Validating a Novel Functional Correlate of Immune Protection of Tuberculosis

This C-TRIUMPH study is a longitudinal assessment of PBMC samples of progressors and non-progressors among adult household contacts of active TB patients. The purpose of the study is to probe the functional diversity of T cell responses to several of the antigens encoded by Mtb simultaneously in subjects covering the clinical spectrum of tuberculosis, including adults with: latent TB, extrapulmonary TB and pulmonary TB.

Primary Objectives 

• Validate using advanced 16-colour flow cytometry in cTRIUMPh longitudinal samples, if TB-free adults who progress to TB (cohort 1), is associated with loss of DosR antigen specific, Th17 regulatory CD4 T cell responses with a concomitant increase in DosR antigen specific, Th17 proinflammatory CD4 T cells.  
• Further validate using advanced 16-colour flow cytometry in cTRIUMPh longitudinal samples of adults who do not progress to TB in the same time frame as cohort 1 (cohort 2), is associated with preservation of DosR antigen specific, Th17 regulatory CD4 T cell responses.  
• Undertake a comparative analysis of the DosR antigen-specific Th17 regulatory and proinflammatory response in cohorts 1 and 2 with responses to the Mycobacterium tuberculosis (Mtb) immunodominant secretory antigen ESAT6/CFP10 as well as recall response to stimulation with BCG vaccine, which can stimulate responses to multiple T cell epitopes of Mtb antigens.