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

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Abstract
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-γ) responses to Mtb8.4, Mtb32-C, Mtb39A, Mtb9.9A, and Mtb32-N, but not CFP-10 (Mtb11) and α-crystallin (Mtb16). Exposure to Mycobacterium tuberculosis in household contacts and health care workers was associated with high responses to CFP-10 and α-crystallin. Generally, low IFN-γ 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 α-crystallin are promising candidates for the immunodiagnosis of M. tuberculosis infection or for vaccine use, disease-associated immunosuppression may prevent IFN-γ immunodiagnosis of more advanced tuberculosis.

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