title: Immunogenicity of Mycobacterium leprae unique antigens in leprosy endemic populations in Asia and Africa.
abstract: Ongoing transmission of leprosy is evident from the stable disease incidence in high burden areas. Tools for early detection of Mycobacterium leprae (M. leprae) infection, particularly in sub-clinically infected individuals, are urgently required to reduce transmission. Following the sequencing of the M. leprae genome, many M. leprae-unique candidate proteins have been identified, several of which have been tested for induction of M. leprae specific T cell responses in different leprosy endemic areas. In this study, 21 M. leprae-unique proteins and 10 peptide pools covering the complete sequence of five M. leprae-unique proteins (ML0576, ML1989, ML1990, ML2283, and ML2567) were evaluated in 160 individuals in Nepal and Ethiopia. These included: tuberculoid and borderline tuberculoid (TT/BT), borderline borderline and borderline lepromatous (BB/BL) leprosy patients; healthy household contacts (HHC); tuberculosis (TB) patients and endemic controls (EC). Immunogenicity of the proteins was determined by IFN-gamma secretion via stimulation of PBMC in 6 days lymphocyte stimulation tests (LST) or in whole blood assays (WBA). In LST, BB/BL patients (40%) responded to ML0573 and ML1601 whereas ML1604 was most immunogenic in TT/BT (35%) and HHC (36%). Additionally, significant numbers of EC displayed IFN-gamma production in response to ML0573 (54%), ML1601 (50%) and ML1604 (54%). TB patients on the other hand, hardly responded to any of the proteins except for ML1989. Comparison of IFN-gamma responses to ML0121, ML0141 and ML0188 for TT/BT patients showed specific increase in diluted 6 days WBA compared to the undiluted 24 hours WBA, whereas EC showed a reduced response in the diluted WBA, which may indicate detection of disease-specific responses in the 6 days WBA. In summary, identification of multiple M. leprae proteins inducing M. leprae-specific T cell responses in groups at high risk of developing leprosy may contribute to improve early detection for M. leprae infection.
authors.affiliation: Department of Infectious Diseases, Leiden University Medical Center, The Netherlands.
authors.forename: Kidist
authors.initials: K
authors.lastname: Bobosha
authors.forename: Jolien J
authors.initials: JJ
authors.lastname: Van Der Ploeg-Van Schip
authors.forename: Martha
authors.initials: M
authors.lastname: Zewdie
authors.forename: Bishwa Raj
authors.initials: BR
authors.lastname: Sapkota
authors.forename: Deanna A
authors.initials: DA
authors.lastname: Hagge
authors.forename: Kees L M C
authors.initials: KL
authors.lastname: Franken
authors.forename: Wondmagegn
authors.initials: W
authors.lastname: Inbiale
authors.forename: Abraham
authors.initials: A
authors.lastname: Aseffa
authors.forename: Tom H M
authors.initials: TH
authors.lastname: Ottenhoff
authors.forename: Annemieke
authors.initials: A
authors.lastname: Geluk
mesh_terms: D000328:Adult; D000349:Africa / Q000453:epidemiology; D000942:Antigens, Bacterial / Q000276:immunology*; D001208:Asia / Q000453:epidemiology; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology; D019353:Endemic Diseases; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D007918:Leprosy / Q000175:diagnosis / Q000453:epidemiology / Q000276:immunology* / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D009166:Mycobacterium leprae / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D007371:Interferon-gamma