02408nas a2200277 4500000000100000008004100001100002100042700001700063700001500080700001700095700001600112700001500128700001600143700001700159700001100176700001800187700001500205700001300220700001300233245013100246856008000377300000900457490000600466520164400472022001402116 2018 d1 aBezerra-Santos M1 aVale-Simon M1 aBarreto AS1 aCazzaniga RA1 aOliveira DT1 aBarrios MR1 aFerreira AR1 aSantos-Bio N1 aReed S1 aDe Almeida RP1 aCorrêa CB1 aDuthie M1 aJesus AR00aRecombinant antigen induces high expression of multifunction T lymphocytes and is promising as a specific vaccine for leprosy. uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6315144/pdf/fimmu-09-02920.pdf a29200 v93 a

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.

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