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Infection and Immunity, December 2007, p. 5930-5938, Vol. 75, No. 12
0019-9567/07/$08.00+0     doi:10.1128/IAI.00940-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Fusion Proteins Containing Family 1 and Family 2 PspA Fragments Elicit Protection against Streptococcus pneumoniae That Correlates with Antibody-Mediated Enhancement of Complement Deposition{triangledown}

M. Darrieux,1 E. N. Miyaji,1 D. M. Ferreira,1 L. M. Lopes,1 A. P. Y. Lopes,1 B. Ren,2 D. E. Briles,2 S. K. Hollingshead,2 and L. C. C. Leite1*

Centro de Biotecnologia, Insituto Butantan, São Paulo, Brazil,1 Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama2

Received 10 July 2007/ Returned for modification 23 August 2007/ Accepted 27 September 2007

PspA is an important pneumococcal vaccine candidate that is capable of inducing protection in different animal models. Because of its structural diversity, a PspA-based vaccine should contain at least one fragment from each of the two major families (1 and 2) in order to elicit broader protection. In the present work, we have tested the potential of PspA hybrids containing fused portions of family 1 and 2 (PspA1ABC-4B and PspA1ABC-3AB) PspA fragments to induce protection against pneumococci bearing distinct PspA fragments. Sera from mice immunized with these hybrid PspA fragments were able to increase C3 deposition on pneumococci bearing PspA fragments from both families, in contrast with sera made against the PspA family 1 (PspA1ABC) and PspA family 2 (PspA3ABC) fragments, which were effective only within the same family. Although PspA hybrids were able to extend protection against pneumococcal infection with strains bearing diverse PspA fragments, the immunity elicited by family 2 was clade dependent, suggesting that PspA fragments from family 2 clades 3 and 4 should both be included in a comprehensive PspA vaccine. These results indicate that PspA fusion proteins constitute an efficient immunization strategy for future PspA-based antipneumococcal vaccines since they are able to extend protection provided by a protein derived from a single transcript.

* Corresponding author. Mailing address: Centro de Biotecnologia, Instituto Butantan, Av. Vital Brasil 1500, 05509-900 São Paulo, SP, Brazil. Phone: 55-11-3726-7222, ext. 2242. Fax: 55-11-3726-9150. E-mail: lccleite{at}butantan.gov.br

{triangledown} Published ahead of print on 8 October 2007.

Editor: J. N. Weiser

Infection and Immunity, December 2007, p. 5930-5938, Vol. 75, No. 12
0019-9567/07/$08.00+0     doi:10.1128/IAI.00940-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Melin, M. M., Hollingshead, S. K., Briles, D. E., Lahdenkari, M. I., Kilpi, T. M., Kayhty, H. M. (2008). Development of Antibodies to PspA Families 1 and 2 in Children after Exposure to Streptococcus pneumoniae. CVI 15: 1529-1535 [Abstract] [Full Text]  
  • Ferreira, D. M., Darrieux, M., Oliveira, M. L. S., Leite, L. C. C., Miyaji, E. N. (2008). Optimized Immune Response Elicited by a DNA Vaccine Expressing Pneumococcal Surface Protein A Is Characterized by a Balanced Immunoglobulin G1 (IgG1)/IgG2a Ratio and Proinflammatory Cytokine Production. CVI 15: 499-505 [Abstract] [Full Text]  
  • Darrieux, M., Moreno, A. T., Ferreira, D. M., Pimenta, F. C., de Andrade, A. L. S. S., Lopes, A. P. Y., Leite, L. C. C., Miyaji, E. N. (2008). Recognition of pneumococcal isolates by antisera raised against PspA fragments from different clades. J Med Microbiol 57: 273-278 [Abstract] [Full Text]  


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