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Infection and Immunity, January 2004, p. 381-388, Vol. 72, No. 1
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.1.381-388.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Immune Responses to Mycobacterial Antigens in the Gambian Population: Implications for Vaccines and Immunodiagnostic Test Design

Johan Vekemans,1,2* Martin O. C. Ota,1 Jackson Sillah,1 Katherine Fielding,3 Mark R. Alderson,4 Yasir A. W. Skeiky,4 Wilfried Dalemans,5 Keith P. W. J. McAdam,1 Christian Lienhardt,1 and Arnaud Marchant1,{dagger}

Medical Research Council Laboratories, Fajara, The Gambia,1 Université Libre de Bruxelles, Brussels,2 GlaxoSmithKline Biologicals, Rixensart, Belgium,5 London School of Tropical Medicine and Hygiene, London, United Kingdom,3 Corixa Corporation, Seattle, Washington4

Received 20 May 2003/ Returned for modification 2 July 2003/ Accepted 13 October 2003

Recombinant immunodominant mycobacterial antigens are needed for the development of new vaccines and immunodiagnostic tools for use against tuberculosis. Ubiquitous exposure to mycobacteria in tropical countries could influence vaccine-induced immunity and the specificity of tuberculosis immunodiagnosis. For this study conducted in The Gambia, cellular immune responses to recombinant mycobacterial antigens were characterized in Mycobacterium bovis BCG-vaccinated and nonvaccinated infants, adult community controls, household contacts, health care workers, and tuberculosis patients. Neonatal BCG vaccination induced gamma interferon (IFN-{gamma}) responses to Mtb8.4, Mtb32-C, Mtb39A, Mtb9.9A, and Mtb32-N, but not CFP-10 (Mtb11) and {alpha}-crystallin (Mtb16). Exposure to Mycobacterium tuberculosis in household contacts and health care workers was associated with high responses to CFP-10 and {alpha}-crystallin. Generally, low IFN-{gamma} responses were found in tuberculosis patients. These results suggest that Mtb8.4, Mtb32-C, Mtb39A, Mtb9.9A, and Mtb32-N may be used in a subunit vaccine to boost BCG-induced immunity. While CFP-10 and {alpha}-crystallin are promising candidates for the immunodiagnosis of M. tuberculosis infection or for vaccine use, disease-associated immunosuppression may prevent IFN-{gamma} immunodiagnosis of more advanced tuberculosis.

* Corresponding author. Mailing address: Université Libre de Bruxelles, 130 Rue des Alliés, 1190 Brussels, Belgium. Phone: 32-2-347-67-51. Fax: 32-2-675-78-78. E-mail: Johan.Vekemans{at}ulb.ac.be.

Editor: S. H. E. Kaufmann

{dagger} Present address: Human Immunology Unit, Weatherall Institute of Molecular Medicine, OX3 9SD, Oxford, United Kingdom.

Infection and Immunity, January 2004, p. 381-388, Vol. 72, No. 1
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.1.381-388.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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