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Clin. Vaccine Immunol. doi:10.1128/CVI.00041-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Enhanced Ex vivo stimulation of Mycobacterium tuberculosis-specific T cells in HIV-infected persons via antigen delivery by the Bordetella pertussis adenylate cyclase vector

Institute of Infectious Diseases and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, South Africa; Dept of Paediatrics, University of Melbourne; Infectious Diseases Unit, Dept of General Medicine; & Murdoch Children's Research Institute, Royal Children's Hospital Melbourne, Australia; Médecins Sans Frontières, Khayelitsha site B, South Africa; Institute of Microbiology, Czech Academy of Sciences, Prague, Czech Republic; Unite de Régulation Immunitaires et Vaccinologie, Inserm, E352, Institut Pasteur, Paris, France; Wellcome Trust Center for Research in Clinical Tropical Medicine, Division of Medicine, Imperial College London, UK

^* To whom correspondence should be addressed. Email: katalin.wilkinson{at}imperial.ac.uk.

	Abstract

The genetically detoxified Bordetella pertussis adenylate cyclase is a promising delivery system for immunodominant tuberculosis antigens in interferon gamma release assays. This system has not been evaluated in HIV-infected persons in high tuberculosis prevalence areas. A whole blood interferon gamma release assay using 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 Khayelitisha township, Cape Town, South Africa. Results were compared to tuberculin skin test in 41 HIV-positive and 42 HIV-negative asymptomatic persons in addition to 36 HIV-positive persons with recently diagnosed smear/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 interferon gamma responses to the tuberculosis antigens (with or without delivery by adenylate cyclase) were combined, a significantly higher number of patients were scored positive compared to 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 this population are infected with tuberculosis, which is of significant public health importance.