Immune responses to mycobacterial antigens in the Gambian population: implications for vaccines and immunodiagnostic test design

冈比亚人群对分枝杆菌抗原的免疫反应:对疫苗和免疫诊断测试设计的影响

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作者:Johan Vekemans, Martin O C Ota, Jackson Sillah, Katherine Fielding, Mark R Alderson, Yasir A W Skeiky, Wilfried Dalemans, Keith P W J McAdam, Christian Lienhardt, Arnaud Marchant

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-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.

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