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Infection and Immunity, April 2007, p. 1916-1925, Vol. 75, No. 4
0019-9567/07/$08.00+0     doi:10.1128/IAI.01269-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Identification of Candidates for a Subunit Vaccine against Extraintestinal Pathogenic Escherichia coli ^,

Mutabilis SA, 93230 Romainville,¹ Unité INSERM 570, Faculté de médecine Necker-Enfants Malades, 75015 Paris, France²

Received 8 August 2006/ Returned for modification 22 September 2006/ Accepted 20 November 2006

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.

Published ahead of print on 4 December 2006.

Editor: A. D. O'Brien

Supplemental material for this article may be found at http://iai.asm.org/.

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