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  1. Article ; Online: Effective Multivalent Oriented Presentation of Meningococcal NadA Antigen Trimers by Self-Assembling Ferritin Nanoparticles

    Daniele Veggi / Lucia Dello Iacono / Enrico Malito / Giulietta Maruggi / Fabiola Giusti / Panchali Goswami / Werner Pansegrau / Sara Marchi / Sara Tomei / Enrico Luzzi / Matthew James Bottomley / Federico Fontani / Ilaria Ferlenghi / Maria Scarselli

    International Journal of Molecular Sciences, Vol 24, Iss 6183, p

    2023  Volume 6183

    Abstract: The presentation of viral antigens on nanoparticles in multivalent arrays has emerged as a valuable technology for vaccines. On the nanoparticle surface, highly ordered, repetitive arrays of antigens can mimic their geometric arrangement on virion ... ...

    Abstract The presentation of viral antigens on nanoparticles in multivalent arrays has emerged as a valuable technology for vaccines. On the nanoparticle surface, highly ordered, repetitive arrays of antigens can mimic their geometric arrangement on virion surfaces and elicit stronger humoral responses than soluble viral antigens. More recently, bacterial antigens have been presented on self-assembling protein nanoparticles and have elicited protective antibody and effective T-helper responses, further supporting the nanoparticle platform as a universal approach for stimulating potent immunogenicity. Here, we present the rational design, structural analysis, and immunogenicity of self-assembling ferritin nanoparticles displaying eight copies of the Neisseria meningitidis trimeric adhesin NadA. We engineered constructs consisting of two different NadA fragments, head only and head with stalk, that we fused to ferritin and expressed in Escherichia coli . Both fusion constructs self-assembled into the expected nanoparticles as determined by Cryo electron microscopy. In mice, the two nanoparticles elicited comparable NadA antibody levels that were 10- to 100-fold higher than those elicited by the corresponding NadA trimer subunits. Further, the NadAferritin nanoparticles potently induced complement-mediated serum bactericidal activity. These findings confirm the value of self-assembling nanoparticles for optimizing the immunogenicity of bacterial antigens and support the broad applicability of the approach to vaccine programs, especially for the presentation of trimeric antigens.
    Keywords nanoparticles ; ferritin ; bacterial antigen ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 620
    Language English
    Publishing date 2023-03-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Improving the documentation quality of point-of-care ultrasound scans in the emergency department

    Shadman Aziz / James Bottomley / Vasant Mohandas / Arif Ahmad / Gemma Morelli / Sam Thenabadu

    BMJ Open Quality, Vol 9, Iss

    2020  Volume 1

    Abstract: A point-of-care ultrasound scan (POCUS) is a core element of the Royal College of Emergency Medicine (RCEM) specialty training curriculum. However, POCUS documentation quality can be poor, especially in the time-pressured environment of the emergency ... ...

    Abstract A point-of-care ultrasound scan (POCUS) is a core element of the Royal College of Emergency Medicine (RCEM) specialty training curriculum. However, POCUS documentation quality can be poor, especially in the time-pressured environment of the emergency department (ED). A survey of 10 junior ED clinicians at the Princess Royal University Hospital (PRUH) found that total POCUS documentation was as low as 38% in some examinations.This quality improvement project aimed to increase the coverage and quality of POCUS documentation in the ED. This was done by using a plan-do-study-act (PDSA) regime to improve the quality of POCUS documentation from the original baseline to 80%. There were three discreet PDSA cycles and the interventions included improving education and training about POCUS documentation and the introduction of an original proforma, which incorporated six minimum requirements for POCUS documentation as per the joint RCEM and Royal College of Radiologists (RCR) guidelines for POCUS documentation (patient details, indications, findings, conclusions, signature and date).The project team audited the quality of all documented scans in the resuscitation department of the PRUH against the RCEM/RCR guidelines at baseline and following three discrete PDSA cycles. This was done over an 8-week period, spanning 696 attendances to the resuscitation area of the ED and 42 documented POCUS examinations.Quality recording of the six RCEM/RCR elements of POCUS documentation was poor at baseline but improved following three successful PDSA cycles. There was a demonstrated improvement in five of six documentation elements: patient details on POCUS documentation increased from 53.3% to the 66.7%, indication from 60.0% to 66.7%, conclusion from 13.0% to 83.0%, signature from 86.7% to 100.0% and date from 46.7% to 66.7%.These results suggest that the introduction of a proforma and a vigorous education strategy are effective ways to improve the quality of documentation of ED POCUS.
    Keywords Medicine (General) ; R5-920
    Subject code 360
    Language English
    Publishing date 2020-03-01T00:00:00Z
    Publisher BMJ Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Transplantation Without Overimmunosuppression (TWO) study protocol

    Susan Dutton / Ines Rombach / Joanna Black / Paul Harden / Giovanna Lombardi / William Petchey / Kathryn Wood / Fadi Issa / Matthew Oliver Brook / Joanna Hester / Matthew James Bottomley / Seetha Abdul-Wahab / Andrew Bushell / Peter Friend

    BMJ Open, Vol 12, Iss

    a phase 2b randomised controlled single-centre trial of regulatory T cell therapy to facilitate immunosuppression reduction in living donor kidney transplant recipients

    2022  Volume 4

    Keywords Medicine ; R
    Language English
    Publishing date 2022-04-01T00:00:00Z
    Publisher BMJ Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Convergent structural features of respiratory syncytial virus neutralizing antibodies and plasticity of the site V epitope on prefusion F.

    Wayne Harshbarger / Sai Tian / Newton Wahome / Ankita Balsaraf / Deep Bhattacharya / Desheng Jiang / Ratnesh Pandey / Kunal Tungare / Kristian Friedrich / Nurjahan Mehzabeen / Marco Biancucci / Diana Chinchilla-Olszar / Corey P Mallett / Ying Huang / Zihao Wang / Matthew James Bottomley / Enrico Malito / Sumana Chandramouli

    PLoS Pathogens, Vol 16, Iss 11, p e

    2020  Volume 1008943

    Abstract: Respiratory syncytial virus (RSV) is a global public health burden for which no licensed vaccine exists. To aid vaccine development via increased understanding of the protective antibody response to RSV prefusion glycoprotein F (PreF), we performed ... ...

    Abstract Respiratory syncytial virus (RSV) is a global public health burden for which no licensed vaccine exists. To aid vaccine development via increased understanding of the protective antibody response to RSV prefusion glycoprotein F (PreF), we performed structural and functional studies using the human neutralizing antibody (nAb) RSB1. The crystal structure of PreF complexed with RSB1 reveals a conformational, pre-fusion specific site V epitope with a unique cross-protomer binding mechanism. We identify shared structural features between nAbs RSB1 and CR9501, elucidating for the first time how diverse germlines obtained from different subjects can develop convergent molecular mechanisms for recognition of the same PreF site of vulnerability. Importantly, RSB1-like nAbs were induced upon immunization with PreF in naturally-primed cattle. Together, this work reveals new details underlying the immunogenicity of site V and further supports PreF-based vaccine development efforts.
    Keywords Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2020-11-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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    Inter-library loan at ZB MED

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