IFN-γ release assays (e.g. QuantiFERON (QFT)) are widely used for diagnosis of Mycobacterium tuberculosis (Mtb) infection. T-cell responses against QFT antigens ESAT6 and CFP10 are highly Mtb specific but previous studies indicated suboptimal assay sensitivity. Hence, newly improved diagnostic methods and the evaluation of other immunogenic antigens are needed. Targeting host T cell immune response specifically against DosR regulon encoded (latency) antigens of M. tuberculosis may be an important biomarker for the latently infected (LTBI). As this antigen specific T-cell response may serve as a potential indicator for Mtb infection and thus may contribute immunological effects that avoid Mtb reactivation and disease progression.
The focus of this project is to employ advanced multi-colour flow cytometry, functional assays and serodiagnostic techniques to address the following;
- Optimisation of in vitro culture conditions to detect T-cell responses against both secretory and latent Mtb antigens patients with different stages of Mtb infection.
- Serve as the basis of selecting promising latency antigens candidates that can unequivocally predict protective immunity against Mtb infection.
- To evaluate T cell response to Mtb DOSR-regulon-encoded antigens (latency antigens) in latent and active tuberculosis.
The understanding of the host immune response directed against products produced by latency induced genes may help improve the sensitivity and specificity of standard clinical tests and most importantly used as adjuvants for a more potent Mtb vaccine.
(by Ernest Adankwah)