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Infection and Immunity, May 2004, p. 2659-2670, Vol. 72, No. 5
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.5.2659-2670.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Prevention of Pneumococcal Disease in Mice Immunized with Conserved Surface-Accessible Proteins

Josée Hamel,^* Nathalie Charland, Isabelle Pineau, Catherine Ouellet, Stéphane Rioux, Denis Martin, and Bernard R. Brodeur

Unité de Recherche en Vaccinologie, Centre de Recherche du Centre Hospitalier Universitaire de Québec, Pavillon CHUL, Sainte-Foy, Québec G1V 4G2, Canada

Received 9 December 2003/ Returned for modification 15 January 2004/ Accepted 21 January 2004

The development of a vaccine against Streptococcus pneumoniae has been complicated by the existence of at least 90 antigenically distinct capsular serotypes. Common protein-based vaccines could represent the best strategy to prevent pneumococcal infections, regardless of serotype. In the present study, the immunoscreening of an S. pneumoniae genomic library allowed the identification of a novel immune protein target, BVH-3. We demonstrate that immunization of mice with BVH-3 elicits protective immunity against experimental sepsis and pneumonia. Sequence analysis revealed that the bvh-3 gene is highly conserved within the species. Since the BVH-3 protein shows homology at its amino-terminal end with other pneumococcal proteins, it was of interest to determine if protection was due to the homologous or to the protein-specific regions. Immunoprotection studies using recombinant BVH-3 and BVH-3-related protein fragments as antigens allowed the localization of surface-exposed and protective epitopes at the protein-specific carboxyl termini, thus establishing that BVH-3 is distinct from other previously reported protective protein antigens. Immunization with a chimeric protein comprising the carboxyl-terminal regions of BVH-3 and of a BVH-3-related protein improved the protection by targeting two surface pneumococcal components. Thus, BVH-3 and the chimeric protein hold strong promise as vaccine components to control pneumococcal disease.

Editor: J. N. Weiser

Present address: Centre de Recherche de Cardiologie, Hôpital Laval, 2725 Chemin Ste-Foy, Ste-Foy, Québec, Canada G1V 4G5.

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