Mycobacterium leprae Recombinant Antigen Induces High Expression of Multifunction T Lymphocytes and Is Promising as a Specific Vaccine for Leprosy

• Published in: Frontiers in immunology Vol. 9; p. 2920
• Main Authors: Bezerra-Santos, Márcio, do Vale-Simon, Marise, Barreto, Aline Silva, Cazzaniga, Rodrigo Anselmo, de Oliveira, Daniela Teles, Barrios, Mônica Rueda, Ferreira, Alex Ricardo, Santos-Bio, Nanci C, Reed, Steven G, de Almeida, Roque Pacheco, Corrêa, Cristiane Bani, Duthie, Malcolm S, de Jesus, Amélia Ribeiro
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 12.12.2018
• Subjects: Adult; Aged; Antigens, Bacterial - genetics; Antigens, Bacterial - immunology; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD4-Positive T-Lymphocytes - microbiology; Female; Humans; Immunology; immunopathogenesis; Interferon-gamma - immunology; Interferon-gamma - metabolism; Interleukin-2 - immunology; Interleukin-2 - metabolism; leprosy; Leprosy, Multibacillary - immunology; Leprosy, Multibacillary - microbiology; Leprosy, Multibacillary - prevention & control; Leprosy, Paucibacillary - immunology; Leprosy, Paucibacillary - microbiology; Leprosy, Paucibacillary - prevention & control; Male; Middle Aged; ML2028; Multifunctional T cells; Mycobacterium leprae; Mycobacterium leprae - immunology; Mycobacterium leprae - physiology; Recombinant Proteins - immunology; Th1 Cells - immunology; Th1 Cells - metabolism; Vaccines - immunology; Vaccines - therapeutic use; Young Adult; leprosy; ML2028; Mycobacterium leprae; immunopathogenesis; Multifunctional T cells
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2018.02920

Leprosy is a chronic disease caused by 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 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 ( cell sonicate-MLCS) and purified protein derivative (PPD) or recombinant ML2028 protein, the homolog of 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 infection that prevents the development of leprosy. These data further our understanding of infection/leprosy and are instructive for vaccine development.