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Order Articulavirales
Published in Paul Pumpens, Peter Pushko, Philippe Le Mercier, Virus-Like Particles, 2022
Paul Pumpens, Peter Pushko, Philippe Le Mercier
The early secretory antigenic target 6 protein (ESAT-6) epitope from Mycobacterium tuberculosis, a potent T-cell epitope of 20 aa residues in length, was engineered into the antigenic region B of the HA from strain A/New Caledonia/20/99 H1N1 (Krammer et al. 2010). The VLPs consisting of M1 and ESAT6-HA or HA were produced in insect cells and subjected to immunization studies in mice. The high serum antibody titers detected against the ESAT-6 clearly demonstrated the feasibility of influenza A VLPs serving as an efficient platform for the presentation of valuable foreign immune epitopes. As mentioned earlier, the influenza VLPs could incorporate the VSV protein G (Latham and Galarza 2001).
BCG and Other Vaccines
Published in Lloyd N. Friedman, Martin Dedicoat, Peter D. O. Davies, Clinical Tuberculosis, 2020
Three fusion protein/adjuvant vaccine candidates: Hybrid 1/IC31, Hybrid 4/IC31, and Hybrid 56/IC31 were designed by the Statens Serum Institut (SSI) in Copenhagen. H1/IC31 contains the fusion protein of Ag85B and ESAT-6 adjuvanted to a system combining the antibacterial peptide KLK with a synthetic Toll-like receptor (TLR)-9 agonist (ODN1a). This vaccine was safe in healthy, prior, or latently TB-infected and HIV-infected adults, and induced a robust and durable CD4+ T-cell response.165–167 However, the inclusion of ESAT-6 potentially confounds the IGRA diagnostic assay which uses a T-cell response to ESAT-6 and CFP-10 as evidence of M.tb infection. Indeed, a recent study found that 17% of participants receiving high-dose H1/IC31 developed a positive response to the QuantiFERON TB Gold in-tube assay.165 H4/IC31 (AERAS-404) circumvents this issue by replacing ESAT-6 with TB10.4, while still demonstrating moderate protective efficacy in preclinical models.168,169 In a recent phase II trial conducted in South African adolescents, H4/IC31 showed no protection against initial infection, and a non-statistically significant trend toward reduced sustained M.tb infections.57
Inflammation and Infection
Published in Manoj Ramachandran, Tom Nunn, Basic Orthopaedic Sciences, 2018
Vikas Khanduja, Sertazniel Singhkang, Manoj Ramachandran
There are several problems with skin tests, which has led to the development of selective immunological interferon gamma tests (IGTs). These IGTs identify three different tuberculosis antigens – early secretion antigen target 6 (ESAT 6), culture filtrate protein 10 (CFP-10) and tb7.7 – from whole blood samples. IGT shows a stronger correlation with exposure than Mantoux tests, but NICE guidelines recommend a two-step approach of an initial Mantoux test followed by an IGT to confirm positivity.
Synergy between Th1 and Th2 responses during Mycobacterium tuberculosis infection: A review of current understanding
Published in International Reviews of Immunology, 2019
On the other hand, out of an estimated 2 billion people believed to have Mtb infection, only 10–12% develops clinical disease. The fact that the vast majority (over 90%) of Mtb infected individuals contain infection without apparent development of disease implies that natural immunity plays a central role. Therefore, it is possible to identify those host immune factors involved in response to infection and use them as biomarkers to guide development of vaccines [6]. In this regard, a strong association between decreased IFN-γ expression and development of clinical disease and increased expression of IFN-γ following successful chemotherapy of TB patients is a common experience [7–10]. Based on the above understanding, there were studies to determine protective molecular markers in cohorts of house hold contacts (HHCs) in TB high endemic setting. Using ESAT-6 the VASCEL group identified that those TB contacts with increased expression of ESAT-6-specific IFN-γ were at most risk of developing progressive disease [6]. In a study involving pulmonary TB patients (PTBP), their household contacts (HHCs), and community control (CCs), our group has found that IFN-γ against ESAT-6/CFP-10 was the highest in PTBP compared to HHCs and CCs, implying that elevated levels of IFN-γ may indicate risk of disease, but not necessarily immune protection [10,11].
Prevalence of positive QuantiFERON gold in-tube testing in hidradenitis suppurativa
Published in Journal of Dermatological Treatment, 2018
Tina Boortalary, Kanchan Misra, Sean McNish, Derek Jones, Victoria K. Shanmugam
IGRA are commonly used to screen for mTB exposure (17). These assays assess the cell-mediated response to mTB antigens. The QuantiFERON gold in tube (QFT-GIT) assay (Qiagen, Hilden, Germany) is an ELISA-based assay which quantifies IFN-γ release in response to three mTB antigens (ESAT-6, CFP-10, and TB7.7). The result is reported as quantification of IFN-γ in international units (IU) per mL. The test is considered positive if the IFN-γ response to TB antigens is above the test cutoff after subtracting the background IFN-γ response in the negative control. An alternative IGRA, the TSPOT®.TB (Oxford Immunotec, UK), is also commercially available and uses ELISPOT assay to measure the number of antimycobacterial effector T-cells that produce IFN-γ in a sample of blood. The mTB specific antigen peptides that are assessed in the TSPOT®.TB assay are the ESAT-6 and CFP-10.
Diagnosis of Ocular Tuberculosis
Published in Ocular Immunology and Inflammation, 2018
Marcus Ang, Daniel V. Vasconcelos-Santos, Kusum Sharma, Massimo Accorinti, Aman Sharma, Amod Gupta, Narsing A. Rao, Soon-Phaik Chee
There are two commercially available IGRAs: the QuantiFERON-Gold In-Tube (QFT, Cellestis Inc, Carnegie, Australia), which is a whole blood enzyme-linked immunosorbent assay (ELISA) measuring concentration of IFN-γ secreted in response to stimulation with the ESAT-6, CFP-10 and TB77 antigens, as well as the T-SPOT.TB (Oxford Immunotec, Abingdon, UK), which is a T cell-based enzyme-linked immunospot assay (ELISPOT) measuring T-cell spot formation following exposure to the ESAT-6 and CFP-10 antigens.41 As these antigens are absent from all BCG strains and most NTM, both QFT and T-SPOT.TB impart greater specificity than tests using PPD, which is reflected in most studies.42 T-SPOT.TB also differs from QFT in that the former involves harvesting and counting viable peripheral mononuclear blood cells (PMBCs) that release IFN-γ; while the latter uses an enzyme-linked immunosorbent assay (ELISA) to quantify IFN-γ release from T-cells in whole blood.43 The technique used in T-SPOT.TB may provide better resolution of blood samples with reduced T-cell numbers (e.g., samples from immunocompromised individuals) that would usually give indeterminate QFT results.44 There is increasing evidence that suggests that IGRAs are more specific,45 and/or accurate for the diagnosis of TB compared with TST.39,42,46,47 Improved specificity of IGRAs over TST has been shown to reduce unnecessary anti-TB treatment (ATT).48–50