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3. Immunogenicity of third dose COVID-19 vaccine strategies in patients who are immunocompromised with suboptimal immunity following two doses (OCTAVE-DUO): an open-label, multicentre, randomised, controlled, phase 3 trial

Author

Beesley, Richard, Churchill, Vicky, Insch, Elspeth, Loughton, Holly, MacDonald, Eilean, Lax, Siân, Lowe, Faye, Magwaro, Sophia, Gradwell, Mark, Kinsella, Francesca, Rolfe, Hayley, McIntyre, Stacey, Mortimer, Paige, Al-Taei, Saly, Tadros, Susan, Workman, Sarita, Arnott, Maxine, Brock, James, Melville, Andrew, Najm, Aurelie, Rutherford, Matthew, Sunzini, Flavia, Herman, Lou S, Hobbs, Agnieszka, Ragno, Martina, Wu, Mary Y, Selby, Rachael, Clay, Jennifer, Hutchison, Clare, Lown, Robert, Lwin, May N, Meardon, Naomi, Kelleher, Peter, Lightstone, Liz, Walters, Thomas, Denyer, Jayne, Ibrahim, Rahima, Gleeson, Sarah, Martin, Paul, McAdoo, Stephen, Baker, Helena, Horswill, Sarah, Parungao, Nina, Saich, Stephen, Cullinane, James, Irwin, Sophie, Klenerman, Paul, Marjot, Thomas, Chakraverty, Ronjon, Holroyd, Christopher, Kavi, Janki, Trown, Doreen, Babbage, Gavin, Chackathayil, Julia, Faria, Patricia, Ingham, Karen, Miah, Murad, Miranda, Mauro, O'Reilly, Nicola, Smith, Callie, Driver, Kimberley, Gauntlett, Kaylee, Farthing, Andrew, Rundell, Suzann, Smith, Emily, Tong, Andrew, Woolcock, Kieran, Hanke, Daniel, Laidlaw, Stephen, Malik, Zainab, Nguyen, Dung, Provine, Nicholas, Tipton, Tom, Walker, Victoria, Goodyear, Carl S, Patel, Amit, Barnes, Eleanor, Willicombe, Michelle, Siebert, Stefan, de Silva, Thushan I, Snowden, John A, Lim, Sean H, Bowden, Sarah J, Billingham, Lucinda, Richter, Alex, Carroll, Miles, Carr, Edward J, Beale, Rupert, Rea, Daniel, Parry, Helen, Pirrie, Sarah, Lim, Zixiang, Satsangi, Jack, Dunachie, Susanna J, Cook, Gordon, Miller, Paul, Basu, Neil, Gilmour, Ashley, Hodgkins, Anne-Marie, Evans, Lili, Hughes, Ana, Longet, Stephanie, Meacham, Georgina, Yong, Kwee L, A'Hearne, Matthew J, Koh, Mickey B C, Burns, Siobhan O, Orchard, Kim, Paterson, Caron, McIlroy, Graham, Murray, Sam M, Thomson, Tina, Dimitriadis, Stavros, Goulston, Lyndsey, Miller, Samantha, Keillor, Victoria, Prendecki, Maria, Thomas, David, Kirkham, Amanda, McInnes, Iain B, and Kearns, Pamela

Published
2024
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5. Immune responses and clinical outcomes after COVID-19 vaccination in patients with liver disease and liver transplant recipients

Author

Murray, Sam M., Pose, Elisa, Wittner, Melanie, Londoño, Maria-Carlota, Schaub, Golda, Cook, Jonathan, Dimitriadis, Stavros, Meacham, Georgina, Irwin, Sophie, Lim, Zixiang, Duengelhoef, Paul, Sterneck, Martina, Lohse, Ansgar W., Perez, Valeria, Trivedi, Palak, Bhandal, Khush, Mullish, Benjamin H., Manousou, Pinelopi, Provine, Nicholas M., Avitabile, Emma, Carroll, Miles, Tipton, Tom, Healy, Saoirse, Burra, Patrizia, Klenerman, Paul, Dunachie, Susanna, Kronsteiner, Barbara, Maciola, Agnieszka Katarzyna, Pasqual, Giulia, Hernandez-Gea, Virginia, Garcia-Pagan, Juan Carlos, Lampertico, Pietro, Iavarone, Massimo, Gines, Pere, Lütgehetmann, Marc, Schulze zur Wiesch, Julian, Russo, Francesco Paolo, Barnes, Eleanor, and Marjot, Thomas

Published
2024
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6. A conserved population of MHC II-restricted, innate-like, commensal-reactive T cells in the gut of humans and mice

Author

Hackstein, Carl-Philipp, Costigan, Dana, Drexhage, Linnea, Pearson, Claire, Bullers, Samuel, Ilott, Nicholas, Akther, Hossain Delowar, Gu, Yisu, FitzPatrick, Michael E. B., Harrison, Oliver J., Garner, Lucy C., Mann, Elizabeth H., Pandey, Sumeet, Friedrich, Matthias, Provine, Nicholas M., Uhlig, Holm H., Marchi, Emanuele, Powrie, Fiona, Klenerman, Paul, and Thornton, Emily E.

Published
2022
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7. Immunogenicity of third dose COVID-19 vaccine strategies in patients who are immunocompromised with suboptimal immunity following two doses (OCTAVE-DUO): an open-label, multicentre, randomised, controlled, phase 3 trial

Author

Goodyear, Carl S, primary, Patel, Amit, additional, Barnes, Eleanor, additional, Willicombe, Michelle, additional, Siebert, Stefan, additional, de Silva, Thushan I, additional, Snowden, John A, additional, Lim, Sean H, additional, Bowden, Sarah J, additional, Billingham, Lucinda, additional, Richter, Alex, additional, Carroll, Miles, additional, Carr, Edward J, additional, Beale, Rupert, additional, Rea, Daniel, additional, Parry, Helen, additional, Pirrie, Sarah, additional, Lim, Zixiang, additional, Satsangi, Jack, additional, Dunachie, Susanna J, additional, Cook, Gordon, additional, Miller, Paul, additional, Basu, Neil, additional, Gilmour, Ashley, additional, Hodgkins, Anne-Marie, additional, Evans, Lili, additional, Hughes, Ana, additional, Longet, Stephanie, additional, Meacham, Georgina, additional, Yong, Kwee L, additional, A'Hearne, Matthew J, additional, Koh, Mickey B C, additional, Burns, Siobhan O, additional, Orchard, Kim, additional, Paterson, Caron, additional, McIlroy, Graham, additional, Murray, Sam M, additional, Thomson, Tina, additional, Dimitriadis, Stavros, additional, Goulston, Lyndsey, additional, Miller, Samantha, additional, Keillor, Victoria, additional, Prendecki, Maria, additional, Thomas, David, additional, Kirkham, Amanda, additional, McInnes, Iain B, additional, Kearns, Pamela, additional, Beesley, Richard, additional, Churchill, Vicky, additional, Insch, Elspeth, additional, Loughton, Holly, additional, MacDonald, Eilean, additional, Lax, Siân, additional, Lowe, Faye, additional, Magwaro, Sophia, additional, Gradwell, Mark, additional, Kinsella, Francesca, additional, Rolfe, Hayley, additional, McIntyre, Stacey, additional, Mortimer, Paige, additional, Al-Taei, Saly, additional, Tadros, Susan, additional, Workman, Sarita, additional, Arnott, Maxine, additional, Brock, James, additional, Melville, Andrew, additional, Najm, Aurelie, additional, Rutherford, Matthew, additional, Sunzini, Flavia, additional, Herman, Lou S, additional, Hobbs, Agnieszka, additional, Ragno, Martina, additional, Wu, Mary Y, additional, Selby, Rachael, additional, Clay, Jennifer, additional, Hutchison, Clare, additional, Lown, Robert, additional, Lwin, May N, additional, Meardon, Naomi, additional, Kelleher, Peter, additional, Lightstone, Liz, additional, Walters, Thomas, additional, Denyer, Jayne, additional, Ibrahim, Rahima, additional, Gleeson, Sarah, additional, Martin, Paul, additional, McAdoo, Stephen, additional, Baker, Helena, additional, Horswill, Sarah, additional, Parungao, Nina, additional, Saich, Stephen, additional, Cullinane, James, additional, Irwin, Sophie, additional, Klenerman, Paul, additional, Marjot, Thomas, additional, Chakraverty, Ronjon, additional, Holroyd, Christopher, additional, Kavi, Janki, additional, Trown, Doreen, additional, Babbage, Gavin, additional, Chackathayil, Julia, additional, Faria, Patricia, additional, Ingham, Karen, additional, Miah, Murad, additional, Miranda, Mauro, additional, O'Reilly, Nicola, additional, Smith, Callie, additional, Driver, Kimberley, additional, Gauntlett, Kaylee, additional, Farthing, Andrew, additional, Rundell, Suzann, additional, Smith, Emily, additional, Tong, Andrew, additional, Woolcock, Kieran, additional, Hanke, Daniel, additional, Laidlaw, Stephen, additional, Malik, Zainab, additional, Nguyen, Dung, additional, Provine, Nicholas, additional, Tipton, Tom, additional, and Walker, Victoria, additional

Published
2024
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8. Neurodegenerative fluid biomarkers are enriched in human cervical lymph nodes

Author

Al-Diwani, Adam, primary, Provine, Nicholas, additional, Murchison, Andrew, additional, Laban, Rhiannon, additional, Swann, Owen, additional, Koychev, Ivan, additional, Sheerin, Fintan, additional, Da Mesquita, Sandro, additional, Heslegrave, Amanda, additional, Zetterberg, Henrik, additional, Klenerman, Paul, additional, and Irani, Sarosh, additional

Published
2024
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10. T cell and antibody responses induced by a single dose of ChAdOx1 nCoV-19 (AZD1222) vaccine in a phase 1/2 clinical trial

Author

Ewer, Katie J., Barrett, Jordan R., Belij-Rammerstorfer, Sandra, Sharpe, Hannah, Makinson, Rebecca, Morter, Richard, Flaxman, Amy, Alderson, Jennifer, Bittaye, Mustapha, Dold, Christina, Provine, Nicholas M., Aboagye, Jeremy, Fowler, Jamie, Silk, Sarah E., Aley, Parvinder K., Bellamy, Duncan, and Wright, Daniel

Subjects
T cells -- Physiological aspects, Biological sciences, Health
Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus Disease 2019 (COVID-19), has caused a global pandemic, and safe, effective vaccines are urgently needed.sup.1. Strong, Th1-skewed T cell responses can drive protective humoral and cell-mediated immune responses.sup.2 and might reduce the potential for disease enhancement.sup.3. Cytotoxic T cells clear virus-infected host cells and contribute to control of infection.sup.4. Studies of patients infected with SARS-CoV-2 have suggested a protective role for both humoral and cell-mediated immune responses in recovery from COVID-19 (refs. .sup.5,6). ChAdOx1 nCoV-19 (AZD1222) is a candidate SARS-CoV-2 vaccine comprising a replication-deficient simian adenovirus expressing full-length SARS-CoV-2 spike protein. We recently reported preliminary safety and immunogenicity data from a phase 1/2 trial of the ChAdOx1 nCoV-19 vaccine (NCT04400838).sup.7 given as either a one- or two-dose regimen. The vaccine was tolerated, with induction of neutralizing antibodies and antigen-specific T cells against the SARS-CoV-2 spike protein. Here we describe, in detail, exploratory analyses of the immune responses in adults, aged 18-55 years, up to 8 weeks after vaccination with a single dose of ChAdOx1 nCoV-19 in this trial, demonstrating an induction of a Th1-biased response characterized by interferon-[gamma] and tumor necrosis factor-[alpha] cytokine secretion by CD4.sup.+ T cells and antibody production predominantly of IgG1 and IgG3 subclasses. CD8.sup.+ T cells, of monofunctional, polyfunctional and cytotoxic phenotypes, were also induced. Taken together, these results suggest a favorable immune profile induced by ChAdOx1 nCoV-19 vaccine, supporting the progression of this vaccine candidate to ongoing phase 2/3 trials to assess vaccine efficacy. A single dose of the ChAdOx1 nCoV-19 vaccine elicits antibodies and cytokine-producing T cells that might help control or prevent SARS-CoV-2 infection., Author(s): Katie J. Ewer [sup.1] , Jordan R. Barrett [sup.1] , Sandra Belij-Rammerstorfer [sup.1] , Hannah Sharpe [sup.1] , Rebecca Makinson [sup.1] , Richard Morter [sup.1] , Amy Flaxman [sup.1] [...]

Published
2021
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11. Fine needle aspiration of human lymph nodes reveals cell populations and soluble interactors pivotal to immunological priming.

Author

Provine, Nicholas M., Al‐Diwani, Adam, Agarwal, Devika, Dooley, Kyla, Heslington, Amelia, Murchison, Andrew G., Garner, Lucy C., Sheerin, Fintan, Klenerman, Paul, and Irani, Sarosh R.

Subjects
NEEDLE biopsy, LYMPH nodes, CELL populations, GERMINAL centers, TRANSCRIPTOMES, LUPUS nephritis, LYMPHADENITIS
Abstract

Lymph node (LN) fine needle aspiration (LN FNA) represents a powerful technique for minimally invasive sampling of human LNs in vivo and has been used effectively to directly study aspects of the human germinal center response. However, systematic deep phenotyping of the cellular populations and cell‐free proteins recovered by LN FNA has not been performed. Thus, we studied human cervical LN FNAs as a proof‐of‐concept and used single‐cell RNA‐sequencing and proteomic analysis to benchmark this compartment, define the purity of LN FNA material, and facilitate future studies in this immunologically pivotal environment. Our data provide evidence that LN FNAs contain bone‐fide LN‐resident innate immune populations, with minimal contamination of blood material. Examination of these populations reveals unique biology not predictable from equivalent blood‐derived populations. LN FNA supernatants represent a specific source of lymph‐ and lymph node‐derived proteins, and can, aided by transcriptomics, identify likely receptor–ligand interactions. This represents the first description of the types and abundance of immune cell populations and cell‐free proteins that can be efficiently studied by LN FNA. These findings are of broad utility for understanding LN physiology in health and disease, including infectious or autoimmune perturbations, and in the case of cervical nodes, neuroscience. [ABSTRACT FROM AUTHOR]

Published
2024
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12. An Interpretable Classification Model Using Gluten-Specific TCR Sequences Shows Diagnostic Potential in Coeliac Disease

Author

Fowler, Anna, primary, FitzPatrick, Michael, additional, Shanmugarasa, Aberami, additional, Ibrahim, Amro Sayed Fadel, additional, Kockelbergh, Hannah, additional, Yang, Han-Chieh, additional, Williams-Walker, Amelia, additional, Luu Hoang, Kim Ngan, additional, Evans, Shelley, additional, Provine, Nicholas, additional, Klenerman, Paul, additional, and Soilleux, Elizabeth J., additional

Published
2023
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13. Human MAIT Cell Activation In Vitro

Author

Hagel, Joachim P., primary, Garner, Lucy C., additional, Bilton, Matthew, additional, Mehta, Hema, additional, Leng, Tianqi, additional, Hackstein, Carl-Philipp, additional, Phalora, Prabhjeet, additional, Amini, Ali, additional, Akther, Hossain D., additional, Provine, Nicholas M., additional, Edmans, Matthew, additional, Willberg, Christian B., additional, and Klenerman, Paul, additional

Published
2019
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14. Development of novel replication-defective lymphocytic choriomeningitis virus vectors expressing SIV antigens

Author

Penaloza MacMaster, Pablo, Shields, Jennifer L., Alayo, Quazim A., Cabral, Crystal, Jimenez, Jessica, Mondesir, Jade, Chandrashekar, Abishek, Cabral, Joseph M., Lim, Matthew, Iampietro, M. Justin, Provine, Nicholas M., Bricault, Christine A., Seaman, Michael, Orlinger, Klaus, Aspoeck, Andreas, Fuhrmann, Gerhard, Lilja, Anders E., Monath, Thomas, Mangeat, Bastien, Pinschewer, Daniel D., and Barouch, Dan H.

Published
2017
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19. Vaccine-elicited CD4 T cells induce immunopathology after chronic LCMV infection

Author

Penaloza-MacMaster, Pablo, Barber, Daniel L., Wherry, E. John, Provine, Nicholas M., Teigler, Jeffrey E., Parenteau, Lily, Blackmore, Stephen, Borducchi, Erica N., Larocca, Rafael A., Yates, Kathleen B., Shen, Hao, Haining, W. Nicholas, Sommerstein, Rami, Pinschewer, Daniel D., Ahmed, Rafi, and Barouch, Dan H.

Published
2015

21. A conserved population of MHC II-restricted, innate-like, commensal-reactive T cells in the gut of humans and mice

Author

Hackstein, Carl-Philipp, primary, Costigan, Dana, additional, Drexhage, Linnea, additional, Pearson, Claire, additional, Bullers, Samuel, additional, Ilott, Nicholas, additional, Akther, Hossain Delowar, additional, Gu, Yisu, additional, FitzPatrick, Michael E.B., additional, Harrison, Oliver J., additional, Garner, Lucy C., additional, Mann, Elizabeth H., additional, Pandey, Sumeet, additional, Friedrich, Matthias, additional, Provine, Nicholas M., additional, Uhlig, Holm, additional, Marchi, Emanuele, additional, Powrie, Fiona, additional, Klenerman, Paul, additional, and Thornton, Emily E., additional

Published
2022
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22. Adenovirus vector and mRNA vaccines: Mechanisms regulating their immunogenicity.

Author

Provine, Nicholas M. and Klenerman, Paul

Subjects
IMMUNE response, ADENOVIRUSES, VACCINES, MESSENGER RNA, COVID-19 pandemic
Abstract

Replication‐incompetent adenovirus (Ad) vector and mRNA‐lipid nanoparticle (LNP) constructs represent two modular vaccine platforms that have attracted substantial interest over the past two decades. Due to the COVID‐19 pandemic and the rapid development of multiple successful vaccines based on these technologies, there is now clear real‐world evidence of the utility and efficacy of these platforms. Considerable optimization and refinement efforts underpin the successful application of these technologies. Despite this, our understanding of the specific pathways and processes engaged by these vaccines to stimulate the immune response remains incomplete. This review will synthesize our current knowledge of the specific mechanisms by which CD8+ T cell and antibody responses are induced by each of these vaccine platforms, and how this can be impacted by specific vaccine construction techniques. Key gaps in our knowledge are also highlighted, which can hopefully focus future studies. [ABSTRACT FROM AUTHOR]

Published
2023
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23. Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses

Author

McNaughton, Anna L, Paton, Robert S, Edmans, Matthew, Youngs, Jonathan, Wellens, Judith, Phalora, Prabhjeet, Fyfe, Alex, Belij-Rammerstorfer, Sandra, Bolton, Jai S, Ball, Jonathan, Carnell, George W, Dejnirattisai, Wanwisa, Dold, Christina, Eyre, David W, Hopkins, Philip, Howarth, Alison, Kooblall, Kreepa, Klim, Hannah, Leaver, Susannah, Lee, Lian Ni, López-Camacho, César, Lumley, Sheila F, Macallan, Derek C, Mentzer, Alexander J, Provine, Nicholas M, Ratcliff, Jeremy, Slon-Compos, Jose, Skelly, Donal, Stolle, Lucas, Supasa, Piyada, Temperton, Nigel, Walker, Chris, Wang, Beibei, Wyncoll, Duncan, Oxford Protective T Cell Immunology for COVID-19 (OPTIC) consortium, Scottish National Blood Transfusion Service (SNBTS) consortium, Simmonds, Peter, Lambe, Teresa, Baillie, John Kenneth, Semple, Malcolm G, Openshaw, Peter Jm, International Severe Acute Respiratory and emerging Infection Consortium Coronavirus Clinical Characterisation Consortium (ISARIC4C) investigators, Obolski, Uri, Turner, Marc, Carroll, Miles, Mongkolsapaya, Juthathip, Screaton, Gavin, Kennedy, Stephen H, Jarvis, Lisa, Barnes, Eleanor, Dunachie, Susanna, Lourenço, José, Matthews, Philippa C, Bicanic, Tihana, Klenerman, Paul, Gupta, Sunetra, Thompson, Craig P, Carnell, George [0000-0001-8875-0989], and Apollo - University of Cambridge Repository

Subjects
Infectious disease, Epitopes, SARS-CoV-2, FOS: Clinical medicine, Adaptive immunity, Immunology, Antibody Formation, Spike Glycoprotein, Coronavirus, COVID-19, Humans, Imprinting, Antibodies, Viral
Abstract

The role of immune responses to previously seen endemic coronavirus epitopes in severe acute respiratory coronavirus 2 (SARS-CoV-2) infection and disease progression has not yet been determined. Here, we show that a key characteristic of fatal outcomes with coronavirus disease 2019 (COVID-19) is that the immune response to the SARS-CoV-2 spike protein is enriched for antibodies directed against epitopes shared with endemic beta-coronaviruses and has a lower proportion of antibodies targeting the more protective variable regions of the spike. The magnitude of antibody responses to the SARS-CoV-2 full-length spike protein, its domains and subunits, and the SARS-CoV-2 nucleocapsid also correlated strongly with responses to the endemic beta-coronavirus spike proteins in individuals admitted to an intensive care unit (ICU) with fatal COVID-19 outcomes, but not in individuals with nonfatal outcomes. This correlation was found to be due to the antibody response directed at the S2 subunit of the SARS-CoV-2 spike protein, which has the highest degree of conservation between the beta-coronavirus spike proteins. Intriguingly, antibody responses to the less cross-reactive SARS-CoV-2 nucleocapsid were not significantly different in individuals who were admitted to an ICU with fatal and nonfatal outcomes, suggesting an antibody profile in individuals with fatal outcomes consistent with an "original antigenic sin" type response.

Published
2022
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24. Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses

Author

McNaughton, Anna L., primary, Paton, Robert S., additional, Edmans, Matthew, additional, Youngs, Jonathan, additional, Wellens, Judith, additional, Phalora, Prabhjeet, additional, Fyfe, Alex, additional, Belij-Rammerstorfer, Sandra, additional, Bolton, Jai S., additional, Ball, Jonathan, additional, Carnell, George W., additional, Dejnirattisai, Wanwisa, additional, Dold, Christina, additional, Eyre, David W., additional, Hopkins, Philip, additional, Howarth, Alison, additional, Kooblall, Kreepa, additional, Klim, Hannah, additional, Leaver, Susannah, additional, Lee, Lian Ni, additional, López-Camacho, César, additional, Lumley, Sheila F., additional, Macallan, Derek C., additional, Mentzer, Alexander J., additional, Provine, Nicholas M., additional, Ratcliff, Jeremy, additional, Slon-Compos, Jose, additional, Skelly, Donal, additional, Stolle, Lucas, additional, Supasa, Piyada, additional, Temperton, Nigel, additional, Walker, Chris, additional, Wang, Beibei, additional, Wyncoll, Duncan, additional, Simmonds, Peter, additional, Lambe, Teresa, additional, Baillie, John Kenneth, additional, Semple, Malcolm G., additional, Openshaw, Peter J.M., additional, Obolski, Uri, additional, Turner, Marc, additional, Carroll, Miles, additional, Mongkolsapaya, Juthathip, additional, Screaton, Gavin, additional, Kennedy, Stephen H., additional, Jarvis, Lisa, additional, Barnes, Eleanor, additional, Dunachie, Susanna, additional, Lourenço, José, additional, Matthews, Philippa C., additional, Bicanic, Tihana, additional, Klenerman, Paul, additional, Gupta, Sunetra, additional, and Thompson, Craig P., additional

Published
2022
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25. Characterising the early inflammatory landscape of primary sclerosing cholangitis

Author

Dendrou, Calli, primary, Lynch, Kate, additional, Curion, Fabiola, additional, Rich-Griffin, Charlotte, additional, Yeung, Hing-Yuen, additional, Provine, Nicholas, additional, Ilott, Nicholas, additional, Ferry, Helen, additional, Fryer, Eve, additional, Uhlig, Holm, additional, Chapman, Roger W.G., additional, Keshav, Satish, additional, and Klenerman, Paul, additional

Published
2022
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26. Evaluation of perturbed iron-homeostasis in a prospective cohort of patients with COVID-19

Author

Frost, Joe N., primary, Hamilton, Fergus, additional, Arnold, David, additional, Elvers, Karen T., additional, Shah, Akshay, additional, Armitage, Andrew E., additional, Milne, Alice, additional, McKernon, Jorgen, additional, Attwood, Marie, additional, Chen, Yi-Ling, additional, Xue, Luzheng, additional, Youngs, Jonathan, additional, Provine, Nicholas M., additional, Bicanic, Tihana, additional, Klenerman, Paul, additional, Drakesmith, Hal, additional, and Ghazal, Peter, additional

Published
2022
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27. Fatal COVID-19 outcomes are associated with an antibody response targeting epitopes shared with endemic coronaviruses

Author

McNaughton, Anna L., Paton, Robert S., Edmans, Matthew, Youngs, Jonathan C.W., Wellens, Judith, Phalora, Prabhjeet, Fyfe, Alex, Belij-Rammerstorfer, Sandra, Bolton, Jai S., Ball, Jonathan, Carnell, George W., Dejnirattisai, Wanwisa, Dold, Christina, Eyre, David W., Hopkins, Philip, Howarth, Alison, Kooblall, Kreepa, Klim, Hannah, Leaver, Susannah, Lee, Lian N., López-Camacho, César, Lumley, Sheila F., Macallan, Derek C., Mentzer, Alexander J., Provine, Nicholas M., Ratcliff, Jeremy, Slon-Campos, Jose L., Skelly, Donal T., Stolle, Lucas B., Supasa, Piyada, Temperton, Nigel J., Walker, Chris, Wang, Beibei, Wyncoll, Duncan, Simmonds, Peter, Lambe, Teresa, Ballie, John K., Semple, Malcolm G., Openshaw, Peter J.M., Obolski, Uri, Turner, Marc, Carroll, Miles, Mongkolsapaya, Juthathip, Screaton, Gavin, Kennedy, Stephen H., Jarvis, Lisa M., Barnes, Eleanor, Dunachie, Susanna, Lourenço, José, Matthews, Philippa C., Bicanic, Tihana, Klenerman, Paul, Gupta, Sunetra, Thompson, Craig P., McNaughton, Anna L., Paton, Robert S., Edmans, Matthew, Youngs, Jonathan C.W., Wellens, Judith, Phalora, Prabhjeet, Fyfe, Alex, Belij-Rammerstorfer, Sandra, Bolton, Jai S., Ball, Jonathan, Carnell, George W., Dejnirattisai, Wanwisa, Dold, Christina, Eyre, David W., Hopkins, Philip, Howarth, Alison, Kooblall, Kreepa, Klim, Hannah, Leaver, Susannah, Lee, Lian N., López-Camacho, César, Lumley, Sheila F., Macallan, Derek C., Mentzer, Alexander J., Provine, Nicholas M., Ratcliff, Jeremy, Slon-Campos, Jose L., Skelly, Donal T., Stolle, Lucas B., Supasa, Piyada, Temperton, Nigel J., Walker, Chris, Wang, Beibei, Wyncoll, Duncan, Simmonds, Peter, Lambe, Teresa, Ballie, John K., Semple, Malcolm G., Openshaw, Peter J.M., Obolski, Uri, Turner, Marc, Carroll, Miles, Mongkolsapaya, Juthathip, Screaton, Gavin, Kennedy, Stephen H., Jarvis, Lisa M., Barnes, Eleanor, Dunachie, Susanna, Lourenço, José, Matthews, Philippa C., Bicanic, Tihana, Klenerman, Paul, Gupta, Sunetra, and Thompson, Craig P.

Abstract

The role of immune responses to previously seen endemic coronavirus epitopes in severe acute respiratory coronavirus 2 (SARS-CoV-2) infection and disease progression has not yet been determined. Here, we show that a key characteristic of fatal coronavirus disease (COVID-19) outcomes is that the immune response to the SARS-CoV-2 spike protein is enriched for antibodies directed against epitopes shared with endemic beta-coronaviruses, and has a lower proportion of antibodies targeting the more protective variable regions of the spike. The magnitude of antibody responses to the SARS-CoV-2 full-length spike protein, its domains and subunits, and the SARS-CoV-2 nucleocapsid also correlated strongly with responses to the endemic beta-coronavirus spike proteins in individuals admitted to intensive care units (ICU) with fatal COVID-19 outcomes, but not in individuals with non-fatal outcomes. This correlation was found to be due to the antibody response directed at the S2 subunit of the SARS-CoV-2 spike protein, which has the highest degree of conservation between the beta-coronavirus spike proteins. Intriguingly, antibody responses to the less cross-reactive SARS-CoV-2 nucleocapsid were not significantly different in individuals who were admitted to ICU with fatal and non-fatal outcomes, suggesting an antibody profile in individuals with fatal outcomes consistent with an original antigenic sin type-response.

Published
2022

28. CMV-associated T cell and NK cell terminal differentiation does not affect immunogenicity of ChAdOx1 vaccination

Author

Sharpe, Hannah R., primary, Provine, Nicholas M., additional, Bowyer, Georgina S., additional, Moreira Folegatti, Pedro, additional, Belij-Rammerstorfer, Sandra, additional, Flaxman, Amy, additional, Makinson, Rebecca, additional, Hill, Adrian V.S., additional, Ewer, Katie J., additional, Pollard, Andrew J., additional, Klenerman, Paul, additional, Gilbert, Sarah, additional, and Lambe, Teresa, additional

Published
2022
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30. Adenovirus vectors activate Vδ2 + γδT cells in a type I interferon‐, TNF‐, and IL‐18‐dependent manner

Author

Provine, Nicholas M., primary, Amini, Ali, additional, Garner, Lucy C., additional, FitzPatrick, Michael E.B., additional, Dold, Christina, additional, Silva Reyes, Laura, additional, Chinnakannan, Senthil, additional, Oguti, Blanche, additional, Raymond, Meriel, additional, Troise, Fulvia, additional, Capone, Stefania, additional, Folgori, Antonella, additional, Barnes, Eleanor, additional, Rollier, Christine S., additional, Pollard, Andrew J., additional, and Klenerman, Paul, additional

Published
2022
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31. T-cell and antibody responses to first BNT162b2 vaccine dose in previously infected and SARS-CoV-2-naive UK health-care workers: a multicentre prospective cohort study

Author

Angyal, Adrienn, primary, Longet, Stephanie, additional, Moore, Shona C, additional, Payne, Rebecca P, additional, Harding, Adam, additional, Tipton, Tom, additional, Rongkard, Patpong, additional, Ali, Mohammad, additional, Hering, Luisa M, additional, Meardon, Naomi, additional, Austin, James, additional, Brown, Rebecca, additional, Skelly, Donal, additional, Gillson, Natalie, additional, Dobson, Sue L, additional, Cross, Andrew, additional, Sandhar, Gurjinder, additional, Kilby, Jonathan A, additional, Tyerman, Jessica K, additional, Nicols, Alexander R, additional, Spegarova, Jarmila S, additional, Mehta, Hema, additional, Hornsby, Hailey, additional, Whitham, Rachel, additional, Conlon, Christopher P, additional, Jeffery, Katie, additional, Goulder, Philip, additional, Frater, John, additional, Dold, Christina, additional, Pace, Matthew, additional, Ogbe, Ane, additional, Brown, Helen, additional, Ansari, M Azim, additional, Adland, Emily, additional, Brown, Anthony, additional, Chand, Meera, additional, Shields, Adrian, additional, Matthews, Philippa C, additional, Hopkins, Susan, additional, Hall, Victoria, additional, James, William, additional, Rowland-Jones, Sarah L, additional, Klenerman, Paul, additional, Dunachie, Susanna, additional, Richter, Alex, additional, Duncan, Christopher J A, additional, Barnes, Eleanor, additional, Carroll, Miles, additional, Turtle, Lance, additional, de Silva, Thushan I, additional, Watson, Adam, additional, Angyal, Adrienn, additional, Alhussni, Ahmed, additional, Nicols, Alexander, additional, Deeks, Alexandra, additional, Webb-Bridges, Alice, additional, Jämsén, Anni, additional, Chawla, Anu, additional, Duncan, Christopher, additional, Conlon, Christopher, additional, O'Donnell, Denise, additional, Weeks, Esme, additional, Abuelgasim, Hibatullah, additional, Xiao, Huiyuan, additional, Spegarova, Jarmila, additional, Holmes, Jennifer, additional, Haworth, Jenny, additional, Tyerman, Jessica, additional, Kilby, Jonathan, additional, Cutteridge, Joseph, additional, Lillie, Katy, additional, Romaniuk, Leigh, additional, Denly, Lucy, additional, Hering, Luisa, additional, Ansari, M. Azim, additional, Kasanyinga, Mwila, additional, Matthews, Philippa, additional, Payne, Rebecca, additional, Wilson, Robert, additional, Rowland-Jones, Sarah, additional, Thomas, Sarah, additional, Moore, Shona, additional, Gardiner, Siobhan, additional, Tucker, Stephanie, additional, Dobson, Sue, additional, Adlou, Syed, additional, de Silva, Thushan, additional, Lawrie, Allan, additional, Smith, Nikki, additional, Turton, Helena, additional, Zawia, Amira, additional, Bayley, Martin, additional, Fairman, Alex, additional, Harrington, Kate, additional, Kirk, Rosemary, additional, Marsh, Louise, additional, Watson, Lisa, additional, Wood, Steven, additional, Diffey, Benjamin, additional, Jones, Chris, additional, Lett, Lauren, additional, Platt, Gareth, additional, Subramaniam, Krishanthi, additional, Wootton, Daniel, additional, Payne, Brendan, additional, Hambleton, Sophie, additional, Kelly, Sinead, additional, Marston, Judith, additional, Poolan, Sonia, additional, Turner, Dianne, additional, Haniffa, Muzlifah, additional, Stephenson, Emily, additional, Adele, Sandra, additional, Akhter, Hossain Delowar, additional, Chinnakannan, Senthil, additional, de Lara, Catherine, additional, Donnison, Timothy, additional, Hackstein, Carl-Philipp, additional, Lee, Lian, additional, Lim, Nicholas, additional, Malone, Tom, additional, Phillips, Eloise, additional, Ramamurthy, Narayan, additional, Robinson, Nichola, additional, Sampson, Oliver, additional, Eyre, David, additional, Simmons, Beatrice, additional, Stafford, Lizzie, additional, Mentzer, Alexander, additional, Amini, Ali, additional, Arancibia-Cárcamo, Carolina, additional, Provine, Nicholas, additional, Travis, Simon, additional, Dimitriadis, Stavros, additional, Johnson, Sile, additional, Foulkes, Sarah, additional, Khawam, Jameel, additional, Wellington, Edgar, additional, Gilbert-Jaramillo, Javier, additional, Knight, Michael, additional, Dupont, Maeva, additional, Horner, Emily, additional, Thaventhiran, James, additional, and Chalk, Jeremy, additional

Published
2022
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32. Immunogenicity of standard and extended dosing intervals of BNT162b2 mRNA vaccine

Author

Payne, Rebecca P., primary, Longet, Stephanie, additional, Austin, James A., additional, Skelly, Donal T., additional, Dejnirattisai, Wanwisa, additional, Adele, Sandra, additional, Meardon, Naomi, additional, Faustini, Sian, additional, Al-Taei, Saly, additional, Moore, Shona C., additional, Tipton, Tom, additional, Hering, Luisa M., additional, Angyal, Adrienn, additional, Brown, Rebecca, additional, Nicols, Alexander R., additional, Gillson, Natalie, additional, Dobson, Susan L., additional, Amini, Ali, additional, Supasa, Piyada, additional, Cross, Andrew, additional, Bridges-Webb, Alice, additional, Reyes, Laura Silva, additional, Linder, Aline, additional, Sandhar, Gurjinder, additional, Kilby, Jonathan A., additional, Tyerman, Jessica K., additional, Altmann, Thomas, additional, Hornsby, Hailey, additional, Whitham, Rachel, additional, Phillips, Eloise, additional, Malone, Tom, additional, Hargreaves, Alexander, additional, Shields, Adrian, additional, Saei, Ayoub, additional, Foulkes, Sarah, additional, Stafford, Lizzie, additional, Johnson, Sile, additional, Wootton, Daniel G., additional, Conlon, Christopher P., additional, Jeffery, Katie, additional, Matthews, Philippa C., additional, Frater, John, additional, Deeks, Alexandra S., additional, Pollard, Andrew J., additional, Brown, Anthony, additional, Rowland-Jones, Sarah L., additional, Mongkolsapaya, Juthathip, additional, Barnes, Eleanor, additional, Hopkins, Susan, additional, Hall, Victoria, additional, Dold, Christina, additional, Duncan, Christopher J.A., additional, Richter, Alex, additional, Carroll, Miles, additional, Screaton, Gavin, additional, de Silva, Thushan I., additional, Turtle, Lance, additional, Klenerman, Paul, additional, Dunachie, Susanna, additional, Abuelgasim, Hibatullah, additional, Adland, Emily, additional, Adlou, Syed, additional, Akther, Hossain Delowar, additional, Alhussni, Ahmed, additional, Ali, Mohammad, additional, Ansari, M. Azim, additional, Arancibia-Cárcamo, Carolina V., additional, Bayley, Martin, additional, Brown, Helen, additional, Chalk, Jeremy, additional, Chand, Meera, additional, Chawla, Anu, additional, Chinnakannan, Senthil, additional, Cutteridge, Joseph, additional, de Lara, Catherine, additional, Denly, Lucy, additional, Diffey, Ben, additional, Dimitriadis, Stavros, additional, Drake, Thomas M., additional, Donnison, Timothy, additional, Dupont, Maeva, additional, Eyre, David, additional, Fairman, Alex, additional, Gardiner, Siobhan, additional, Gilbert-Jarmillo, Javier, additional, Goulder, Philip, additional, Hackstein, Carl-Philipp, additional, Hambleton, Sophie, additional, Haniffa, Muzlifah, additional, Haworth, Jenny, additional, Holmes, Jennifer, additional, Horner, Emily, additional, Jämsén, Anni, additional, Jones, Chris, additional, Kasanyinga, Mwila, additional, Kelly, Sinead, additional, Kirk, Rosemary, additional, Knight, Michael L., additional, Lawrie, Allan, additional, Lee, Lian, additional, Lett, Lauren, additional, Lillie, Katy, additional, Lim, Nicholas, additional, Mehta, Hema, additional, Mentzer, Alexander J., additional, O’Donnell, Denise, additional, Ogbe, Ane, additional, Pace, Matthew, additional, Payne, Brendan A.I., additional, Platt, Gareth, additional, Poolan, Sonia, additional, Provine, Nicholas, additional, Ramamurthy, Narayan, additional, Robinson, Nichola, additional, Romaniuk, Leigh, additional, Rongkard, Patpong, additional, Sampson, Oliver L., additional, Simmons, Beatrice, additional, Spegarova, Jarmila S., additional, Stephenson, Emily, additional, Subramaniam, Kris, additional, Thaventhiran, James, additional, Thomas, Sarah, additional, Travis, Simon, additional, Tucker, Stephanie, additional, Turton, Helena, additional, Watson, Adam, additional, Watson, Lisa, additional, Weeks, Esme, additional, Wilson, Robert, additional, Wood, Steven, additional, Wright, Rachel, additional, Xiao, Huiyuan, additional, and Zawia, Amira A.T., additional

Published
2021
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34. T cell and antibody responses induced by a single dose of ChAdOx1 nCoV-19 (AZD1222) vaccine in a phase 1/2 clinical trial

Author

Ewer, Katie J., Barrett, Jordan R., Belij-Rammerstorfer, Sandra, Sharpe, Hannah, Makinson, Rebecca, Morter, Richard, Flaxman, Amy, Wright, Daniel, Bellamy, Duncan, Bittaye, Mustapha, Dold, Christina, Provine, Nicholas M., Aboagye, Jeremy, Fowler, Jamie, Silk, Sarah E., Alderson, Jennifer, Aley, Parvinder K., Angus, Brian, Berrie, Eleanor, Bibi, Sagida, Cicconi, Paola, Clutterbuck, Elizabeth A., Chelysheva, Irina, Folegatti, Pedro M., Fuskova, Michelle, Green, Catherine M., Jenkin, Daniel, Kerridge, Simon, Lawrie, Alison, Minassian, Angela M., Moore, Maria, Mujadidi, Yama, Plested, Emma, Poulton, Ian, Ramasamy, Maheshi N., Robinson, Hannah, Song, Rinn, Snape, Matthew D., Tarrant, Richard, Voysey, Merryn, Watson, Marion E. E., Douglas, Alexander D., Hill, Adrian V. S., Gilbert, Sarah C., Pollard, Andrew J., Lambe, Teresa, Ali, Aabidah, Allen, Elizabeth, Baker, Megan, Barnes, Eleanor, Borthwick, Nicola, Boyd, Amy, Brown-O’Sullivan, Charlie, Burgoyne, Joshua, Byard, Nicholas, Puig, Ingrid Cabrera, Cappuccini, Federica, Cho, Jee-Sun, Clark, Elizabeth, Crocker, Wendy E. M., Datoo, Mehreen S., Davies, Hannah, Donnellan, Francesca R., Dunachie, Susanna Jane, Edwards, Nick J., Elias, Sean C., Furze, Julie, Gilbride, Ciaran, Gorini, Giacomo, Gupta, Gaurav, Harris, Stephanie A., Hodgson, Susanne H. C., Hou, Mimi M., Jackson, Susan, Jones, Kathryn, Kailath, Reshma, King, Lloyd, Larkworthy, Colin W., Li, Yuanyuan, Lias, Amelia M., Linder, Aline, Lipworth, Samuel, Ramon, Raquel Lopez, Madhavan, Meera, Marlow, Emma, Marshall, Julia L., Mentzer, Alexander J., Morrison, Hazel, Moya, Nathifa, Mukhopadhyay, Ekta, Noé, Andrés, Nugent, Fay L., Pipini, Dimitra, Pulido-Gomez, David, Lopez, Fernando Ramos, Ritchie, Adam John, Rudiansyah, Indra, Salvador, Stephannie, Sanders, Helen, Satti, Iman, Shea, Adam, Silk, Sarah, Spencer, Alexandra J., Tanner, Rachel, Taylor, Iona Jennifer, Themistocleous, Yrene, Thomas, Merin, Tran, Nguyen, Truby, Adam, Turner, Cheryl, Turner, Nicola, Ulaszewska, Marta, Worth, Andrew T., Kingham-Page, Lucy, Alvarez, Marco Polo Peralta, Anslow, Rachel, Bates, Louise, Beadon, Kirsten, Beckley, Rebecca, Beveridge, Amy, Bijker, Else Margreet, Blackwell, Luke, Burbage, Jamie, Camara, Susana, Carr, Melanie, Colin-Jones, Rachel, Cooper, Rachel, Cunningham, Christina J., Demissie, Tesfaye, Maso, Claudio Di, Douglas, Naomi, Drake-Brockman, Rachael, Drury, Ruth Elizabeth, Emary, Katherine R. W., Felle, Sally, Feng, Shuo, Silva, Carla Ferreira Da, Ford, Karen J., Francis, Emma, Gracie, Lara, Hamlyn, Joseph, Hanumunthadu, Brama, Harrison, Daisy, Hart, Thomas C., Hawkins, Sophia, Hill, Jennifer, Howe, Elizabeth, Howell, Nicola, Jones, Elizabeth, Keen, Jade, Kelly, Sarah, Kerr, David, Khan, Liaquat, Kinch, Jasmin, Koleva, Stanislava, Lees, Emily A., Lelliott, Alice, Liu, Xinxue, Marchevsky, Natalie G., Marinou, Spyridoula, McEwan, Joanne, Morey, Ella, Morshead, Gertraud, Muller, Jilly, Munro, Claire, Murphy, Sarah, Mweu, Philomena, Nuthall, Elizabeth, O’Brien, Katie, O’Connor, Daniel, O’Reilly, Peter John, Oguti, Blanché, Osborne, Piper, Owino, Nelly, Parker, Kaye, Pfafferott, Katja, Phillips, Daniel, Provstgaard-Morys, Samuel, Ratcliffe, Helen, Rawlinson, Thomas, Rhead, Sarah, Roberts, Hannah, Sanders, Katherine, Silva-Reyes, Laura, Rollier, Christine S., Smith, Catherine C., Smith, David J., Stockdale, Lisa, Szigeti, Anna, Thomas, Tonia M., Thompson, Amber, Tomic, Adriana, Tonks, Susan, Varughese, Rachel, Verheul, Marije K., Vichos, Iason, Walker, Laura, White, Caroline, White, Rachel, Yao, Xin Li, Conlon, Christopher P., Frater, John, Cifuentes, Liliana, Baleanu, Ioana, Bolam, Emma, Boland, Elena, Brenner, Tanja, Damratoski, Brad E., Datta, Chandra, Muhanna, Omar El, Fisher, Richard, Galian-Rubio, Pablo, Hodges, Gina, Jackson, Frederic, Liu, Shuchang, Loew, Lisa, Morgans, Roisin, Morris, Susan Jane, Olchawski, Vicki, Oliveria, Catarina, Parracho, Helena, Pabon, Emilia Reyes, Tahiri-Alaoui, Abdessamad, Taylor, Keja, Williams, Paul, Zizi, Dalila, Arbe-Barnes, Edward H., Baker, Philip, Batten, Alexander, Downing, Charlotte, Drake, Jonathan, English, Marcus Rex, Henry, John Aaron, Iveson, Poppy, Killen, Annabel, King, Thomas B., Larwood, Jessica P. J., Mallett, Garry, Mansatta, Kushal, Mirtorabi, Neginsadat, Patrick-Smith, Maia, Perring, James, Radia, Kajal, Roche, Sophie, Schofield, Ella, Naude, Rebecca te Water, Towner, James, Baker, Natalie, Bewley, Kevin R., Brunt, Emily, Buttigieg, Karen R., Carroll, Miles W., Charlton, Sue, Coombes, Naomi S., Elmore, Michael J., Godwin, Kerry, Hallis, Bassam, Knott, Daniel, McInroy, Lorna, Shaik, Imam, Thomas, Kelly, Tree, Julia A., Blundell, Caitlin L., Cao, Michelangelo, Kelly, Dearbhla, Schmid, Annina, Skelly, Donal T., Themistocleous, Andreas, Dong, Tao, Field, Samantha, Hamilton, Elizabeth, Kelly, Elizabeth, Klenerman, Paul, Knight, Julian C., Lie, Yolanda, Petropoulos, Christos, Sedik, Cynthia, Wrin, Terri, Meddaugh, Gretchen, Peng, Yanchun, Screaton, Gavin, and Stafford, Elizabeth

Subjects
0301 basic medicine, biology, business.industry, T cell, Immunogenicity, General Medicine, Vaccine efficacy, General Biochemistry, Genetics and Molecular Biology, Vaccination, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, medicine.anatomical_structure, Immune system, Immunity, 030220 oncology & carcinogenesis, Immunology, biology.protein, medicine, Cytotoxic T cell, Antibody, business
Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus Disease 2019 (COVID-19), has caused a global pandemic, and safe, effective vaccines are urgently needed1. Strong, Th1-skewed T cell responses can drive protective humoral and cell-mediated immune responses2 and might reduce the potential for disease enhancement3. Cytotoxic T cells clear virus-infected host cells and contribute to control of infection4. Studies of patients infected with SARS-CoV-2 have suggested a protective role for both humoral and cell-mediated immune responses in recovery from COVID-19 (refs. 5,6). ChAdOx1 nCoV-19 (AZD1222) is a candidate SARS-CoV-2 vaccine comprising a replication-deficient simian adenovirus expressing full-length SARS-CoV-2 spike protein. We recently reported preliminary safety and immunogenicity data from a phase 1/2 trial of the ChAdOx1 nCoV-19 vaccine (NCT04400838)7 given as either a one- or two-dose regimen. The vaccine was tolerated, with induction of neutralizing antibodies and antigen-specific T cells against the SARS-CoV-2 spike protein. Here we describe, in detail, exploratory analyses of the immune responses in adults, aged 18–55 years, up to 8 weeks after vaccination with a single dose of ChAdOx1 nCoV-19 in this trial, demonstrating an induction of a Th1-biased response characterized by interferon-γ and tumor necrosis factor-α cytokine secretion by CD4+ T cells and antibody production predominantly of IgG1 and IgG3 subclasses. CD8+ T cells, of monofunctional, polyfunctional and cytotoxic phenotypes, were also induced. Taken together, these results suggest a favorable immune profile induced by ChAdOx1 nCoV-19 vaccine, supporting the progression of this vaccine candidate to ongoing phase 2/3 trials to assess vaccine efficacy. A single dose of the ChAdOx1 nCoV-19 vaccine elicits antibodies and cytokine-producing T cells that might help control or prevent SARS-CoV-2 infection.

Published
2020
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35. T cell assays differentiate clinical and subclinical SARS-CoV-2 infections from cross-reactive antiviral responses

Author

Ogbe, Ane, Kronsteiner, Barbara, Skelly, Donal T, Pace, Matthew, Brown, Anthony, Adland, Emily, Adair, Kareena, Akhter, Hossain Delowar, Ali, Mohammad, Ali, Serat-E, Angyal, Adrienn, Ansari, M Azim, Arancibia-Carcamo, Carolina V, Brown, Helen, Chinnakannan, Senthil, Conlon, Christopher, de Lara, Catherine, de Silva, Thushan, Dold, Christina, Dong, Tao, Donnison, Timothy, Eyre, David, Flaxman, Amy, Fletcher, Helen, Gardner, Joshua, Grist, James T, Hackstein, Carl-Philipp, Jaruthamsophon, Kanoot, Jeffery, Katie, Lambe, Teresa, Lee, Lian, Li, Wenqin, Lim, Nicholas, Matthews, Philippa C, Mentzer, Alexander J, Moore, Shona C, Naisbitt, Dean J, Ogese, Monday, Ogg, Graham, Openshaw, Peter, Pirmohamed, Munir, Pollard, Andrew J, Ramamurthy, Narayan, Rongkard, Patpong, Rowland-Jones, Sarah, Sampson, Oliver, Screaton, Gavin, Sette, Alessandro, Stafford, Lizzie, Thompson, Craig, Thomson, Paul J, Thwaites, Ryan, Vieira, Vinicius, Weiskopf, Daniela, Zacharopoulou, Panagiota, Chalk, Jeremy, Kerr, Georgina, Phalora, Prabhjeet, Csala, Anna, Jones, Mathew, Robinson, Nicola, Brown, Rachael, Hutchings, Claire, Provine, Nicholas, Ratcliff, Jeremy, Amini, Ali, Borak, Martyna, Dimitriadis, Stavros, Fordwoh, Thomas, Horsington, Bryn, Johnson, Sile, Morrow, Jordan, Warren, Yolanda, Wells, Charlie, Turtle, Lance, Klenerman, Paul, Goulder, Philip, Frater, John, Barnes, Eleanor, Dunachie, Susanna, Immunology, Oxford, and Oxford, Protective TC

Subjects
0301 basic medicine, CD4-Positive T-Lymphocytes, animal diseases, T-Lymphocytes, General Physics and Astronomy, CD8-Positive T-Lymphocytes, Immunological memory, 0302 clinical medicine, 030212 general & internal medicine, Subclinical infection, Immunoassay, Multidisciplinary, ELISPOT, 3. Good health, Multidisciplinary Sciences, medicine.anatomical_structure, Science & Technology - Other Topics, VIRUS, Cytokines, Science, T cell, Health Personnel, Oxford Protective T Cell Immunology for COVID-19 (OPTIC) Clinical Team, chemical and pharmacologic phenomena, Biology, Cross Reactions, Antiviral Agents, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, Interferon-gamma, Immune system, Antigen, Immunity, medicine, Humans, Pandemics, Cell Proliferation, Science & Technology, Cell growth, SARS-CoV-2, Oxford Immunology Network Covid-19 Response T Cell Consortium, COVID-19, General Chemistry, biochemical phenomena, metabolism, and nutrition, 030104 developmental biology, HEK293 Cells, Viral infection, Immunoglobulin G, Immunology, bacteria, Peptides, Immunologic Memory, Ex vivo
Abstract

Identification of protective T cell responses against SARS-CoV-2 requires distinguishing people infected with SARS-CoV-2 from those with cross-reactive immunity to other coronaviruses. Here we show a range of T cell assays that differentially capture immune function to characterise SARS-CoV-2 responses. Strong ex vivo ELISpot and proliferation responses to multiple antigens (including M, NP and ORF3) are found in 168 PCR-confirmed SARS-CoV-2 infected volunteers, but are rare in 119 uninfected volunteers. Highly exposed seronegative healthcare workers with recent COVID-19-compatible illness show T cell response patterns characteristic of infection. By contrast, >90% of convalescent or unexposed people show proliferation and cellular lactate responses to spike subunits S1/S2, indicating pre-existing cross-reactive T cell populations. The detection of T cell responses to SARS-CoV-2 is therefore critically dependent on assay and antigen selection. Memory responses to specific non-spike proteins provide a method to distinguish recent infection from pre-existing immunity in exposed populations., Understanding the immune response to SARS-CoV-2 is dependent on being able to distinguish COVID-19 immune responses from cross-reactive immune responses to other coronaviruses. Here the authors show that choice of antigens and whether an ICS, ELISPOT or T cell proliferation assay is used has a major effect on this discriminatory ability.

Published
2020

36. MAIT cell activation augments adenovirus vector vaccine immunogenicity

Author

Provine, Nicholas M., primary, Amini, Ali, additional, Garner, Lucy C., additional, Spencer, Alexandra J., additional, Dold, Christina, additional, Hutchings, Claire, additional, Silva Reyes, Laura, additional, FitzPatrick, Michael E. B., additional, Chinnakannan, Senthil, additional, Oguti, Blanche, additional, Raymond, Meriel, additional, Ulaszewska, Marta, additional, Troise, Fulvia, additional, Sharpe, Hannah, additional, Morgan, Sophie B., additional, Hinks, Timothy S. C., additional, Lambe, Teresa, additional, Capone, Stefania, additional, Folgori, Antonella, additional, Barnes, Eleanor, additional, Rollier, Christine S., additional, Pollard, Andrew J., additional, and Klenerman, Paul, additional

Published
2021
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37. Human intestinal tissue-resident memory T cells comprise transcriptionally and functionally distinct subsets

Author

FitzPatrick, Michael E.B., primary, Provine, Nicholas M., additional, Garner, Lucy C., additional, Powell, Kate, additional, Amini, Ali, additional, Irwin, Sophie L., additional, Ferry, Helen, additional, Ambrose, Tim, additional, Friend, Peter, additional, Vrakas, Georgios, additional, Reddy, Srikanth, additional, Soilleux, Elizabeth, additional, Klenerman, Paul, additional, and Allan, Philip J., additional

Published
2021
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39. Fatal COVID-19 Outcomes are Associated with an Antibody Response Targeting Epitopes Shared with Endemic Coronaviruses

Author

McNaughton, Anna L., primary, Paton, Robert S., additional, Edmans, Matthew, additional, Youngs, Jonathan, additional, Wellens, Judith, additional, Phalora, Prabhjeet, additional, Fyfe, Alex, additional, Belij-rammerstorfer, Sandra, additional, Bolton, Jai S., additional, Ball, Jonathan, additional, Carnell, George, additional, Dejnirattisai, Wanwisa, additional, Dold, Christina, additional, Eyre, David W., additional, Hopkins, Philip, additional, Howarth, Alison, additional, Kooblall, Kreepa, additional, Klim, Hannah, additional, Leaver, Susannah, additional, Lee, Lian, additional, Lopez-Camacho, Cesar, additional, Lumley, Sheila, additional, Macallan, Derek, additional, Mentzer, Alexander J., additional, Provine, Nicholas, additional, Ratcliff, Jeremy, additional, Slon-Campos, Jose, additional, Skelly, Donal, additional, Stolle, Lucas, additional, Supasa, Piyada, additional, Temperton, Nigel, additional, Walker, Chris, additional, Wang, Beibei, additional, Wyncoll, Duncan, additional, consortium, OPTIC, additional, consortium, SNBTS, additional, Simmonds, Peter, additional, Lambe, Teresa, additional, Baillie, J. Kenneth, additional, Semple, Malcolm, additional, Openshaw, Peter, additional, Obolski, Uri, additional, Turner, Marc, additional, Carroll, Miles W., additional, Mongkolspaya, Juthathip, additional, Screaton, Gavin R., additional, Kennedy, Stephen H., additional, Jarvis, Lisa, additional, Barnes, Eleanor, additional, Dunachie, Susanna, additional, Lourenço, José, additional, Matthews, Philippa, additional, Bicanic, Tihana, additional, Klenerman, Paul, additional, Gupta, Sunetra, additional, and Thompson, Craig P., additional

Published
2021
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40. Successful treatment of COVID-19 with remdesivir in the absence of humoral immunity

Author

Buckland, Matthew S, primary, Galloway, James, additional, Fhogartaig, Caoimhe Nic, additional, Meredith, Luke, additional, Provine, Nicholas M., additional, Bloor, Stuart, additional, Ogbe, Ane, additional, Zelek, Wioleta M., additional, Smielewska, Anna, additional, Yakovleva, Anna, additional, Mann, Tiffeney, additional, Bergamaschi, Laura, additional, Turner, Lorinda, additional, Mescia, Frederica, additional, Toonen, Erik J.M., additional, Hackstein, Carl-Philipp, additional, Akther, Hossain Delowar, additional, Vieira, Vinicius Adriano, additional, Ceron-Gutierrez, Lourdes, additional, Periselneris, Jimstan, additional, Kiani-Alikhan, Sorena, additional, Grigoriadou, Sofia, additional, Vaghela, Devan, additional, Lear, Sara E., additional, Torok, Estee, additional, Hamilton, William L., additional, Quick, Josh, additional, Stockton, Joanne, additional, Nelson, Peter, additional, Hunter, Michael, additional, Coulter, Tanya I, additional, Devlin, Lisa, additional, Bradley, John, additional, Smith, Ken, additional, Ouwehand, Willem, additional, Estcourt, Lise, additional, Simmonds, Heli Harvala, additional, Roberts, Dave, additional, Wilkinson, Ian, additional, Screaton, Nick, additional, Loman, Nick, additional, Lyons, Paul, additional, Doffinger, Rainer, additional, Morgan, Paul, additional, Goodfellow, Ian, additional, Klenerman, Paul, additional, Lehner, Paul, additional, Matheson, Nick, additional, and Thaventhiran, James, additional

Published
2020
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43. Human intestinal tissue-resident memory CD8+ T cells comprise transcriptionally and functionally distinct subsets

Author

FitzPatrick, Michael E.B., primary, Provine, Nicholas M., additional, Garner, Lucy C., additional, Powell, Kate, additional, Amini, Ali, additional, Irwin, Sophie, additional, Ferry, Helen, additional, Ambrose, Tim, additional, Friend, Peter, additional, Vrakas, Georgios, additional, Reddy, Srikanth, additional, Soilleux, Elizabeth, additional, Klenerman, Paul, additional, and Allan, Philip J., additional

Published
2019
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44. Identification of immune correlates of fatal outcomes in critically ill COVID-19 patients.

Author

Youngs, Jonathan, Provine, Nicholas M., Lim, Nicholas, Sharpe, Hannah R., Amini, Ali, Chen, Yi-Ling, Luo, Jian, Edmans, Matthew D., Zacharopoulou, Panagiota, Chen, Wentao, Sampson, Oliver, Paton, Robert, Hurt, William J., Duncan, David A., McNaughton, Anna L., Miao, Vincent N., Leaver, Susannah, Wyncoll, Duncan L. A., Ball, Jonathan, and Hopkins, Philip

Subjects
*COVID-19, *MEDICAL personnel, *INFLUENZA, *CRITICALLY ill, *BLOOD proteins, *T cells, *ADULTS, *CEREBROSPINAL fluid
Abstract

Prior studies have demonstrated that immunologic dysfunction underpins severe illness in COVID-19 patients, but have lacked an in-depth analysis of the immunologic drivers of death in the most critically ill patients. We performed immunophenotyping of viral antigen-specific and unconventional T cell responses, neutralizing antibodies, and serum proteins in critically ill patients with SARS-CoV-2 infection, using influenza infection, SARS-CoV-2-convalescent health care workers, and healthy adults as controls. We identify mucosal-associated invariant T (MAIT) cell activation as an independent and significant predictor of death in COVID-19 (HR = 5.92, 95% CI = 2.49–14.1). MAIT cell activation correlates with several other mortality-associated immunologic measures including broad activation of CD8+ T cells and non-Vδ2 γδT cells, and elevated levels of cytokines and chemokines, including GM-CSF, CXCL10, CCL2, and IL-6. MAIT cell activation is also a predictor of disease severity in influenza (ECMO/death HR = 4.43, 95% CI = 1.08–18.2). Single-cell RNA-sequencing reveals a shift from focused IFNα-driven signals in COVID-19 ICU patients who survive to broad pro-inflammatory responses in fatal COVID-19 –a feature not observed in severe influenza. We conclude that fatal COVID-19 infection is driven by uncoordinated inflammatory responses that drive a hierarchy of T cell activation, elements of which can serve as prognostic indicators and potential targets for immune intervention. Author summary: We examined the immune abnormalities linked to critical illness and death in COVID-19 patients on ICU, performing immunophenotyping of viral antigen-specific and unconventional T cell responses, together with studies of neutralizing antibodies, and serum proteins. We compared these findings to a parallel set of patients with severe influenza. From this screen we identified mucosal-associated invariant T (MAIT) cell activation as an independent and significant predictor of death in COVID-19. MAIT cell activation correlated with several other mortality-associated immunologic measures including elevated levels of cytokines and chemokines, such as GM-CSF and CXCL10. MAIT cell activation is also a predictor of disease severity in influenza. Single-cell RNA-sequencing revealed a shift from focused IFNα-driven signals in COVID-19 ICU patients who survive to broad pro-inflammatory responses in fatal COVID-19 –a feature not observed in severe influenza. Overall we observed key potential biomarkers and targetable pathways in critical viral illness, many shared between influenza and COVID-19 and some unique to each infection. [ABSTRACT FROM AUTHOR]

Published
2021
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45. Unique and Common Features of Innate-Like Human Vδ2+ γδT Cells and Mucosal-Associated Invariant T Cells

Author

Provine, Nicholas M., Binder, Benedikt, FitzPatrick, Michael E. B., Schuch, Anita, Garner, Lucy C., Williamson, Kate D., van Wilgenburg, Bonnie, Thimme, Robert, Klenerman, Paul, and Hofmann, Maike

Subjects
hepatitis C virus, Adult, Male, Immunology, Receptors, Antigen, T-Cell, gamma-delta, mucosal-associated invariant T, Hepatitis C, Chronic, Middle Aged, Vδ2 γδ T cells, Lymphocyte Activation, γδ T cells, Mucosal-Associated Invariant T Cells, mucosal immunology, T-Lymphocyte Subsets, Humans, Female, Original Research, innate-like T cells
Abstract

Mucosal-associated invariant T (MAIT) cells are innate-like T cells abundant in humans that can be activated in a TCR-independent manner by inflammatory and antiviral cytokines. In humans, the capacity for TCR-independent activation is functionally linked to a transcriptional program that can be identified by the expression of the C-type lectin receptor, CD161. In addition to MAIT cells, it has been demonstrated that a subset of γδT cells expresses CD161 and can be activated by TCR-independent cytokine stimulation. In this study, we sought to clarify the nature of cytokine-responsive human γδT cells. We could link CD161 expression on Vδ2+ versus Vδ1+ γδT cells to the observation that Vδ2+ γδT cells, but not Vδ1+ γδT cells, robustly produced IFN-γ upon stimulation with a variety of cytokine combinations. Interestingly, both CD161+ and CD161− Vδ2+ γδT cells responded to these stimuli, with increased functionality within the CD161+ subset. This innate-like responsiveness corresponded to high expression of PLZF and IL-18Rα, analogous to MAIT cells. Vδ2+ γδT cells in human duodenum and liver maintained a CD161+ IL-18Rα+ phenotype and produced IFN-γ in response to IL-12 and IL-18 stimulation. In contrast to MAIT cells, we could not detect IL-17A production but observed higher steady-state expression of Granzyme B by Vδ2+ γδT cells. Finally, we investigated the frequency and functionality of γδT cells in the context of chronic hepatitis C virus infection, as MAIT cells are reduced in frequency in this disease. By contrast, Vδ2+ γδT cells were maintained in frequency and displayed unimpaired IFN-γ production in response to cytokine stimulation. In sum, human Vδ2+ γδT cells are a functionally distinct population of cytokine-responsive innate-like T cells that is abundant in blood and tissues with similarities to human MAIT cells.

Published
2018

48. Activation of MAIT cells plays a critical role in viral vector vaccine immunogenicity

Author

Provine, Nicholas M., primary, Amini, Ali, additional, Garner, Lucy C., additional, Dold, Christina, additional, Hutchings, Claire, additional, FitzPatrick, Michael E.B., additional, Reyes, Laura Silva, additional, Chinnakannan, Senthil, additional, Oguti, Blanche, additional, Raymond, Meriel, additional, Capone, Stefania, additional, Folgori, Antonella, additional, Rollier, Christine S., additional, Barnes, Eleanor, additional, Pollard, Andrew J., additional, and Klenerman, Paul, additional

Published
2019
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49. Adenovirus vectors activate Vδ2+ γδT cells in a type I interferon‐, TNF‐, and IL‐18‐dependent manner.

Author

Provine, Nicholas M., Amini, Ali, Garner, Lucy C., FitzPatrick, Michael E.B., Dold, Christina, Silva Reyes, Laura, Chinnakannan, Senthil, Oguti, Blanche, Raymond, Meriel, Troise, Fulvia, Capone, Stefania, Folgori, Antonella, Barnes, Eleanor, Rollier, Christine S., Pollard, Andrew J., and Klenerman, Paul

Subjects
GENETIC transformation, GENETIC vectors, MONONUCLEAR leukocytes, ADENOVIRUSES, CYTOTOXIC T cells, KILLER cells, TYPE I interferons
Abstract

Adenovirus vectors activate V 2+ T cells in a type I interferon-, TNF-, and IL-18-dependent manner V 2 SP + sp T cells are unconventional T cells that can be activated by cytokines without TCR signaling. We examined three species C vectors (Ad5, Ad6, and ChAdN13) and five non-species C vectors (Ad24, Ad35, ChAd63, ChAd68, and ChAdOx1), and found that on average, the non-species C vectors induced significantly more V 2 SP + sp T cell IFN- production (Fig. Adenovirus vaccine vectors activated V 2 SP + sp T cells in an interleukin 18-, TNF-, and type I interferon-dependent manner. [Extracted from the article]

Published
2022
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50. Treatment of COVID-19 with remdesivir in the absence of humoral immunity: a case report.

Author

Buckland, Matthew S., Galloway, James B., Fhogartaigh, Caoimhe Nic, Meredith, Luke, Provine, Nicholas M., Bloor, Stuart, Ogbe, Ane, Zelek, Wioleta M., Smielewska, Anna, Yakovleva, Anna, Mann, Tiffeney, Bergamaschi, Laura, Turner, Lorinda, Mescia, Frederica, Toonen, Erik J. M., Hackstein, Carl-Philipp, Akther, Hossain Delowar, Vieira, Vinicius Adriano, Ceron-Gutierrez, Lourdes, and Periselneris, Jimstan

Subjects
COVID-19 treatment, COVID-19, PANDEMICS, REMDESIVIR, HUMORAL immunity, COMPLEMENT receptors, EXPERIMENTAL medicine
Abstract

The response to the coronavirus disease 2019 (COVID-19) pandemic has been hampered by lack of an effective severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antiviral therapy. Here we report the use of remdesivir in a patient with COVID-19 and the prototypic genetic antibody deficiency X-linked agammaglobulinaemia (XLA). Despite evidence of complement activation and a robust T cell response, the patient developed persistent SARS-CoV-2 pneumonitis, without progressing to multi-organ involvement. This unusual clinical course is consistent with a contribution of antibodies to both viral clearance and progression to severe disease. In the absence of these confounders, we take an experimental medicine approach to examine the in vivo utility of remdesivir. Over two independent courses of treatment, we observe a temporally correlated clinical and virological response, leading to clinical resolution and viral clearance, with no evidence of acquired drug resistance. We therefore provide evidence for the antiviral efficacy of remdesivir in vivo, and its potential benefit in selected patients. Remdesivir is under evaluation for treatment of COVID-19 in clinical trials. Here, the authors report results of remdesivir treatment in a patient with COVID-19 and the genetic antibody deficiency XLA. They show a temporally correlated clinical and virological response, suggesting that remdesivir can reduce SARS-CoV-2 replication in patients. [ABSTRACT FROM AUTHOR]

Published
2020
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