Publications by authors named "Tereza Masonou"

5 Publications

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Defining the Role of Cellular Immune Signatures in Diagnostic Evaluation of Suspected Tuberculosis.

J Infect Dis 2021 Jul 31. Epub 2021 Jul 31.

TB Research Centre, National Heart and Lung Institute, Imperial College London, London, United Kingdom.

Background: Diagnosis of paucibacillary tuberculosis (TB) including extrapulmonary TB is a significant challenge, particularly in high-income, low-incidence settings. Measurement of Mycobacterium tuberculosis (Mtb)-specific cellular immune signatures by flow cytometry discriminates active TB from latent TB infection (LTBI) in case-control studies; however, their diagnostic accuracy and clinical utility in routine clinical practice is unknown.

Methods: Using a nested case-control study design within a prospective multicenter cohort of patients presenting with suspected TB in England, we assessed diagnostic accuracy of signatures in 134 patients who tested interferon-gamma release assay (IGRA)-positive and had final diagnoses of TB or non-TB diseases with coincident LTBI. Cellular signatures were measured using flow cytometry.

Results: All signatures performed less well than previously reported. Only signatures incorporating measurement of phenotypic markers on functional Mtb-specific CD4 T cells discriminated active TB from non-TB diseases with LTBI. The signatures measuring HLA-DR+IFNγ + CD4 T cells and CD45RA-CCR7-CD127- IFNγ -IL-2-TNFα + CD4 T cells performed best with 95% positive predictive value (95% confidence interval, 90-97) in the clinically challenging subpopulation of IGRA-positive but acid-fast bacillus (AFB) smear-negative TB suspects.

Conclusions: Two cellular immune signatures could improve and accelerate diagnosis in the challenging group of patients who are IGRA-positive, AFB smear-negative, and have paucibacillary TB.
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http://dx.doi.org/10.1093/infdis/jiab311DOI Listing
July 2021

Human models for COVID-19 research.

J Physiol 2021 09 17;599(18):4255-4267. Epub 2021 Aug 17.

GOS Institute of Child Health, University College London, London, UK.

Currently, therapeutics for COVID-19 are limited. To overcome this, it is important that we use physiologically relevant models to reproduce the pathology of infection and evaluate the efficacy of antiviral drugs. Models of airway infection, including the use of a human infection challenge model or well-defined, disease relevant in vitro systems can help determine the key components that perpetuate the severity of the disease. Here, we briefly review the human models that are currently being used in COVID-19 research and drug development.
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http://dx.doi.org/10.1113/JP281499DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8447334PMC
September 2021

Immunodiagnosis of active tuberculosis.

Expert Rev Respir Med 2019 06 28;13(6):521-532. Epub 2019 May 28.

a Tuberculosis Research Centre, National Heart and Lung Institute , Imperial College London , London , UK.

: There is an unmet clinical need for improved diagnostic tests for active tuberculosis (TB) to provide high sensitivity for all cases, accelerate time to diagnosis and ensure timely and appropriate treatment. Whilst the measurement of -specific immune responses is widely used for detecting infection in the absence of TB symptoms (i.e. latent TB infection), there is currently no role for immunodiagnostics in active TB disease. This is primarily due to insufficient sensitivity, and an inability to discriminate between active disease and controlled, latent TB infection. : In this review, we focus on recent developments in the use of immune-based tests to provide a point of care test for the rule-in or rule-out of active TB. : Recent studies have demonstrated that second-generation IGRAs have the potential to rule-out active TB, particularly in low burden settings. Newer technological platforms, including systems serology and flow cytometry, offer the means to measure specific specific immune signatures which have been shown to have a high level of accuracy for active TB. However, it is now crucial that new and promising test undergo validation in clinically relevant cohorts which include the full spectrum of TB patients and differential diagnoses.
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http://dx.doi.org/10.1080/17476348.2019.1615888DOI Listing
June 2019

CD4+ T cell cytokine responses to the DAR-901 booster vaccine in BCG-primed adults: A randomized, placebo-controlled trial.

PLoS One 2019 23;14(5):e0217091. Epub 2019 May 23.

Geisel School of Medicine, Hanover, NH, United States of America.

Background: DAR-901 is an inactivated whole cell tuberculosis booster vaccine, prepared using a new scalable, broth-grown method from the master cell bank of SRL172, a vaccine previously shown to prevent tuberculosis. This study examined whether DAR-901 (a) induces CD4+ T cell cytokine profiles previously proposed as correlates of protection and (b) has a specific vaccine-induced immunological signature compared to BCG or placebo.

Methods: We analysed CD4+ T cell cytokine immune responses from 10 DAR-901 recipients, 9 BCG recipients and 9 placebo recipients from the Phase I DAR-901 MDES trial. In that study, HIV-negative, IGRA-negative participants with prior BCG immunization were randomized (double-blind) to receive three intradermal injections of DAR-901 or saline placebo or two injections of saline placebo followed by an intradermal injection of BCG. Antigen-specific functional and phenotypic CD4+ T cell responses along with effector phenotype of responder cells were measured by intracellular cytokine staining.

Results: DAR-901 recipients exhibited increased DAR-901 antigen-specific polyfunctional or bifunctional T cell responses compared to baseline. Vaccine specific CD4+ IFNγ, IL2, TNFα and any cytokine responses peaked at 7 days post-dose 3. Th1 responses predominated, with most responder cells exhibiting a polyfunctional effector memory phenotype. BCG induced greater CD4+ T cell responses than placebo while the more modest DAR-901 responses did not differ from placebo. Neither DAR-901 nor BCG induced substantial or sustained Th17 /Th22 cytokine responses.

Conclusion: DAR-901, a TB booster vaccine grown from the master cell bank of SRL 172 which was shown to prevent TB, induced low magnitude polyfunctional effector memory CD4+ T cell responses. DAR-901 responses were lower than those induced by BCG, a vaccine that has been shown ineffective as a booster to prevent tuberculosis disease. These results suggest that induction of higher levels of CD4+ cytokine stimulation may not be a critical or pre-requisite characteristic for candidate TB vaccine boosters.

Trial Registration: ClinicalTrials.gov NCT02063555.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0217091PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6532882PMC
January 2020
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