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Clinical and Vaccine Immunology, March 2008, p. 522-533, Vol. 15, No. 3
1071-412X/08/$08.00+0     doi:10.1128/CVI.00432-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Rational Combination of Peptides Derived from Different Mycobacterium leprae Proteins Improves Sensitivity for Immunodiagnosis of M. leprae Infection{triangledown} ,{dagger}

Annemieke Geluk,1* Jolien van der Ploeg,1 Rose O. B. Teles,2 Kees L. M. C. Franken,1 Corine Prins,1 Jan Wouter Drijfhout,1 Euzenir N. Sarno,2 Elizabeth P. Sampaio,2 and Tom H. M. Ottenhoff1

Department of Infectious Diseases/Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands,1 Leprosy Laboratory, Department of Immunology, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, Brazil2

Received 30 October 2007/ Returned for modification 20 November 2007/ Accepted 8 January 2008

The stable incidence of new leprosy cases suggests that transmission of infection is continuing despite the worldwide implementation of multidrug therapy programs. Highly specific tools are required to accurately diagnose asymptomatic and early stage Mycobacterium leprae infections which are the likely sources of transmission and cannot be identified by using the detection of antibodies against phenolic glycolipid I. One of the hurdles hampering T-cell-based diagnostic tests is that M. leprae antigens cross-react at the T-cell level with antigens present in other mycobacteria, like M. tuberculosis or M. bovis bacillus Calmette-Guerin (BCG). Using comparative genomics, we previously identified five candidate proteins highly restricted to M. leprae which showed promising features with respect to application in leprosy diagnostics. However, despite the lack of overall sequence homology, the use of recombinant proteins includes the risk of detecting T-cell responses that are cross-reactive with other antigens. To improve the diagnostic potential of these M. leprae sequences, we used 50 synthetic peptides spanning the sequences of all five proteins for the induction of T-cell responses (gamma interferon) in leprosy patients, healthy household contacts (HHC) of leprosy patients, and healthy controls in Brazil, as well as in tuberculosis patients, BCG vaccinees, and healthy subjects from an area of nonendemicity. Using the combined T-cell responses toward four of these peptides, all paucibacillary patients and 13 out of 14 HHC were detected without compromising specificity. The peptides contain HLA binding motifs for various HLA class I and II alleles, thereby meeting an important requirement for the applicability of diagnostic tools in genetically diverse populations. Thus, this study provides the first evidence for the possibility of immunodiagnostics for leprosy based on mixtures of peptides recognized in the context of different HLA alleles.

* Corresponding author. Mailing address: Department of Infectious Diseases, LUMC, P.O. Box 9600, 2300 RC Leiden, The Netherlands. Phone: 31-71-526-3844. Fax: 31-71-526-5267. E-mail: a.geluk{at}lumc.nl

{triangledown} Published ahead of print on 16 January 2008.

{dagger} Supplemental material for this article may be found at http://cvi.asm.org/.

Clinical and Vaccine Immunology, March 2008, p. 522-533, Vol. 15, No. 3
1071-412X/08/$08.00+0     doi:10.1128/CVI.00432-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Geluk, A., Spencer, J. S., Bobosha, K., Pessolani, M. C. V., Pereira, G. M. B., Banu, S., Honore, N., Reece, S. T., MacDonald, M., Sapkota, B. R., Ranjit, C., Franken, K. L. M. C., Zewdie, M., Aseffa, A., Hussain, R., Stefani, M. M., Cho, S.-N., Oskam, L., Brennan, P. J., Dockrell, H. M., on behalf of the IDEAL Consortium, (2009). From Genome-Based In Silico Predictions to Ex Vivo Verification of Leprosy Diagnosis. CVI 16: 352-359 [Abstract] [Full Text]  
  • Duthie, M. S., Goto, W., Ireton, G. C., Reece, S. T., Sampaio, L. H., Grassi, A. B., Sousa, A. L. M., Martelli, C. M. T., Stefani, M. M. A., Reed, S. G. (2008). Antigen-Specific T-Cell Responses of Leprosy Patients. CVI 15: 1659-1665 [Abstract] [Full Text]  


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