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Bioinformatics analysis of Mycobacterium tuberculosis‐specific genomic regions to identify immunodominant proteins and peptides
Author(s) -
Mustafa AbuSalim
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.52.2
Subject(s) - immunogenicity , antigen , epitope , immune system , mycobacterium tuberculosis , biology , in silico , tuberculosis , peripheral blood mononuclear cell , tuberculosis vaccines , virology , human leukocyte antigen , immunology , gene , in vitro , medicine , genetics , pathology
This study was aimed to identify immunodominant proteins and peptides encoded by Mycobacterium tuberculosis‐specific genomic regions of differences (RDs) by using bioinformatics to predict for HLA‐DR binding regions. The analysis of RD proteins and peptides by in silico methods (using computational programs to predict major and HLA‐promiscuous antigenic proteins and peptides) and wet‐lab experiments (using peripheral blood mononuclear cells and sera from TB patients and BCG‐vaccinated healthy subjects to asses antigen‐specific cellular and humoral immune responses in vitro) identified several major antigens and peptides. To evaluate them for in vivo reactivity, the genes of immunodominant antigens were cloned and expressed in DNA vaccine vectors (pUMVC6 and pUMVC7) and mycobacterial hosts, i.e. BCG, M. vaccae and M. smegmatis. Immunizations of mice and guinea‐pigs with the recombinant constructs induced antigen‐specific cellular and humoral immune responses in these animal models of TB. Each of these proteins had several T and B cell epitopes scattered throughout the sequences, which confirmed their strong immunogenicity and appropriateness for diagnostic and vaccine applications. Supported by Kuwait University Research Administration grants MI01/10 and GM01/01.