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© Research
Publication : Clinical and vaccine immunology : CVI

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

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Clinical and vaccine immunology : CVI - 23 May 2007

Connell TG, Shey MS, Seldon R, Rangaka MX, van Cutsem G, Simsova M, Marcekova Z, Sebo P, Curtis N, Diwakar L, Meintjes GA, Leclerc C, Wilkinson RJ, Wilkinson KA

Link to Pubmed [PMID] – 17522328

Clin. Vaccine Immunol. 2007 Jul;14(7):847-54

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.

http://www.ncbi.nlm.nih.gov/pubmed/17522328