1. Mycobacterium leprae Recombinant Antigen Induces High Expression of Multifunction T Lymphocytes and Is Promising as a Specific Vaccine for Leprosy.
- Author
-
Bezerra-Santos M, do Vale-Simon M, Barreto AS, Cazzaniga RA, de Oliveira DT, Barrios MR, Ferreira AR, Santos-Bio NC, Reed SG, de Almeida RP, Corrêa CB, Duthie MS, and de Jesus AR
- Subjects
- Adult, Aged, Antigens, Bacterial genetics, CD4-Positive T-Lymphocytes metabolism, CD4-Positive T-Lymphocytes microbiology, Female, Humans, Interferon-gamma immunology, Interferon-gamma metabolism, Interleukin-2 immunology, Interleukin-2 metabolism, Leprosy, Multibacillary microbiology, Leprosy, Multibacillary prevention & control, Leprosy, Paucibacillary microbiology, Leprosy, Paucibacillary prevention & control, Male, Middle Aged, Mycobacterium leprae physiology, Recombinant Proteins immunology, Th1 Cells immunology, Th1 Cells metabolism, Vaccines therapeutic use, Young Adult, Antigens, Bacterial immunology, CD4-Positive T-Lymphocytes immunology, Leprosy, Multibacillary immunology, Leprosy, Paucibacillary immunology, Mycobacterium leprae immunology, Vaccines immunology
- Abstract
Leprosy is a chronic disease caused by M. leprae infection that can cause severe neurological complications and physical disabilities. A leprosy-specific vaccine would be an important component within control programs but is still lacking. Given that multifunctional CD4 T cells [i.e., those capable of simultaneously secreting combinations of interferon (IFN)-γ, interleukin (IL)-2, and tumor necrosis factor (TNF)] have now been implicated in the protective response to several infections, we tested the hypothesis if a recombinant M. leprae antigen-specific multifunctional T cells differed between leprosy patients and their healthy contacts. We used whole blood assays and peripheral blood mononuclear cells to characterize the antigen-specific T cell responses of 39 paucibacillary (PB) and 17 multibacillary (MB) leprosy patients and 31 healthy household contacts (HHC). Cells were incubated with either crude mycobacterial extracts ( M. leprae cell sonicate-MLCS) and purified protein derivative (PPD) or recombinant ML2028 protein, the homolog of M. tuberculosis Ag85B. Multiplex assay revealed antigen-specific production of IFN-γ and IL-2 from cells of HHC and PB, confirming a Th1 bias within these individuals. Multiparameter flow cytometry then revealed that the population of multifunctional ML2028-specific T cells observed in HHC was larger than that observed in PB patients. Taken together, our data suggest that these multifunctional antigen-specific T cells provide a more effective response against M. leprae infection that prevents the development of leprosy. These data further our understanding of M. leprae infection/leprosy and are instructive for vaccine development.
- Published
- 2018
- Full Text
- View/download PDF