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Order Blubervirales: Core Protein
Published in Paul Pumpens, Peter Pushko, Philippe Le Mercier, Virus-Like Particles, 2022
Paul Pumpens, Peter Pushko, Philippe Le Mercier
Concerning tuberculosis, Dhanasooraj et al. (2013, 2016) inserted culture filtrate protein 10 (CFP-10) of Mycobacterium tuberculosis, an important vaccine candidate, into the HBcΔ MIR. The authors compared the pure protein, a mixture of antigens, and the chimeric HBcΔ-CFP10 VLPs by immunization of mice and found that the chimeric VLPs generated the stronger antigen-specific immune response in a Th1-dependent manner.
BCG and Other Vaccines
Published in Lloyd N. Friedman, Martin Dedicoat, Peter D. O. Davies, Clinical Tuberculosis, 2020
An alternative approach is to use attenuated M.tb in which virulence-related genes have been deleted while conserving major immunodominant antigens such as early-secreted antigen-6 (ESAT-6) and culture filtrate protein-10 (CFP-10) that are absent in BCG. In light of safety concerns regarding advancing attenuated strains of M.tb to clinical evaluation (particularly in immunocompromised populations), two international meetings with regulators and vaccine developers coordinated by the WHO led to a set of recommendations on the construction and preclinical safety testing of these vaccines.144,145 MTBVAC, which contains two independent deletion mutations in the virulence genes phoP and fadD26, fulfills the Geneva consensus safety requirements and is the first of its kind to enter clinical trials. This vaccine demonstrated superior protection to BCG in guinea pigs and NHPs,146,147 and in a recent phase I clinical trial was found to be as safe as BCG, and comparably immunogenic.148 A phase Ib/IIa trial in adults with and without LTBI is underway (NCT02933281).
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.
Clinical utilization of multiple antibodies of Mycobacterium tuberculosis for serodiagnosis evaluation of tuberculosis: a retrospective observational cohort study
Published in Annals of Medicine, 2023
DeWu Bi, ChaoJuan Liang, XiaoXian Huang, HuiDan Pan, Yue Qin, XiMing Shi, YunHua Tang, Ying Wang, MingMei Zhao, JianYan Lin, ZhouHua Xie, LeMin Wen, ChaoYou Chen, XiKe Tang, XiaoCheng Luo, HongHua Shao, XiaoLu Luo
To the best of our knowledge, this is the largest observational cohort study that characterized clinical practice to evaluate and compare the diagnostic properties of antibodies against M. tuberculosis antigens, including 16kD, 38kD, CFP-10, LAM, and Rv1636, in the assessment of suspected active tuberculosis. In accordance with previous findings on different antigens [13, 17, 19], antigen-specific antibodies contribute to the immune response to infection and defence against M. tuberculosis. Most cases of possible tuberculosis in high-burden countries are active tuberculosis [12]. Similar to previous findings, the diagnostic sensitivity for active tuberculosis was low for all antibodies against M. tuberculosis antigens in our study. Our study suggests that the low sensitivity and negative likelihood ratios of procurable and antibodies against M. tuberculosis antigen probes indicate that a negative result cannot rule out a diagnosis of active tuberculosis. However, considering that antigen CFP-10 is a secreted protein of pathogenic mycobacteria in the early stages of infection [20] and is absent in nontuberculous mycobacteria or BCG vaccine, it had a high specificity for diagnosing active tuberculosis. Furthermore, the specificity of antibodies against 16kD, 38kD, and Rv1636 increased to approximately 90–93% in patients with latent tuberculosis and nontuberculous mycobacterial infections. The high specificity of antibodies against 16kD, 38kD, and Rv1636 provided high positive likelihood ratios, validating the rule-in of active tuberculosis. Thus, a positive antibody against 16kD, 38kD, and Rv1636 results may contribute to ensuring a confident diagnosis of active tuberculosis in the differential diagnosis in a condition such that latent tuberculosis and nontuberculous mycobacterium have a low prevalence. However, antibodies against M. tuberculosis antigens are used in clinical practice to evaluate the possibility of active tuberculosis but not for possible tuberculosis.