Abstract Rationale Despite major progress in tuberculosis (TB) control, early immunological mechanisms that define protection versus infection remain poorly understood. The TBVAC Study integrates field-based contact tracing with immunological profiling to identify early immune correlates of protection against Mycobacterium tuberculosis (M.tb) among household contacts in The Gambia. Methods The study is being conducted across 12 health facilities in the Greater Banjul Area. Newly diagnosed GeneXpert-confirmed pulmonary TB index cases were identified, and their household contacts traced within 14 days of treatment initiation. Adults aged 18-65 years with close exposure (shared household ≤ two weeks before diagnosis) were enrolled after informed consent. Whole blood, plasma, and nasopharyngeal samples were collected for immunological, molecular, and transcriptional analyses. PBMCs are characterized for cytokine and gene-expression signatures to identify early immune correlates of protection. Participants are followed longitudinally at 6 and 12 weeks to monitor infection conversion using IGRA and molecular testing. Results To date, 112 GeneXpert confirmed pulmonary TB index cases (70 male, 42 female) have been identified across 12 participating facilities. Among these, 3 (2+) and 2 (3+) were smear-positive, while 39 (35%) exhibited medium and 68 (61%) high bacterial loads on GeneXpert. From these, 213 household contacts were screened, and 200 successfully enrolled. Among contacts, 70% were female and 30% male; 63% shared the same house and 37% the same room with index cases, reflecting high exposure intensity. Baseline immunological analysis (QuantiFERON) shows 64% negative, 33% positive, and 3% indeterminate results. Longitudinal IGRA monitoring indicates 23 resistors, 3 reverters, and 2 converters at week 12. Flow cytometry reveals distinct CD4+ and CD8+ T-cell activation profiles (CD69+, HLA-DR+) with cytokine expression (IFN-γ, TNF-α, IL-17) suggesting early immune activation. Laboratory analyses are ongoing to identify immune correlates of protection; results will be available by the time of presentation. Conclusion The TBVAC Study demonstrates the feasibility of integrating community-based TB contact tracing with immunological research in The Gambia. Findings highlight sex differences in exposure, early immune activation patterns, and the potential of IGRA conversion as a biomarker for early infection. Recruitment is complete, and follow-up is ongoing. This abstract is funded by: None
Jatta et al. (Fri,) studied this question.