Enhanced immunogenicity in the murine airway mucosa with an attenuated Salmonella live vaccine expressing OprF-OprI from Pseudomonas aeruginosa

Heinz Arnold; Dirk Bumann; Melanie Felies; Britta Gewecke; Meike Sörensen; J Engelbert Gessner; Joachim Freihorst; Bernd Ulrich von Specht; Ulrich Baumann

doi:10.1128/IAI.72.11.6546-6553.2004

Enhanced immunogenicity in the murine airway mucosa with an attenuated Salmonella live vaccine expressing OprF-OprI from Pseudomonas aeruginosa

Infect Immun. 2004 Nov;72(11):6546-53. doi: 10.1128/IAI.72.11.6546-6553.2004.

Authors

Heinz Arnold¹, Dirk Bumann, Melanie Felies, Britta Gewecke, Meike Sörensen, J Engelbert Gessner, Joachim Freihorst, Bernd Ulrich von Specht, Ulrich Baumann

Affiliation

¹ Department of Pediatric Pulmonology and Neonatology, Hannover Medical School, 30623, Germany.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Administration, Oral
Animals
Antibodies, Bacterial / analysis
Antibodies, Bacterial / blood
Bacterial Proteins / administration & dosage
Bacterial Proteins / genetics
Bacterial Proteins / immunology*
Bacterial Vaccines / genetics
Bacterial Vaccines / immunology*
Humans
Immunity, Mucosal
Lipoproteins / administration & dosage
Lipoproteins / genetics
Lipoproteins / immunology*
Male
Mice
Mice, Inbred C57BL
Porins / administration & dosage
Porins / genetics
Porins / immunology*
Pseudomonas Infections / prevention & control
Pseudomonas aeruginosa / immunology*
Recombinant Fusion Proteins / immunology
Recombinant Fusion Proteins / metabolism
Respiratory Mucosa / immunology*
Salmonella typhimurium / genetics*
Salmonella typhimurium / immunology
Vaccination
Vaccines, Attenuated / genetics
Vaccines, Attenuated / immunology
Vaccines, Synthetic / immunology

Substances

Antibodies, Bacterial
Bacterial Proteins
Bacterial Vaccines
Lipoproteins
Porins
Recombinant Fusion Proteins
Vaccines, Attenuated
Vaccines, Synthetic
outer membrane lipoprotein I, Bacteria