In silico predicted mycobacterial epitope elicits in vitro T-cell responses.
Epitope-based vaccines permit the selection of only a specific subset of epitopes to induce the necessary immune response, thus providing a rational alternative to conventional design approaches. Using a range of immunoinformatics tools, we identified a novel, contiguous 28 amino acid multi-epitope cluster within the highly conserved secretory protein Ag85B of Mycobacterium tuberculosis, the causative agent of TB. This cluster, named Ep85B, is composed of epitopes which bind to three HLA Class I and 15 Class II molecules, and harbors the potential to generate 99% population coverage in TB-endemic regions. We experimentally evaluated the capacity of Ep85B to elicit T-cell immune responses using whole blood cells and, as predicted, observed significant increases in populations of both CD4+ and memory CD4+ CD45RO+ T-cells. Our results demonstrate the practical utility of an epitope-based design methodology - a strategy that, following further evaluation, may serve as an additional tool for the development of novel vaccine candidates against TB and other diseases.
Centre for Vaccine Sciences, International Centre for Diarrhoeal Diseases Research, Bangladesh (icddr,b), Dhaka, Bangladesh; Department of Biochemistry and Molecular Biology, University of Dhaka, Bangladesh.
Md Kawsar
MK
Khan
Centre for Vaccine Sciences, International Centre for Diarrhoeal Diseases Research, Bangladesh (icddr,b), Dhaka, Bangladesh; Department of Biochemistry and Molecular Biology, University of Dhaka, Bangladesh.
Shabnam
S
Zaman
Department of Biochemistry and Molecular Biology, University of Dhaka, Bangladesh.
Sajib
S
Chakraborty
Victoria Research Laboratory, National ICT Australia, Australia.
Rajib
R
Chakravorty
Centre for Vaccine Sciences, International Centre for Diarrhoeal Diseases Research, Bangladesh (icddr,b), Dhaka, Bangladesh.
Mohammad Murshid
MM
Alam
Centre for Vaccine Sciences, International Centre for Diarrhoeal Diseases Research, Bangladesh (icddr,b), Dhaka, Bangladesh.
Taufiqur Rahman
TR
Bhuiyan
Department of Molecular Biosciences, The Wenner-Gren Institute (MBW), The Arrhenius Laboratories, Stockholm University, Sweden.
Muhammad Jubayer
MJ
Rahman
Department of Molecular Biosciences, The Wenner-Gren Institute (MBW), The Arrhenius Laboratories, Stockholm University, Sweden.
Carmen
C
Fernández
Centre for Vaccine Sciences, International Centre for Diarrhoeal Diseases Research, Bangladesh (icddr,b), Dhaka, Bangladesh.
Firdausi
F
Qadri
Department of Biochemistry and Molecular Biology, University of Dhaka, Bangladesh. Electronic address: zebai@univdhaka.edu.
Zeba I
ZI
Seraj
D000217:Acyltransferases / Q000235:genetics / Q000276:immunology*; D000595:Amino Acid Sequence; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation; D003198:Computer Simulation; D003429:Cross Reactions / Q000276:immunology; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology / Q000378:metabolism; D006801:Humans; D017493:Leukocyte Common Antigens / Q000276:immunology / Q000378:metabolism; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D032581:Tuberculosis Vaccines / Q000276:immunology
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D018984:Epitopes, T-Lymphocyte; D006680:HLA Antigens; D032581:Tuberculosis Vaccines; D000217:Acyltransferases; C121433:antigen 85B, Mycobacterium tuberculosis; D017493:Leukocyte Common Antigens
Ag85B; Epitope vaccine; Immunoinformatics; Tuberculosis