Immunologically reactive M. leprae antigens with relevance to diagnosis and vaccine development

Abstract

BackgroundLeprosy is a chronic infectious disease caused by Mycobacterium leprae that can manifest a wide variety of immunological and clinical outcomes ranging from potent humoral responses among borderline lepromatous (BL) and lepromatous (LL) patients to strong cellular responses among tuberculoid (TT) and borderline tuberculoid (BT) patients. Until recently, relatively little has been known about the immune responses to individual proteins of M. leprae recognized during leprosy.MethodsThe immune reactivity to a panel of 33 M. leprae recombinant proteins was evaluated among leprosy patients and controls from a high endemic area for leprosy (Goiania/GO, Central Brazil). Serum IgG responses were measured by ELISA (45 participants/group) and T cell responses (20 participants/group) were evaluated by IFN-gamma production in 24 hours whole blood cultures with antigen (whole blood assay-WBA). Study groups were newly diagnosed, untreated TT/BT and BL/LL leprosy patients classified by Ridley Jopling criteria and household contacts of BL/LL patients (HHC). Control groups were HIV-1 negative pulmonary tuberculosis patients (TB) and healthy individuals from the same endemic area (EC). In silico predictions indicated the level of identity of M. leprae proteins with homologues in other mycobacteria and the presence of T cell and B cell epitopes.ResultsDespite the prediction that all proteins would be reactive, 16 of 33 (48%) of the single proteins tested were immunogenic (recognized in WBA or ELISA) and seventeen were non-immunogenic (not recognized in either assay). Among the 16 immunogenic proteins, 9 were considered leprosy specific in WBA inducing cell-mediated IFN-gamma secretion from TT/BT patients and HHC. Three of these proteins were also leprosy specific in serology being recognized by serum IgG from LL/BL patients. Seven of the immunogenic proteins were not leprosy specific.ConclusionsNew M. leprae antigens recognized by antibody responses of BL/LL patients and cellular responses of TT/BT leprosy patients were identified. An improved serological diagnostic test for leprosy could be developed by incorporating these IgG-reactive antigens to the current PGL-I based tests. Moreover our data indicate that the WBA is a robust, relatively simple and user friendly format for a T cell based diagnostic test. The field use of these test formats in leprosy endemic countries could contribute to early leprosy diagnosis before the development of deformities and disabilities.

Mycobacterium leprae virulence-associated peptides are indicators of exposure to M. leprae in Brazil, Ethiopia and Nepal

“…Moreover, these two peptides induced significant levels of IFN-γ and IP-10 in the Ethiopian EC high group, suggesting that the ML2055 p35 and ML2055 p42 peptides can detect M. leprae exposure in populations with diverse HLA-alleles. ML2055 has also been reported to induce strong serological responses in lepromatous patients (Sampaio et al 2011). The low response against ML2055 in the Ethiopian HHC group compared with the EC group could have been a result of an overexposure to mycobacteria.…”

A S52P mutation in the ‘α‐crystallin domain’ of Mycobacterium leprae HSP18 reduces its oligomeric size and chaperone function

“…Many antigens have crucial implications in the immune response of M. leprae pathogen [32][33][34]. Several of these antigens, with molecular weights in the range 10-70 kDa, belong to the HSP family [35].…”

Identification of serological biomarkers of infection, disease progression and treatment efficacy for leprosy

“…The best protein candidates to assess the IgG response include ML0405, ML2331, ML2055 (Reece et al 2006, Duthie et al 2007), ML2028 (Launois et al 1994) and ML2038 , Kai et al 2008. A bioinformatics analysis predicted ML0405 to be one of the most promiscuous M. leprae proteins studied to date and to contain T cell epitopes predicted to be recognised by 50 out of 51 human leukocyte antigen-DR alleles along with seven potential T cell epitopes and 39 potential B cell epitopes, whereas ML2331 contained 24 potential B cell epitopes (Sampaio et al 2011). The engineering of these two proteins into the fusion protein LID-1 has been shown to be effective in detecting antibody responses in virtually all MB patients, with specificity and sensitivity of 87% (Duthie et al 2007).…”