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Clinical and Vaccine Immunology, November 2008, p. 1659-1665, Vol. 15, No. 11
1071-412X/08/$08.00+0     doi:10.1128/CVI.00234-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Antigen-Specific T-Cell Responses of Leprosy Patients {triangledown}

Malcolm S. Duthie,1,2* Wakako Goto,1 Greg C. Ireton,1 Stephen T. Reece,1 Lucas H. Sampaio,3 A. B. Grassi,3 Ana Lucia M. Sousa,3 Celina M. T. Martelli,3 Mariane M. A. Stefani,3 and Steven G. Reed1

Infectious Disease Research Institute, 1124 Columbia St., Suite 400, Seattle, Washington 98104,1 Protein AI, 1102 Columbia St., Seattle, Washington 98104,2 Tropical Pathology and Public Health Institute, Federal University of Goiás, Goiânia, Brazil3

Received 19 June 2008/ Returned for modification 1 August 2008/ Accepted 2 September 2008

The identification of human T-cell antigens of Mycobacterium leprae could improve treatment and help to disrupt the transmission of leprosy by directing diagnosis and vaccine programs. This study screened a panel of M. leprae recombinant proteins for T-cell recall responses, measured by gamma interferon (IFN-{gamma}) production, among leprosy patients. After initial studies using peripheral blood mononuclear cells from leprosy patients, we transitioned our studies to simple whole-blood assays (WBA), which are more applicable in field or clinical settings. T-cell responses generated in WBA using blood from individuals in Goiânia, Brazil, demonstrated that several M. leprae antigens (ML0276, ML0840, ML1623, ML2044, and 46f) elicited >0.5 IU/ml IFN-{gamma}, and these proteins were classified as immunogenic and leprosy specific. Several of these individual antigens were recognized by cells from >60% of Brazilian paucibacillary (PB) leprosy patients, and ML0276, ML0840, ML1623, and 46f complemented each other such that 82% of PB patients had strong (>1.25 IU/ml IFN-{gamma}) responses to at least one of these proteins. These proteins were also recognized by cells from a significant proportion of the household contacts of multibacillary leprosy patients, but in contrast, few responses were observed in active tuberculosis patients or healthy control groups from areas of endemicity. Our results indicate several potential candidate antigens which may be useful for either leprosy diagnosis or vaccination and demonstrate the utility of leprosy WBA that can be applied broadly in clinical or field settings.

* Corresponding author. Mailing address: Infectious Disease Research Institute, 1124 Columbia St., Suite 400, Seattle, WA 98104. Phone: (206) 330-2517. Fax: (206) 381-3678. E-mail: mduthie{at}idri.org

{triangledown} Published ahead of print on 10 September 2008.

Clinical and Vaccine Immunology, November 2008, p. 1659-1665, Vol. 15, No. 11
1071-412X/08/$08.00+0     doi:10.1128/CVI.00234-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Raman, V. S., O'Donnell, J., Bailor, H. R., Goto, W., Lahiri, R., Gillis, T. P., Reed, S. G., Duthie, M. S. (2009). Vaccination with the ML0276 Antigen Reduces Local Inflammation but Not Bacterial Burden during Experimental Mycobacterium leprae Infection. Infect. Immun. 77: 5623-5630 [Abstract] [Full Text]  


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