Identification of antigens specific to non-tuberculous mycobacteria: the Mce family of proteins as a target of T cell immune responses

• Published in: PloS one 2011-10, Vol.6 (10), p.e26434-e26434
• Main Authors: Checkley, Anna M, Wyllie, David H, Scriba, Thomas J, Golubchik, Tanya, Hill, Adrian V S, Hanekom, Willem A, McShane, Helen
• Format: Article
• Language: English
• Subjects: Amino acid sequence; Antigens; Antigens, Bacterial - isolation & purification; Bacillus Calmette-Guerin vaccine; Bacterial Proteins - administration & dosage; Bacterial Proteins - immunology; Bacterial Vaccines - immunology; BCG; BCG Vaccine - immunology; Biology; Cells (Biology); Clinical trials; Clusters; Computational Biology; Cytokines; Diagnostic systems; Drug resistance; Enzyme-linked immunosorbent assay; Exposure; Genomes; Genomics; Humans; Immune response; Immune response (cell-mediated); Immune system; Infections; Infectious diseases; Leprosy; Low level; Lymphocytes; Lymphocytes T; Medical research; Medicine; Mycobacterium - immunology; Mycobacterium bovis; Mycobacterium tuberculosis; Mycobacterium ulcerans; Pandemics; Proteins; South Africa; T cells; T-Lymphocytes - immunology; Teenagers; Tuberculosis; Tuberculosis vaccines; Tuberculosis Vaccines - immunology; United Kingdom; United States; Vaccines
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0026434

The lack of an effective TB vaccine hinders current efforts in combating the TB pandemic. One theory as to why BCG is less protective in tropical countries is that exposure to non-tuberculous mycobacteria (NTM) reduces BCG efficacy. There are currently several new TB vaccines in clinical trials, and NTM exposure may also be relevant in this context. NTM exposure cannot be accurately evaluated in the absence of specific antigens; those which are known to be present in NTM and absent from M. tuberculosis and BCG. We therefore used a bioinformatic pipeline to define proteins which are present in common NTM and absent from the M. tuberculosis complex, using protein BLAST, TBLASTN and a short sequence protein BLAST to ensure the specificity of this process. We then assessed immune responses to these proteins, in healthy South Africans and in patients from the United Kingdom and United States with documented exposure to NTM. Low level responses were detected to a cluster of proteins from the mammalian cell entry family, and to a cluster of hypothetical proteins, using ex vivo ELISpot and a 6 day proliferation assay. These early findings may provide a basis for characterising exposure to NTM at a population level, which has applications in the field of TB vaccine design as well as in the development of diagnostic tests.