TY - JOUR T1 - In silico epitope analysis of unique and membrane associated proteins from Mycobacterium avium subsp. paratuberculosis for immunogenicity and vaccine evaluation. JF - J Theor Biol Y1 - 2015 A1 - Carlos Perla A1 - Virginie Roupie A1 - Holbert, Sébastien A1 - Ascencio, Felipe A1 - Huygen, Kris A1 - Gomez-Anduro, Gracia A1 - Branger, Maxime A1 - Reyes-Becerril, Martha A1 - Angulo, Carlos KW - Animals KW - Antigens, Bacterial KW - Bacterial Vaccines KW - Cattle KW - Computer Simulation KW - Epitopes, B-Lymphocyte KW - Epitopes, T-Lymphocyte KW - HLA-DR Antigens KW - Humans KW - Interferon-gamma KW - Membrane Proteins KW - Models, Immunological KW - Mycobacterium avium subsp. paratuberculosis AB -

Mycobacterium avium subsp. paratuberculosis (MAP) is the etiologic agent of paratuberculosis disease affecting ruminants worldwide. The aim of this study was to identify potential candidate antigens and epitopes by bio and immuno-informatic tools which could be later evaluated as vaccines and/or diagnosis. 110 protein sequences were selected from MAP K-10 genome database: 48 classified as putative enzymes involved in surface polysaccharide and lipopolysaccharide synthesis, as membrane associated and secreted proteins, 32 as conserved membrane proteins, and 30 as absent from other mycobacterial genomes. These 110 proteins were preliminary screened for Major Histocompatibility Complex (MHC) class II affinity and promiscuity using ProPred program. In addition, subcellular localization and host protein homology was analyzed. From these analyses, 23 MAP proteins were selected for a more accurate inmunoinformatic analysis (i.e. T cell and B cell epitopes analysis) and for homology with mycobacterial proteins. Finally, eleven MAP proteins were identified as potential candidates for further immunogenic evaluation: six proteins (MAP0228c, MAP1239c, MAP2232, MAP3080, MAP3131 and MAP3890) were identified as presenting potential T cell epitopes, while 5 selected proteins (MAP0232c, MAP1240c, MAP1738, MAP2239 and MAP3641c) harbored a large numbers of epitopes predicted to induce both cell- and antibody-mediated immune responses. Moreover, immunogenicity of selected epitopes from MAP1239c were evaluated in IFN-γ release assay. In summary, eleven M. avium subsp. paratuberculosis proteins were identified by in silico analysis and need to be further evaluated for their immunodiagnostic and vaccine potential in field and mice model.

VL - 384 U1 - http://www.ncbi.nlm.nih.gov/pubmed/26279134?dopt=Abstract M3 - 10.1016/j.jtbi.2015.08.003 ER -