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
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
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 Majlessi, L.
Right arrow Articles by Leclerc, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Majlessi, L.
Right arrow Articles by Leclerc, C.

 Previous Article  |  Next Article 

Infection and Immunity, April 2006, p. 2128-2137, Vol. 74, No. 4
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.4.2128-2137.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

An Increase in Antimycobacterial Th1-Cell Responses by Prime-Boost Protocols of Immunization Does Not Enhance Protection against Tuberculosis

Laleh Majlessi,1* Marcela Simsova,2 Zdenka Jarvis,2 Priscille Brodin,3 Marie-Jésus Rojas,1 Cécile Bauche,4 Clémence Nouzé,1 Daniel Ladant,4 Stewart T. Cole,3 Peter Sebo,2 and Claude Leclerc1

Unité de Biologie des Régulations Immunitaires, Inserm, E 352, Institut Pasteur, Paris F-75015, France,1 Laboratory of Molecular Biology of Bacterial Pathogens, Institute of Microbiology of the Academy of Sciences of the Czech Republic, Prague, Czech Republic,2 Unité de Génétique Moléculaire Bactérienne, Institut Pasteur, Paris F-75015, France,3 Unité deBiochimie des Interactions Macromoléculaires, Institut Pasteur, Paris F-75015, France4

Received 2 September 2005/ Returned for modification 26 October 2005/ Accepted 11 January 2006

Bordetella pertussis adenylate cyclase (CyaA) toxoid is a powerful nonreplicative immunization vector targeting dendritic cells, which has already been used successfully in prophylactic and therapeutic vaccination in various preclinical animal models. Here, we investigated the potential of CyaA, harboring strong mycobacterial immunogens, i.e., the immunodominant regions of antigen 85A or the complete sequence of the 6-kDa early secreted antigenic target (ESAT-6) protein, to induce antimycobacterial immunity. By generating T-cell hybridomas or by using T cells from mice infected with mycobacteria, we first demonstrated that the in vitro delivery of 85A or ESAT-6 to antigen-presenting cells by CyaA leads to processing and presentation, by major histocompatibility complex class II molecules, of the same epitopes as those displayed upon mycobacterial infection. Importantly, compared to the recombinant protein alone, the presentation of ESAT-6 in vitro was 100 times more efficient upon its delivery to antigen-presenting cells in fusion to CyaA. Immunization with CyaA-85A or CyaA-ESAT-6 in the absence of any adjuvant induced strong antigen-specific lymphoproliferative, interleukin-2 (IL-2) and gamma interferon (IFN-{gamma}) cytokine responses, in the absence of any IL-4 or IL-5 production. When used as boosters after priming with a BCG expressing ESAT-6, the CyaA-85A and CyaA-ESAT-6 proteins were able to strikingly increase the sensitivity and intensity of proliferative and Th1-polarized responses and notably the frequency of antigen-specific IFN-{gamma}-producing CD4+ T cells. However, immunization with these CyaA constructs as subunit vaccines alone or as boosters did not allow induction or improvement of protection against Mycobacterium tuberculosis infection. These results question the broadly admitted correlation between the frequency of IFN-{gamma}-producing CD4+ T cells and the level of protection against tuberculosis.

* Corresponding author. Mailing address: Biologie des Régulations Immunitaires, Inserm, E 352, Institut Pasteur, 25 rue du Docteur Roux, 75724 Paris Cedex 15, France. Phone: 01 45 68 85 42. Fax: 01 45 68 85 40. E-mail: lmajless{at}pasteur.fr.

Editor: J. L. Flynn

Infection and Immunity, April 2006, p. 2128-2137, Vol. 74, No. 4
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.4.2128-2137.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Thacker, T. C., Palmer, M. V., Waters, W. R. (2009). T-Cell mRNA Expression in Response to Mycobacterium bovis BCG Vaccination and Mycobacterium bovis Infection of White-Tailed Deer. CVI 16: 1139-1145 [Abstract] [Full Text]  
  • Bertholet, S., Ireton, G. C., Kahn, M., Guderian, J., Mohamath, R., Stride, N., Laughlin, E. M., Baldwin, S. L., Vedvick, T. S., Coler, R. N., Reed, S. G. (2008). Identification of Human T Cell Antigens for the Development of Vaccines against Mycobacterium tuberculosis. J. Immunol. 181: 7948-7957 [Abstract] [Full Text]  
  • Soares, A. P., Scriba, T. J., Joseph, S., Harbacheuski, R., Murray, R. A., Gelderbloem, S. J., Hawkridge, A., Hussey, G. D., Maecker, H., Kaplan, G., Hanekom, W. A. (2008). Bacillus Calmette-Guerin Vaccination of Human Newborns Induces T Cells with Complex Cytokine and Phenotypic Profiles. J. Immunol. 180: 3569-3577 [Abstract] [Full Text]  
  • Majlessi, L., Combaluzier, B., Albrecht, I., Garcia, J. E., Nouze, C., Pieters, J., Leclerc, C. (2007). Inhibition of Phagosome Maturation by Mycobacteria Does Not Interfere with Presentation of Mycobacterial Antigens by MHC Molecules. J. Immunol. 179: 1825-1833 [Abstract] [Full Text]  
  • Mittrucker, H.-W., Steinhoff, U., Kohler, A., Krause, M., Lazar, D., Mex, P., Miekley, D., Kaufmann, S. H. E. (2007). Poor correlation between BCG vaccination-induced T cell responses and protection against tuberculosis. Proc. Natl. Acad. Sci. USA 104: 12434-12439 [Abstract] [Full Text]  
  • Ryan, A. A., Spratt, J. M., Britton, W. J., Triccas, J. A. (2007). Secretion of Functional Monocyte Chemotactic Protein 3 by Recombinant Mycobacterium bovis BCG Attenuates Vaccine Virulence and Maintains Protective Efficacy against M. tuberculosis Infection. Infect. Immun. 75: 523-526 [Abstract] [Full Text]  
  • Hervas-Stubbs, S., Majlessi, L., Simsova, M., Morova, J., Rojas, M.-J., Nouze, C., Brodin, P., Sebo, P., Leclerc, C. (2006). High Frequency of CD4+ T Cells Specific for the TB10.4 Protein Correlates with Protection against Mycobacterium tuberculosis Infection. Infect. Immun. 74: 3396-3407 [Abstract] [Full Text]  


Copyright © 2010 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»