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The Early secreted antigenic target 6 kDa (ESAT-6) and 10-kDa culture filtrate protein (CFP-10) complex is a potent heterodimeric virulence factor secreted by Mycobacterium tuberculosis via the ESX-1 Type VII secretion system (UniProt P9WNK7, P9WNK5). These proteins are encoded within the Region of Difference 1 (RD1), a genomic segment present in virulent M. tuberculosis but notably absent in the attenuated Mycobacterium bovis BCG vaccine strain and most non-tuberculous mycobacteria (Brodin et al., 2004). The complex functions primarily by disrupting host phagosomal membranes, facilitating the escape of the bacteria into the host cell cytosol and modulating immune signaling to favor bacterial persistence (De Leon et al., 2012; PubMed: 17464067). Because of its high immunogenicity and absence in the BCG strain, the ESAT-6/CFP-10 fusion or complex is a cornerstone for diagnostic Interferon-Gamma Release Assays (IGRAs), such as QuantiFERON-TB Gold, which differentiate between TB infection and prior BCG vaccination (CDC, 2021). Furthermore, this protein complex is a primary target for novel recombinant subunit vaccines, including GamTBvac and the H-series (H1, H56) candidates, currently under investigation to improve global tuberculosis control (ClinicalTrials.gov NCT04975763; WHO TB Vaccine Pipeline).
Induction of antigen-specific T-cell mediated immune response, primarily through the stimulation of interferon-gamma (IFN-g) production for diagnostic detection or vaccine-mediated protection.
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