This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ewer, K. Articles by Vordermeier, M. Search for Related Content PubMed PubMed Citation Articles by Ewer, K. Articles by Vordermeier, M.

 Previous Article  |  Next Article 

Clinical and Vaccine Immunology, January 2006, p. 90-97, Vol. 13, No. 1
1071-412X/06/$08.00+0     doi:10.1128/CVI.13.1.90-97.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Antigen Mining with Iterative Genome Screens Identifies Novel Diagnostics for the Mycobacterium tuberculosis Complex

Katie Ewer,^1,* Paul Cockle,^1, Steve Gordon,¹ Huma Mansoor,¹ Marc Govaerts,² Karl Walravens,² Sylvie Marché,² Glyn Hewinson,¹ and Martin Vordermeier¹

TB Research Group, Veterinary Laboratories Agency—Weybridge, New Haw, Addlestone, Surrey, KT15 3NB, United Kingdom,¹ Veterinary and Agrochemical Research Center, Groeselenberg 99, B-1180 Brussels, Belgium²

Received 29 September 2005/ Returned for modification 17 October 2005/ Accepted 9 November 2005

The definition of antigens for the diagnosis of human and bovine tuberculosis is a research priority. If diagnosis is to be used alongside Mycobacterium bovis BCG-based vaccination regimens, it will be necessary to have reagents that allow the discrimination of infected and vaccinated animals. A list of 42 potential M. bovis-specific antigens was prepared by comparative analysis of the genomes of M. bovis, M. avium subsp. avium, M. avium subsp. paratuberculosis, and Streptomyces coelicolor. Potential antigens were tested by applying them in a high-throughput peptide-based screening system to M. bovis-infected and BCG-vaccinated cattle and to cattle without prior exposure to M. bovis. A response hierarchy of antigens was established by comparing responses in infected animals. Three antigens (Mb2555, Mb2890, and Mb3895) were selected for further study, as they were strongly recognized in experimentally infected animals but with low or no frequency in BCG-vaccinated and naïve cows. Interestingly, all three antigens were recognized in animals vaccinated against Johne's disease, suggesting the presences of epitopes cross-reacting with M. avium subsp. paratuberculosis antigens. Eight peptides from the three antigens studied in detail were identified as immunodominant and were characterized in terms of major histocompatibility complex class II restriction element usage and shown to be restricted through both DR and DQ molecules. Reasons for antigenic cross-reactivity with M. avium subsp. paratuberculosis and refinement of the in silico strategy to predict such cross-reactivity from the primary protein sequence will be discussed. Evaluation of the peptides identified from the three dominant antigens by use of larger field studies is now a priority.

K.E. and P.C. contributed equally to this study.

This article has been cited by other articles:

• Sidders, B., Pirson, C., Hogarth, P. J., Hewinson, R. G., Stoker, N. G., Vordermeier, H. M., Ewer, K. (2008). Screening of Highly Expressed Mycobacterial Genes Identifies Rv3615c as a Useful Differential Diagnostic Antigen for the Mycobacterium tuberculosis Complex. Infect. Immun. 76: 3932-3939 [Abstract] [Full Text]  
• Vordermeier, H. M., Brown, J., Cockle, P. J., Franken, W. P. J., Arend, S. M., Ottenhoff, T. H. M., Jahans, K., Hewinson, R. G. (2007). Assessment of Cross-Reactivity between Mycobacterium bovis and M. kansasii ESAT-6 and CFP-10 at the T-Cell Epitope Level. CVI 14: 1203-1209 [Abstract] [Full Text]  
• Sharma, A., Saha, A., Bhattacharjee, S., Majumdar, S., Das Gupta, S. K. (2006). Specific and Randomly Derived Immunoactive Peptide Mimotopes of Mycobacterial Antigens. CVI 13: 1143-1154 [Abstract] [Full Text]  
• Mustafa, A. S., Skeiky, Y. A., Al-Attiyah, R., Alderson, M. R., Hewinson, R. G., Vordermeier, H. M. (2006). Immunogenicity of Mycobacterium tuberculosis Antigens in Mycobacterium bovis BCG-Vaccinated and M. bovis-Infected Cattle.. Infect. Immun. 74: 4566-4572 [Abstract] [Full Text]