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

 Previous Article  |  Next Article 

Infection and Immunity, December 2002, p. 6996-7003, Vol. 70, No. 12
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.12.6996-7003.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Identification of Novel Mycobacterium tuberculosis Antigens with Potential as Diagnostic Reagents or Subunit Vaccine Candidates by Comparative Genomics

P. J. Cockle,1 S. V. Gordon,1 A. Lalvani,2 B. M. Buddle,3 R. G. Hewinson,1 and H. M. Vordermeier1*

TB Research Group, Department of Bacterial Diseases, Veterinary Laboratories Agency—Weybridge, New Haw, Addlestone,1 Nuffield Department of Clinical Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom,2 AgResearch, Wallaceville Animal Research Centre, Upper Hutt, New Zealand3

Received 15 March 2002/ Returned for modification 3 June 2002/ Accepted 20 August 2002

An independent review for the British government has concluded that the development of a cattle vaccine against Mycobacterium bovis holds the best long-term prospects for tuberculosis control in British herds. The development of complementary diagnostic tests to differentiate between vaccinated and infected animals is necessary to allow the continuation of test-and-slaughter-based control policies alongside vaccination. Vaccination with M. bovis bacillus Calmette-Guérin (BCG), the only available vaccine, results in tuberculin purified protein derivative sensitivity and has shown varying vaccine efficacies in cattle. Thus, identification of more-specific reagents to distinguish between vaccination and infection, as well as the identification of subunit vaccine candidates for improved tuberculosis vaccines, is a research priority. In the present study, we applied comparative genomics to identify M. bovis-Mycobacterium tuberculosis antigens whose genes had been deleted in BCG Pasteur. In total, 13 open reading frames (ORFs) from the RD1, RD2, and RD14 regions of the M. tuberculosis genome were selected. Pools of overlapping peptides spanning these ORFs were tested in M. bovis-infected (n = 22), BCG-vaccinated (n = 6), and unvaccinated (n = 10) control cattle. All were recognized in infected cattle, with responder frequencies varying between 16 and 86%. In particular, eight highly immunogenic antigens were identified whose potentials as diagnostic reagents or as subunit vaccines warrant further study (Rv1983, Rv1986, Rv3872, Rv3873, Rv3878, Rv3879c, Rv1979c, and Rv1769).

* Corresponding author. Mailing address: TB Research Group, Department of Bacterial Diseases, Veterinary Laboratories Agency-Weybridge, New Haw, Addlestone, KT15 3NB, United Kingdom. Phone: 44 1932 357 884. Fax: 44 1932 357 684. E-mail: mvordermeier.vla{at}gtnet.gov.uk.

Editor: S. H. E. Kaufmann

Infection and Immunity, December 2002, p. 6996-7003, Vol. 70, No. 12
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.12.6996-7003.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Schiller, I., Vordermeier, H. M., Waters, W. R., Palmer, M., Thacker, T., Whelan, A., Hardegger, R., Marg-Haufe, B., Raeber, A., Oesch, B. (2009). Assessment of Mycobacterium tuberculosis OmpATb as a Novel Antigen for the Diagnosis of Bovine Tuberculosis. CVI 16: 1314-1321 [Abstract] [Full Text]  
  • Meikle, V., Alito, A., Llera, A. S., Gioffre, A., Peralta, A., Buddle, B. M., Cataldi, A. (2009). Identification of Novel Mycobacterium bovis Antigens by Dissection of Crude Protein Fractions. CVI 16: 1352-1359 [Abstract] [Full Text]  
  • 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]  
  • Golby, P., Nunez, J., Cockle, P. J., Ewer, K., Logan, K., Hogarth, P., Vordermeier, H. M., Hinds, J., Hewinson, R. G., Gordon, S. V. (2008). Characterization of two in vivo-expressed methyltransferases of the Mycobacterium tuberculosis complex: antigenicity and genetic regulation. Microbiology 154: 1059-1067 [Abstract] [Full Text]  
  • Aagaard, C., Govaerts, M., Meikle, V., Vallecillo, A. J., Gutierrez-Pabello, J. A., Suarez-Guemes, F., McNair, J., Cataldi, A., Espitia, C., Andersen, P., Pollock, J. M. (2006). Optimizing Antigen Cocktails for Detection of Mycobacterium bovis in Herds with Different Prevalences of Bovine Tuberculosis: ESAT6-CFP10 Mixture Shows Optimal Sensitivity and Specificity. J. Clin. Microbiol. 44: 4326-4335 [Abstract] [Full Text]  
  • Cockle, P. J., Gordon, S. V., Hewinson, R. G., Vordermeier, H. M. (2006). Field Evaluation of a Novel Differential Diagnostic Reagent for Detection of Mycobacterium bovis in Cattle. CVI 13: 1119-1124 [Abstract] [Full Text]  
  • Ameni, G., Aseffa, A., Engers, H., Young, D., Hewinson, G., Vordermeier, M. (2006). Cattle husbandry in ethiopia is a predominant factor affecting the pathology of bovine tuberculosis and gamma interferon responses to mycobacterial antigens.. CVI 13: 1030-1036 [Abstract] [Full Text]  
  • Leyten, E. M. S., Mulder, B., Prins, C., Weldingh, K., Andersen, P., Ottenhoff, T. H. M., van Dissel, J. T., Arend, S. M. (2006). Use of Enzyme-Linked Immunospot Assay with Mycobacterium tuberculosis- Specific Peptides for Diagnosis of Recent Infection with M. tuberculosis after Accidental Laboratory Exposure.. J. Clin. Microbiol. 44: 1197-1201 [Abstract] [Full Text]  
  • Ewer, K., Cockle, P., Gordon, S., Mansoor, H., Govaerts, M., Walravens, K., Marche, S., Hewinson, G., Vordermeier, M. (2006). Antigen Mining with Iterative Genome Screens Identifies Novel Diagnostics for the Mycobacterium tuberculosis Complex. CVI 13: 90-97 [Abstract] [Full Text]  
  • Parra, M., Cadieux, N., Pickett, T., Dheenadhayalan, V., Brennan, M. J. (2006). A PE Protein Expressed by Mycobacterium avium Is an Effective T-Cell Immunogen. Infect. Immun. 74: 786-789 [Abstract] [Full Text]  
  • Spencer, J. S., Dockrell, H. M., Kim, H. J., Marques, M. A. M., Williams, D. L., Martins, M. V. S. B., Martins, M. L. F., Lima, M. C. B. S., Sarno, E. N., Pereira, G. M. B., Matos, H., Fonseca, L. S., Sampaio, E. P., Ottenhoff, T. H. M., Geluk, A., Cho, S.-N., Stoker, N. G., Cole, S. T., Brennan, P. J., Pessolani, M. C. V. (2005). Identification of Specific Proteins and Peptides in Mycobacterium leprae Suitable for the Selective Diagnosis of Leprosy. J. Immunol. 175: 7930-7938 [Abstract] [Full Text]  
  • Purkayastha, A., Su, J., McGraw, J., Ditty, S. E., Hadfield, T. L., Seto, J., Russell, K. L., Tibbetts, C., Seto, D. (2005). Genomic and Bioinformatics Analyses of HAdV-4vac and HAdV-7vac, Two Human Adenovirus (HAdV) Strains That Constituted Original Prophylaxis against HAdV-Related Acute Respiratory Disease, a Reemerging Epidemic Disease. J. Clin. Microbiol. 43: 3083-3094 [Abstract] [Full Text]  
  • Wilkinson, K. A., Stewart, G. R., Newton, S. M., Vordermeier, H. M., Wain, J. R., Murphy, H. N., Horner, K., Young, D. B., Wilkinson, R. J. (2005). Infection Biology of a Novel {alpha}-Crystallin of Mycobacterium tuberculosis: Acr2. J. Immunol. 174: 4237-4243 [Abstract] [Full Text]  
  • Brock, I., Weldingh, K., Leyten, E. M. S., Arend, S. M., Ravn, P., Andersen, P. (2004). Specific T-Cell Epitopes for Immunoassay-Based Diagnosis of Mycobacterium tuberculosis Infection. J. Clin. Microbiol. 42: 2379-2387 [Abstract] [Full Text]  
  • Liu, X.-Q., Dosanjh, D., Varia, H., Ewer, K., Cockle, P., Pasvol, G., Lalvani, A. (2004). Evaluation of T-Cell Responses to Novel RD1- and RD2-Encoded Mycobacterium tuberculosis Gene Products for Specific Detection of Human Tuberculosis Infection. Infect. Immun. 72: 2574-2581 [Abstract] [Full Text]  
  • Demangel, C., Brodin, P., Cockle, P. J., Brosch, R., Majlessi, L., Leclerc, C., Cole, S. T. (2004). Cell Envelope Protein PPE68 Contributes to Mycobacterium tuberculosis RD1 Immunogenicity Independently of a 10-Kilodalton Culture Filtrate Protein and ESAT-6. Infect. Immun. 72: 2170-2176 [Abstract] [Full Text]  
  • Whelan, A. O., Hope, J. C., Howard, C. J., Clifford, D., Hewinson, R. G., Vordermeier, H. M. (2003). Modulation of the Bovine Delayed-Type Hypersensitivity Responses to Defined Mycobacterial Antigens by a Synthetic Bacterial Lipopeptide. Infect. Immun. 71: 6420-6420 [Abstract] [Full Text]  
  • Aagaard, C., Govaerts, M., Meng Okkels, L., Andersen, P., Pollock, J. M. (2003). Genomic Approach to Identification of Mycobacterium bovis Diagnostic Antigens in Cattle. J. Clin. Microbiol. 41: 3719-3728 [Abstract] [Full Text]  
  • Vordermeier, M., Whelan, A. O., Hewinson, R. G. (2003). Recognition of Mycobacterial Epitopes by T Cells across Mammalian Species and Use of a Program That Predicts Human HLA-DR Binding Peptides To Predict Bovine Epitopes. Infect. Immun. 71: 1980-1987 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»