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  1. Article ; Online: Gene expression profiling reveals insights into infant immunological and febrile responses to group B meningococcal vaccine

    Daniel O’Connor / Marta Valente Pinto / Dylan Sheerin / Adriana Tomic / Ruth E Drury / Samuel Channon‐Wells / Ushma Galal / Christina Dold / Hannah Robinson / Simon Kerridge / Emma Plested / Harri Hughes / Lisa Stockdale / Manish Sadarangani / Matthew D Snape / Christine S Rollier / Michael Levin / Andrew J Pollard

    Molecular Systems Biology, Vol 16, Iss 11, Pp n/a-n/a (2020)

    2020  

    Abstract: Abstract Neisseria meningitidis is a major cause of meningitis and septicaemia. A MenB vaccine (4CMenB) was licensed by the European Medicines Agency in January 2013. Here we describe the blood transcriptome and proteome following infant immunisations ... ...

    Abstract Abstract Neisseria meningitidis is a major cause of meningitis and septicaemia. A MenB vaccine (4CMenB) was licensed by the European Medicines Agency in January 2013. Here we describe the blood transcriptome and proteome following infant immunisations with or without concomitant 4CMenB, to gain insight into the molecular mechanisms underlying post‐vaccination reactogenicity and immunogenicity. Infants were randomised to receive control immunisations (PCV13 and DTaP‐IPV‐Hib) with or without 4CMenB at 2 and 4 months of age. Blood gene expression and plasma proteins were measured prior to, then 4 h, 24 h, 3 days or 7 days post‐vaccination. 4CMenB vaccination was associated with increased expression of ENTPD7 and increased concentrations of 4 plasma proteins: CRP, G‐CSF, IL‐1RA and IL‐6. Post‐vaccination fever was associated with increased expression of SELL, involved in neutrophil recruitment. A murine model dissecting the vaccine components found the concomitant regimen to be associated with increased gene perturbation compared with 4CMenB vaccine alone with enhancement of pathways such as interleukin‐3, ‐5 and GM‐CSF signalling. Finally, we present transcriptomic profiles predictive of immunological and febrile responses following 4CMenB vaccine.
    Keywords paediatrics ; proteomics ; systems biology ; transcriptomics ; vaccines ; Biology (General) ; QH301-705.5 ; Medicine (General) ; R5-920
    Subject code 610
    Language English
    Publishing date 2020-11-01T00:00:00Z
    Publisher Wiley
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Discovery and validation of a three-gene signature to distinguish COVID-19 and other viral infections in emergency infectious disease presentations

    Ho Kwong Li, MRCP / Myrsini Kaforou, PhD / Jesus Rodriguez-Manzano, PhD / Samuel Channon-Wells, MMath / Ahmad Moniri, MEng / Dominic Habgood-Coote, MSc / Rishi K Gupta, MRCP / Ewurabena A Mills, BSc / Dominique Arancon, BSN / Jessica Lin, MRes / Yueh-Ho Chiu, PhD / Ivana Pennisi, MSc / Luca Miglietta, MSc / Ravi Mehta, MRCP / Nelofar Obaray, PhD / Jethro A Herberg, PhD / Victoria J Wright, PhD / Pantelis Georgiou, PhD / Laura J Shallcross, PhD /
    Alexander J Mentzer, DPhil / Michael Levin, ProfPhD / Graham S Cooke, ProfDPhil / Mahdad Noursadeghi, ProfPhD / Shiranee Sriskandan, ProfPhD

    The Lancet Microbe, Vol 2, Iss 11, Pp e594-e

    a case-control and observational cohort study

    2021  Volume 603

    Abstract: Summary: Background: Emergency admissions for infection often lack initial diagnostic certainty. COVID-19 has highlighted a need for novel diagnostic approaches to indicate likelihood of viral infection in a pandemic setting. We aimed to derive and ... ...

    Abstract Summary: Background: Emergency admissions for infection often lack initial diagnostic certainty. COVID-19 has highlighted a need for novel diagnostic approaches to indicate likelihood of viral infection in a pandemic setting. We aimed to derive and validate a blood transcriptional signature to detect viral infections, including COVID-19, among adults with suspected infection who presented to the emergency department. Methods: Individuals (aged ≥18 years) presenting with suspected infection to an emergency department at a major teaching hospital in the UK were prospectively recruited as part of the Bioresource in Adult Infectious Diseases (BioAID) discovery cohort. Whole-blood RNA sequencing was done on samples from participants with subsequently confirmed viral, bacterial, or no infection diagnoses. Differentially expressed host genes that met additional filtering criteria were subjected to feature selection to derive the most parsimonious discriminating signature. We validated the signature via RT-qPCR in a prospective validation cohort of participants who presented to an emergency department with undifferentiated fever, and a second case-control validation cohort of emergency department participants with PCR-positive COVID-19 or bacterial infection. We assessed signature performance by calculating the area under receiver operating characteristic curves (AUROCs), sensitivities, and specificities. Findings: A three-gene transcript signature, comprising HERC6, IGF1R, and NAGK, was derived from the discovery cohort of 56 participants with bacterial infections and 27 with viral infections. In the validation cohort of 200 participants, the signature differentiated bacterial from viral infections with an AUROC of 0·976 (95% CI 0·919−1·000), sensitivity of 97·3% (85·8−99·9), and specificity of 100% (63·1−100). The AUROC for C-reactive protein (CRP) was 0·833 (0·694−0·944) and for leukocyte count was 0·938 (0·840−0·986). The signature achieved higher net benefit in decision curve analysis than either CRP or leukocyte ...
    Keywords Medicine (General) ; R5-920 ; Microbiology ; QR1-502
    Subject code 572
    Language English
    Publishing date 2021-11-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

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    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

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