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 Connell, T. G.
Right arrow Articles by Wilkinson, K. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Connell, T. G.
Right arrow Articles by Wilkinson, K. A.

 Previous Article  |  Next Article 

Clinical and Vaccine Immunology, July 2007, p. 847-854, Vol. 14, No. 7
1071-412X/07/$08.00+0     doi:10.1128/CVI.00041-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Enhanced Ex Vivo Stimulation of Mycobacterium tuberculosis-Specific T Cells in Human Immunodeficiency Virus-Infected Persons via Antigen Delivery by the Bordetella pertussis Adenylate Cyclase Vector{triangledown}

Tom G. Connell ,1,2,{dagger},{ddagger} Muki S. Shey,1,{dagger} Ronnett Seldon,1,{ddagger} Molebogeng X. Rangaka,1,{ddagger} Gilles van Cutsem,3,{ddagger} Marcela Simsova,4,{ddagger} Zuzana Marcekova,4 Peter Sebo,4 Nigel Curtis,2,{ddagger} Lavanya Diwakar,1,{ddagger} Graeme A. Meintjes,1,{ddagger} Claude Leclerc,5 Robert J. Wilkinson,1,6,{ddagger} and Katalin A. Wilkinson1,6,{ddagger}*

Institute of Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Observatory 7925, South Africa,1 Department of Paediatrics, University of Melbourne, Infectious Diseases Unit, Department of General Medicine, and Murdoch Children's Research Institute, Royal Children's Hospital Melbourne, Parkville, Victoria, Australia,2 Médecins Sans Frontières, Khayelitsha site B, South Africa,3 Institute of Microbiology, Czech Academy of Sciences, Prague, Czech Republic,4 Unite de Régulation Immunitaires et Vaccinologie, Inserm E352, Institut Pasteur, Paris, France,5 Wellcome Trust Center for Research in Clinical Tropical Medicine, Division of Medicine, Imperial College London, London, United Kingdom6

Received 24 December 2006/ Returned for modification 27 March 2007/ Accepted 8 May 2007

The genetically detoxified Bordetella pertussis adenylate cyclase is a promising delivery system for immunodominant tuberculosis antigens in gamma interferon release assays. This system has not been evaluated in human immunodeficiency virus (HIV)-infected persons in high tuberculosis prevalence areas. A whole-blood gamma interferon release assay with Mycobacterium tuberculosis antigens (early-secreted antigenic target 6, culture filtrate protein 10, alpha-crystallin 2, and TB10.3) delivered by adenylate cyclase in addition to native tuberculosis antigens (without adenylate cyclase delivery) was evaluated in 119 adults in Khayelitsha Township, Cape Town, South Africa. Results were compared to tuberculin skin test results of 41 HIV-positive and 42 HIV-negative asymptomatic persons, in addition to 36 HIV-positive persons with recently diagnosed smear- or culture-positive pulmonary tuberculosis. Delivery of tuberculosis antigens by adenylate cyclase decreased by 10-fold the amount of antigen required to restimulate T cells. Furthermore, the responses of HIV-positive persons with a low response to native tuberculosis antigens were enhanced when these antigens were delivered by adenylate cyclase. When gamma interferon responses to the tuberculosis antigens (with or without delivery by adenylate cyclase) were combined, a significantly higher number of patients were scored positive than by tuberculin skin testing. Ex vivo responses to tuberculosis antigens delivered by adenylate cyclase are maintained in the context of HIV infection. Our findings suggest that the majority of those in this population are infected with tuberculosis, which is of significant public health importance.

* Corresponding author. Mailing address: Room S2.16, Institute of Infectious Diseases and Molecular Medicine, Wernher & Beit Building South, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory 7925, South Africa. Phone: 27 21 406 6793. Fax: 27 21 406 6796. E-mail: katalin.wilkinson{at}imperial.ac.uk

{triangledown} Published ahead of print on 23 May 2007.

{dagger} T.G.C. and M.S.S. are joint first authors.

{ddagger} This study was designed by K.A.W., M.X.R., L.D., and R.J.W., with a substantial contribution to conception by G.V.C., M.X.R., G.V.C., L.D., and G.A.M. were responsible for counseling, recruiting, and treating the patients involved. M.S., T.G.C., R.S., L.D., and K.A.W. performed and interpreted the IFNGRAs. T.G.C., K.A.W., R.J.W., and N.C. prepared a draft manuscript that was subsequently approved by all of us.

Clinical and Vaccine Immunology, July 2007, p. 847-854, Vol. 14, No. 7
1071-412X/07/$08.00+0     doi:10.1128/CVI.00041-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Meintjes, G., Wilkinson, K. A., Rangaka, M. X., Skolimowska, K., van Veen, K., Abrahams, M., Seldon, R., Pepper, D. J., Rebe, K., Mouton, P., van Cutsem, G., Nicol, M. P., Maartens, G., Wilkinson, R. J. (2008). Type 1 Helper T Cells and FoxP3-positive T Cells in HIV-Tuberculosis-associated Immune Reconstitution Inflammatory Syndrome. Am. J. Respir. Crit. Care Med. 178: 1083-1089 [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»