4 results on '"Smith, Kenneth G. C. [0000-0003-3829-4326]"'
Number of results to display per page
Search Results
2. Age-related immune response heterogeneity to SARS-CoV-2 vaccine BNT162b2
- Author
-
Collier, Dami A., Ferreira, Isabella A. T. M., Kotagiri, Prasanti, Datir, Rawlings P., Lim, Eleanor Y., Touizer, Emma, Meng, Bo, Abdullahi, Adam, Elmer, Anne, Kingston, Nathalie, Graves, Barbara, Le Gresley, Emma, Caputo, Daniela, Bergamaschi, Laura, Smith, Kenneth G. C., Bradley, John R., Ceron-Gutierrez, Lourdes, Cortes-Acevedo, Paulina, Barcenas-Morales, Gabriela, Linterman, Michelle A., McCoy, Laura E., Davis, Chris, Thomson, Emma, McKinney, Eoin, Doffinger, Rainer, Wills, Mark, Gupta, Ravindra K., Baker, Stephen, Dougan, Gordon, Hess, Christoph, Lehner, Paul J., Lyons, Paul A., Matheson, Nicholas J., Owehand, Willem H., Saunders, Caroline, Summers, Charlotte, Thaventhiran, James E. D., Toshner, Mark, Weekes, Michael P., Maxwell, Patrick, Shaw, Ashley, Bucke, Ashlea, Calder, Jo, Canna, Laura, Domingo, Jason, Fuller, Stewart, Harris, Julie, Hewitt, Sarah, Kennet, Jane, Jose, Sherly, Kourampa, Jenny, Meadows, Anne, O’Brien, Criona, Price, Jane, Publico, Cherry, Rastall, Rebecca, Ribeiro, Carla, Rowlands, Jane, Ruffolo, Valentina, Tordesillas, Hugo, Bullman, Ben, Dunmore, Benjamin J., Fawke, Stuart, Gräf, Stefan, Hodgson, Josh, Huang, Christopher, Hunter, Kelvin, Jones, Emma, Legchenko, Ekaterina, Matara, Cecilia, Martin, Jennifer, Mescia, Federica, O’Donnell, Ciara, Pointon, Linda, Pond, Nicole, Shih, Joy, Sutcliffe, Rachel, Tilly, Tobias, Treacy, Carmen, Tong, Zhen, Wood, Jennifer, Wylot, Marta, Betancourt, Ariana, Bower, Georgie, Cossetti, Chiara, De Sa, Aloka, Epping, Madeline, Gleadall, Nick, Grenfell, Richard, Hinch, Andrew, Huhn, Oisin, Jackson, Sarah, Jarvis, Isobel, Krishna, Ben, Lewis, Daniel, Marsden, Joe, Nice, Francesca, Okecha, Georgina, Omarjee, Ommar, Perera, Marianne, Potts, Martin, Richoz, Nathan, Romashova, Veronika, Yarkoni, Natalia Savinykh, Sharma, Rahul, Stefanucci, Luca, Stephens, Jonathan, Strezlecki, Mateusz, Turner, Lori, D. D. De Bie, Eckart M., Bunclark, Katherine, Josipovic, Masa, Mackay, Michael, Michael, Alice, Rossi, Sabrina, Selvan, Mayurun, Spencer, Sarah, Yong, Cissy, Ansaripour, Ali, Mwaura, Lucy, Patterson, Caroline, Polwarth, Gary, Polgarova, Petra, Di Stefano, Giovanni, Fahey, Codie, Michel, Rachel, Bong, Sze-How, Coudert, Jerome D., Holmes, Elaine, Allison, John, Butcher, Helen, Clapham-Riley, Debbie, Dewhurst, Eleanor, Furlong, Anita, Gray, Jennifer, Ivers, Tasmin, Kasanicki, Mary, Linger, Rachel, Meloy, Sarah, Muldoon, Francesca, Ovington, Nigel, Papadia, Sofia, Phelan, Isabel, Stark, Hannah, Stirrups, Kathleen E., Townsend, Paul, Walker, Neil, Webster, Jennifer, Collier, Dami A. [0000-0001-5446-4423], Datir, Rawlings P. [0000-0003-0521-2144], Smith, Kenneth G. C. [0000-0003-3829-4326], Linterman, Michelle A. [0000-0001-6047-1996], McCoy, Laura E. [0000-0001-9503-7946], Thomson, Emma [0000-0003-1482-0889], Lyons, Paul A. [0000-0001-7035-8997], Gupta, Ravindra K. [0000-0001-9751-1808], and Apollo - University of Cambridge Repository
- Subjects
article ,13/106 ,38/39 ,631/250/2152/2153/1291 ,631/326/596/4130 ,38 - Abstract
Although two-dose mRNA vaccination provides excellent protection against SARS-CoV-2, there is little information about vaccine efficacy against variants of concern (VOC) in individuals above eighty years of age1. Here we analysed immune responses following vaccination with the BNT162b2 mRNA vaccine2 in elderly participants and younger healthcare workers. Serum neutralization and levels of binding IgG or IgA after the first vaccine dose were lower in older individuals, with a marked drop in participants over eighty years old. Sera from participants above eighty showed lower neutralization potency against the B.1.1.7 (Alpha), B.1.351 (Beta) and P.1. (Gamma) VOC than against the wild-type virus and were more likely to lack any neutralization against VOC following the first dose. However, following the second dose, neutralization against VOC was detectable regardless of age. The frequency of SARS-CoV-2 spike-specific memory B cells was higher in elderly responders (whose serum showed neutralization activity) than in non-responders after the first dose. Elderly participants showed a clear reduction in somatic hypermutation of class-switched cells. The production of interferon-γ and interleukin-2 by SARS-CoV-2 spike-specific T cells was lower in older participants, and both cytokines were secreted primarily by CD4 T cells. We conclude that the elderly are a high-risk population and that specific measures to boost vaccine responses in this population are warranted, particularly where variants of concern are circulating.
- Published
- 2021
- Full Text
- View/download PDF
3. Single-cell multi-omics analysis of the immune response in COVID-19
- Author
-
Stephenson, Emily, Reynolds, Gary, Botting, Rachel A., Calero-Nieto, Fernando J., Morgan, Michael D., Tuong, Zewen Kelvin, Bach, Karsten, Sungnak, Waradon, Worlock, Kaylee B., Yoshida, Masahiro, Kumasaka, Natsuhiko, Kania, Katarzyna, Engelbert, Justin, Olabi, Bayanne, Spegarova, Jarmila Stremenova, Wilson, Nicola K., Mende, Nicole, Jardine, Laura, Gardner, Louis C. S., Goh, Issac, Horsfall, Dave, McGrath, Jim, Webb, Simone, Mather, Michael W., Lindeboom, Rik G. H., Dann, Emma, Huang, Ni, Polanski, Krzysztof, Prigmore, Elena, Gothe, Florian, Scott, Jonathan, Payne, Rebecca P., Baker, Kenneth F., Hanrath, Aidan T., Schim Van Der Loeff, Ina C. D., Barr, Andrew S., Sanchez-Gonzalez, Amada, Bergamaschi, Laura, Mescia, Federica, Barnes, Josephine L., Kilich, Eliz, De Wilton, Angus, Saigal, Anita, Saleh, Aarash, Janes, Sam M., Smith, Claire M., Gopee, Nusayhah, Wilson, Caroline, Coupland, Paul, Coxhead, Jonathan M., Kiselev, Vladimir Yu, Van Dongen, Stijn, Bacardit, Jaume, King, Hamish W., Rostron, Anthony J., Simpson, A. John, Hambleton, Sophie, Laurenti, Elisa, Lyons, Paul A., Meyer, Kerstin B., Nikolić, Marko Z., Duncan, Christopher J. A., Teichmann, Sarah A., Clatworthy, Menna R., Marioni, John C., Göttgens, Berthold, Haniffa, Muzlifah, Baker, Stephen, Bradley, John R., Dougan, Gordon, Goodfellow, Ian G., Gupta, Ravindra K., Hess, Christoph, Kingston, Nathalie, Lehner, Paul J., Matheson, Nicholas J., Owehand, Willem H., Saunders, Caroline, Smith, Kenneth G. C., Summers, Charlotte, Thaventhiran, James E. D., Toshner, Mark, Weekes, Michael P., Bucke, Ashlea, Calder, Jo, Canna, Laura, Domingo, Jason, Elmer, Anne, Fuller, Stewart, Harris, Julie, Hewitt, Sarah, Kennet, Jane, Jose, Sherly, Kourampa, Jenny, Meadows, Anne, O’Brien, Criona, Price, Jane, Publico, Cherry, Rastall, Rebecca, Ribeiro, Carla, Rowlands, Jane, Ruffolo, Valentina, Tordesillas, Hugo, Bullman, Ben, Dunmore, Benjamin J., Fawke, Stuart, Gräf, Stefan, Hodgson, Josh, Huang, Christopher, Hunter, Kelvin, Jones, Emma, Legchenko, Ekaterina, Matara, Cecilia, Martin, Jennifer, O’Donnell, Ciara, Pointon, Linda, Pond, Nicole, Shih, Joy, Sutcliffe, Rachel, Tilly, Tobias, Treacy, Carmen, Tong, Zhen, Wood, Jennifer, Wylot, Marta, Betancourt, Ariana, Bower, Georgie, De Sa, Aloka, Epping, Madeline, Huhn, Oisin, Jackson, Sarah, Jarvis, Isobel, Marsden, Jimmy, Nice, Francesca, Okecha, Georgina, Omarjee, Ommar, Perera, Marianne, Richoz, Nathan, Sharma, Rahul, Turner, Lori, De Bie, Eckart M. D. D., Bunclark, Katherine, Josipovic, Masa, Mackay, Michael, Michael, Alice, Rossi, Sabrina, Selvan, Mayurun, Spencer, Sarah, Yong, Cissy, Ansaripour, Ali, Mwaura, Lucy, Patterson, Caroline, Polwarth, Gary, Polgarova, Petra, Stefano, Giovanni Di, Allison, John, Butcher, Helen, Caputo, Daniela, Clapham-Riley, Debbie, Dewhurst, Eleanor, Furlong, Anita, Graves, Barbara, Gray, Jennifer, Ivers, Tasmin, Kasanicki, Mary, Gresley, Emma Le, Linger, Rachel, Meloy, Sarah, Muldoon, Francesca, Ovington, Nigel, Papadia, Sofia, Phelan, Isabel, Stark, Hannah, Stirrups, Kathleen E., Townsend, Paul, Walker, Neil, Webster, Jennifer, Calero-Nieto, Fernando J. [0000-0003-3358-8253], Morgan, Michael D. [0000-0003-0757-0711], Tuong, Zewen Kelvin [0000-0002-6735-6808], Sungnak, Waradon [0000-0002-0136-4960], Yoshida, Masahiro [0000-0002-3521-5322], Kumasaka, Natsuhiko [0000-0002-3557-0375], Spegarova, Jarmila Stremenova [0000-0002-0710-9266], Wilson, Nicola K. [0000-0003-0865-7333], Mende, Nicole [0000-0002-5078-2333], Gardner, Louis C. S. [0000-0002-7200-978X], Goh, Issac [0000-0002-6397-3518], Horsfall, Dave [0000-0002-8086-812X], Webb, Simone [0000-0003-3058-8952], Mather, Michael W. [0000-0001-7972-7111], Lindeboom, Rik G. H. [0000-0002-3660-504X], Dann, Emma [0000-0002-7400-7438], Polanski, Krzysztof [0000-0002-2586-9576], Payne, Rebecca P. [0000-0002-9037-7367], Baker, Kenneth F. [0000-0002-6735-2911], Schim van der Loeff, Ina C. D. [0000-0003-1196-6196], Barr, Andrew S. [0000-0002-8084-7644], Mescia, Federica [0000-0002-2759-4027], Barnes, Josephine L. [0000-0001-9938-3176], Janes, Sam M. [0000-0002-6634-5939], Smith, Claire M. [0000-0002-8913-0009], Coupland, Paul [0000-0002-2871-3374], Bacardit, Jaume [0000-0002-2692-7205], King, Hamish W. [0000-0001-5972-8926], Rostron, Anthony J. [0000-0002-9336-1723], Simpson, A. John [0000-0003-4731-7294], Hambleton, Sophie [0000-0001-7954-3267], Laurenti, Elisa [0000-0002-9917-9092], Lyons, Paul A. [0000-0001-7035-8997], Meyer, Kerstin B. [0000-0001-5906-1498], Nikolić, Marko Z. [0000-0001-6304-6848], Smith, Kenneth G. C. [0000-0003-3829-4326], Teichmann, Sarah A. [0000-0002-6294-6366], Clatworthy, Menna R. [0000-0002-3340-9828], Marioni, John C. [0000-0001-9092-0852], Göttgens, Berthold [0000-0001-6302-5705], Haniffa, Muzlifah [0000-0002-3927-2084], and Apollo - University of Cambridge Repository
- Subjects
692/699/255/2514 ,631/208/514/1949 ,article ,631/250/232 ,631/250/254 ,631/326/596/4130 - Abstract
Funder: Lister Institute of Preventive Medicine; doi: https://doi.org/10.13039/501100001255, Funder: University College London, Birkbeck MRC Doctoral Training Programme, Funder: The Jikei University School of Medicine, Funder: Action Medical Research (GN2779), Funder: NIHR Clinical Lectureship (CL-2017-01-004), Funder: NIHR (ACF-2018-01-004) and the BMA Foundation, Funder: Chan Zuckerberg Initiative (grant 2017-174169) and from Wellcome (WT211276/Z/18/Z and Sanger core grant WT206194), Funder: UKRI Innovation/Rutherford Fund Fellowship allocated by the MRC and the UK Regenerative Medicine Platform (MR/5005579/1 to M.Z.N.). M.Z.N. and K.B.M. have been funded by the Rosetrees Trust (M944), Funder: Barbour Foundation, Funder: ERC Consolidator and EU MRG-Grammar awards, Funder: Versus Arthritis Cure Challenge Research Grant (21777), and an NIHR Research Professorship (RP-2017-08-ST2-002), Funder: European Molecular Biology Laboratory (EMBL), Analysis of human blood immune cells provides insights into the coordinated response to viral infections such as severe acute respiratory syndrome coronavirus 2, which causes coronavirus disease 2019 (COVID-19). We performed single-cell transcriptome, surface proteome and T and B lymphocyte antigen receptor analyses of over 780,000 peripheral blood mononuclear cells from a cross-sectional cohort of 130 patients with varying severities of COVID-19. We identified expansion of nonclassical monocytes expressing complement transcripts (CD16+C1QA/B/C+) that sequester platelets and were predicted to replenish the alveolar macrophage pool in COVID-19. Early, uncommitted CD34+ hematopoietic stem/progenitor cells were primed toward megakaryopoiesis, accompanied by expanded megakaryocyte-committed progenitors and increased platelet activation. Clonally expanded CD8+ T cells and an increased ratio of CD8+ effector T cells to effector memory T cells characterized severe disease, while circulating follicular helper T cells accompanied mild disease. We observed a relative loss of IgA2 in symptomatic disease despite an overall expansion of plasmablasts and plasma cells. Our study highlights the coordinated immune response that contributes to COVID-19 pathogenesis and reveals discrete cellular components that can be targeted for therapy.
- Published
- 2021
- Full Text
- View/download PDF
4. A CD8+ NK cell transcriptomic signature associated with clinical outcome in relapsing remitting multiple sclerosis
- Author
-
Kristina M. Harris, Christopher Connor, Dawn E. Smilek, Edward J. Carr, Giulia Manferrari, Kenneth G. C. Smith, Iona Cuthbertson, Eoin F. McKinney, Scott S. Zamvil, McKinney, Eoin F. [0000-0003-3516-3072], Cuthbertson, Iona [0000-0002-0245-4466], Harris, Kristina M. [0000-0002-6957-514X], Connor, Christopher [0000-0002-1761-2412], Carr, Edward J. [0000-0001-9343-4593], Zamvil, Scott S. [0000-0003-2720-9915], Smith, Kenneth G. C. [0000-0003-3829-4326], Apollo - University of Cambridge Repository, McKinney, Eoin F [0000-0003-3516-3072], Harris, Kristina M [0000-0002-6957-514X], Carr, Edward J [0000-0001-9343-4593], Zamvil, Scott S [0000-0003-2720-9915], and Smith, Kenneth GC [0000-0003-3829-4326]
- Subjects
0301 basic medicine ,Science ,Neuroimmunology ,Treatment outcome ,Cell ,General Physics and Astronomy ,CD8-Positive T-Lymphocytes ,Lymphocyte Activation ,Article ,General Biochemistry, Genetics and Molecular Biology ,38 ,Multiple sclerosis ,Transcriptome ,03 medical and health sciences ,Multiple Sclerosis, Relapsing-Remitting ,0302 clinical medicine ,immune system diseases ,Risk Factors ,medicine ,Humans ,692/617/375/1666 ,Gene Regulatory Networks ,45/91 ,HLA-G Antigens ,Multidisciplinary ,business.industry ,Extramural ,Reproducibility of Results ,General Chemistry ,medicine.disease ,nervous system diseases ,3. Good health ,Killer Cells, Natural ,631/378/371 ,Treatment Outcome ,030104 developmental biology ,medicine.anatomical_structure ,Gene Expression Regulation ,Multicenter study ,Relapsing remitting ,Immunology ,business ,030217 neurology & neurosurgery ,CD8 - Abstract
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) with the majority of cases characterised by relapsing/remitting (RRMS) attacks of neurologic dysfunction followed by variable resolution. Improving clinical outcomes in RRMS requires both a better understanding of the immunological mechanisms driving recurrent demyelination and better means of predicting future disease course to facilitate early targeted therapy. Here, we apply hypothesis-generating network transcriptomics to CD8+ cells isolated from patients in RRMS, identifying a signature reflecting expansion of a subset of CD8+ natural killer cells (NK8+) associated with favourable outcome. NK8+ are capable of regulating CD4+ T cell activation and proliferation in vitro, with reduced expression of HLA-G binding inhibitory receptors and consequent reduced sensitivity to HLA-G-mediated suppression. We identify surrogate markers of the NK8+ signature in peripheral blood leucocytes and validate their association with clinical outcome in an independent cohort, suggesting their measurement may facilitate early, targeted therapy in RRMS., A better understanding of how multiple sclerosis (MS) can relapse and remit is needed for the identification of biomarkers and better therapeutics. Here the authors identify a CD8 + NK cell population in patients with relapsing remitting MS and validate its association with clinical outcome.
- Published
- 2021
- Full Text
- View/download PDF
Catalog
Books, media, physical & digital resources
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.