Correlates of protective immunity to Mycobacterium tuberculosis in humans

Correlates of protective immunity to Mycobacterium tuberculosis in humans a re desirable for identifying protective antigens, demonstrating the immunog enicity of a vaccine candidate and its potential efficacy, and permitting o ptimization of the dose, vehicle, adjuvant, and schedule of immunization. p otential correlates can be proposed on the basis of animal models and ex vi vo/in vitro studies in humans. Most critical is their validation; ultimate validation will require correlation with protection in a phase IU efficacy trial of an effective vaccine. Other approaches, however, can allow selecti on of the most promising correlates for inclusion in phase I and II and, ul timately, phase III vaccine trials. Current data from experimental models a nd studies of patients with pulmonary tuberculosis and their household cont acts indicate that Mycobacterium tuberculosis-stimulated whole-blood produc tion of interferon-gamma, although imperfect, is the best available correla te. Nonetheless, further refinement of this assay and additional studies of more complex assays that model M. tuberculosis killing and cytotoxic T lym phocyte activity are warranted, During planning of a vaccine trial, the bes t available correlates of immunity can be selected for inclusion.