Towards an immunodiagnostic test for leprosy.
In addition to multidrug therapy, elimination of leprosy requires improved diagnostic methods. Using a comparative genomics approach, 17 potential protein antigens (MLP) that are restricted to Mycobacterium leprae, or of limited distribution, were produced and tested for antigen-specific immune responses on leprosy patients, healthy contacts of leprosy patients, and tuberculosis patients in Mali and Bangladesh, as well as on non-endemic controls. T-cell antigenicity of MLP was confirmed by IFN-gamma production in whole-blood assays with the highest responses observed in paucibacillary leprosy patients and healthy contacts. Four MLP behaved well in both countries and induced significantly different responses between the study groups. Peptides carrying T cell epitopes from one of the antigens gave promising results in restimulation assays in mice and immune responses were not influenced by prior exposure to BCG or environmental mycobacteria. This study provides the immunological framework for the development of a specific, peptide-based immunodiagnostic test for leprosy.
Aráoz
Romulo
R
Unité de Génétique Moléculaire Bactérienne, Institut Pasteur, 28 rue du Docteur Roux, 75724 Paris Cedex 15, France.
Honoré
Nadine
N
Banu
Sayera
S
Demangel
Caroline
C
Cissoko
Yakouba
Y
Arama
Charles
C
Uddin
Mohammad Khaja Mafij
MK
Hadi
S K Abdul
SK
Monot
Marc
M
Cho
Sang-Nae
SN
Ji
Baohong
B
Brennan
Patrick J
PJ
Sow
Samba
S
Cole
Stewart T
ST
D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D000942:Antigens, Bacterial / Q000276:immunology; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007159:Immunologic Tests / Q000379:methods*; D007371:Interferon-gamma / Q000096:biosynthesis; D007918:Leprosy / Q000175:diagnosis* / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009166:Mycobacterium leprae / Q000276:immunology* / Q000302:isolation & purification; D010455:Peptides / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D010455:Peptides; D007371:Interferon-gamma