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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2018.02920

Mycobacterium leprae recombinant antigen induces high expression of multifunction T lymphocytes and is promising as a specific vaccine for leprosy

 Márcio B. Santos1*, Marise d. Simon1,  Aline S. Barreto1,  Rodrigo A. Cazzaniga1, Daniela T. de Oliveira1, 2,  Mônica R. Barrios1, Alex R. Ferreira3, Nanci C. Santos-Bio3, Steven G. Reed4, Roque P. Almeida1, 3, 5,  Cristiane B. Correa1, Malcolm S. Duthie4 and  Amélia R. De Jesus1, 3, 5
  • 1Laboratory of Immunology and Molecular Biology, Federal University of Sergipe, Brazil
  • 2Departament of Health Education, Federal University of Sergipe, Brazil
  • 3Departamento de Medicina, Universidade Federal de Sergipe, Brazil
  • 4Infectious Disease Research Institute, United States
  • 5Instituto de Investigação em Imunologia, Instituto Nacional de Ciência e Tecnologia (iii-INCT), Brazil

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)-, 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- 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.

Keywords: Leprosy, ML2028, multifunctional T cells, Immunopathogenesis, Mycobacterium leprae

Received: 10 Aug 2018; Accepted: 28 Nov 2018.

Edited by:

Jeffrey K. Actor, University of Texas Health Science Center at Houston, United States

Reviewed by:

Juraj Ivanyi, King's College London, United Kingdom
John S. Spencer, Colorado State University, United States  

Copyright: © 2018 Santos, Simon, Barreto, Cazzaniga, de Oliveira, Barrios, Ferreira, Santos-Bio, Reed, Almeida, Correa, Duthie and De Jesus. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: MD, PhD. Márcio B. Santos, Federal University of Sergipe, Laboratory of Immunology and Molecular Biology, São Cristóvão, Brazil, bio_marcio2006@hotmail.com