This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Darrieux, M.
Right arrow Articles by Leite, L. C. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Darrieux, M.
Right arrow Articles by Leite, L. C. C.

 Previous Article  |  Next Article 

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:

  • Francis, J. P., Richmond, P. C., Pomat, W. S., Michael, A., Keno, H., Phuanukoonnon, S., Nelson, J. B., Whinnen, M., Heinrich, T., Smith, W.-A., Prescott, S. L., Holt, P. G., Siba, P. M., Lehmann, D., van den Biggelaar, A. H. J. (2009). Maternal Antibodies to Pneumolysin but Not to Pneumococcal Surface Protein A Delay Early Pneumococcal Carriage in High-Risk Papua New Guinean Infants. CVI 16: 1633-1638 [Abstract] [Full Text]  
  • Xin, W., Li, Y., Mo, H., Roland, K. L., Curtiss, R. III (2009). PspA Family Fusion Proteins Delivered by Attenuated Salmonella enterica Serovar Typhimurium Extend and Enhance Protection against Streptococcus pneumoniae. Infect. Immun. 77: 4518-4528 [Abstract] [Full Text]  
  • 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]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»