J. Engelbert Gessner,4 Joachim Freihorst,1 Bernd Ulrich von Specht,5 and Ulrich Baumann1*

Department of Paediatric Pulmonology and Neonatalogy,1 Department of Functional and Applied Anatomy,3 Department of Clinical Immunology, Hannover Medical School, Hannover,4 Department of Molecular Biology, Max Planck Institute for Biology of Infection, Berlin,2 Centre for Clinical Research, Freiburg University, Freiburg, Germany5

Received 13 June 2004/ Returned for modification 14 July 2004/ Accepted 2 August 2004

We constructed an oral live vaccine based on the attenuated aroA mutant Salmonella enterica serovar Typhimurium strain SL3261 expressing outer membrane proteins F and I (OprF-OprI) from Pseudomonas aeruginosa and investigated it in a mouse model. Strains with in vivo inducible protein expression with the PpacC promoter showed good infection rates and immunogenicity but failed to engender detectable antibodies in the lung. However, a systemic booster vaccination following an oral primary immunization yielded high immunoglobulin A (IgA) and IgG antibody levels in both upper and lower airways superior to conventional systemic or mucosal booster vaccination alone. In addition, the proportion of IgG1 and IgG2a antibodies suggested that the systemic booster does not alter the more TH1-like type of response induced by the oral Salmonella primary vaccination. We conclude that an oral primary systemic booster vaccination strategy with an appropriate mucosal vector may be advantageous in diseases with the risk of P. aeruginosa airway infection, such as cystic fibrosis.


* Corresponding author. Mailing address: Department of Pediatric Pulmonology and Neonatology, Hannover Medical School, 30623 Hannover, Germany. Phone: 49 511 532 3220. Fax: 49 511 532 9125. E-mail: baumann.ulrich{at}mh-hannover.de.

Editor: J. D. Clements

{dagger} H.A. and D.B. contributed equally to this work

{ddagger} Present address: Institute of Immunology, Hannover Medical School, Hannover, Germany.


Infection and Immunity, November 2004, p. 6546-6553, Vol. 72, No. 11
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.11.6546-6553.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.




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