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PMID: 17145948 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't

Identification of candidates for a subunit vaccine against extraintestinal pathogenic Escherichia coli.

Infection and immunity ·Vol. 75 ·No. 4 ·2007-04-00 ·Pages 1916-25

Durant L, Metais A, Soulama-Mouze C, Genevard JM, Nassif X, Escaich S

Abstract

Extraintestinal pathogenic Escherichia coli (ExPEC) strains cause a large spectrum of infections. The majority of ExPEC strains are closely related to the B2 or the D phylogenetic group. The aim of our study was to develop a protein-based vaccine against these ExPEC strains. To this end, we identified ExPEC-specific genomic regions, using a comparative genome analysis, between the nonpathogenic E. coli strain K-12 MG1655 and ExPEC strains C5 (meningitis isolate) and CFT073 (urinary tract infection isolate). The analysis of these genomic regions allowed the selection of 40 open reading frames, which are conserved among B2/D clinical isolates and encode proteins with putative outer membrane localization. These genes were cloned, and recombinant proteins were purified and assessed as vaccine candidates. After immunization of BALB/c mice, five proteins induced a significant protective immunity against a lethal challenge with a clinical E. coli strain of the B2 group. In passive immunization assays, antigen-specific antibodies afforded protection to naive mice against a lethal challenge. Three of these antigens were related to iron acquisition metabolism, an important virulence factor of the ExPEC, and two corresponded to new, uncharacterized proteins. Due to the large number of genetic differences that exists between commensal and pathogenic strains of E. coli, our results demonstrate that it is possible to identify targets that elicit protective immune responses specific to those strains. The five protective antigens could constitute the basis for a preventive subunit vaccine against diseases caused by ExPEC strains.

MeSH Terms
Animals Antibodies, Bacterial/immunology Bacterial Outer Membrane Proteins/genetics,immunology Biological Transport Disease Models, Animal Escherichia coli/immunology,isolation & purification Escherichia coli Infections/immunology,microbiology,prevention & control Escherichia coli Proteins/genetics,immunology Escherichia coli Vaccines/immunology Female Genome, Bacterial Humans Immunization, Passive Mice Mice, Inbred BALB C Vaccines, Subunit/immunology Vaccines, Synthetic/genetics,immunology Virulence Factors/genetics,immunology
Chemicals
Antibodies, Bacterial Bacterial Outer Membrane Proteins Escherichia coli Proteins Escherichia coli Vaccines Vaccines, Subunit Vaccines, Synthetic Virulence Factors
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Durant Lionel
Mutabilis SA, 102 route de Noisy, 93230 Romainville, France.
Metais Arnaud
Soulama-Mouze Coralie
Genevard Jean-Marie
Nassif Xavier
Escaich Sonia
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Article Info
Journal
Infection and immunity
Abbr.
Infect Immun
ISSN
0019-9567
DOI
10.1128/IAI.01269-06
Published
2007-04-00
Epub
2006-00-04
Pages
1916-25
Language
English
Region
United States
NLM ID
0246127
PMCID
PMC1865706
Subset
IM
External Links
PubMed source DOI: 10.1128/IAI.01269-06 PMC Full Text View journal details
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