In silico predicted mycobacterial epitope elicits in vitro T-cell responses

• DOI: 10.1016/j.molimm.2014.04.009
• Publication Date: 2014-05-20T05:45:08Z
• Authors: Md Kawsar Khan; Shabnam Zaman; Sajib Chakraborty; Rajib Chakravorty; Mohammad Murshid ...; Taufiqur Rahman B...; Muhammad Jubayer ...; Carmen Fernández; Firdausi Qadri; Zeba I. Seraj
• Keywords: CD4-Positive T-Lymphocytes; 0301 basic medicine; T-Lymphocytes; Molecular Sequence Data; Antigens, Bacterial/genetics; Epitopes, T-Lymphocyte; CD8-Positive T-Lymphocytes; Cross Reactions; CD8-Positive T-Lymphocytes/immunology; 03 medical and health sciences; Bacterial Proteins; HLA Antigens; Humans; Computer Simulation; Amino Acid Sequence; Tuberculosis Vaccines; Cell Proliferation; Acyltransferases/genetics; Antigens, Bacterial; Protein Binding/immunology; Bacterial Proteins/genetics; Mycobacterium tuberculosis; T-Lymphocytes/immunology; Tuberculosis Vaccines/immunology; 3. Good health; epitope mapping; cell proliferation; Mycobacterium tuberculosis/genetics; Epitopes, T-Lymphocyte/genetics; CD4-Positive T-Lymphocytes/immunology; Leukocyte Common Antigens; HLA Antigens/immunology; Cross Reactions/immunology; Acyltransferases; Epitope Mapping; Leukocyte Common Antigens/immunology; Protein Binding

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.