Author: "Adriana Tomic" - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Adriana Tomic"' showing total 24 results

Start Over Author "Adriana Tomic"

24 results on '"Adriana Tomic"'

1. Omicron infection following vaccination enhances a broad spectrum of immune responses dependent on infection history

Author: Hailey Hornsby, Alexander R. Nicols, Stephanie Longet, Chang Liu, Adriana Tomic, Adrienn Angyal, Barbara Kronsteiner, Jessica K. Tyerman, Tom Tipton, Peijun Zhang, Marta Gallis, Piyada Supasa, Muneeswaran Selvaraj, Priyanka Abraham, Isabel Neale, Mohammad Ali, Natalie A. Barratt, Jeremy M. Nell, Lotta Gustafsson, Scarlett Strickland, Irina Grouneva, Timothy Rostron, Shona C. Moore, Luisa M. Hering, Susan L. Dobson, Sagida Bibi, Juthathip Mongkolsapaya, Teresa Lambe, Dan Wootton, Victoria Hall, Susan Hopkins, Tao Dong, Eleanor Barnes, Gavin Screaton, The PITCH Consortium, Alex Richter, Lance Turtle, Sarah L. Rowland-Jones, Miles Carroll, Christopher J. A. Duncan, Paul Klenerman, Susanna J. Dunachie, Rebecca P. Payne, and Thushan I. de Silva
Subjects: Science
Abstract: Abstract Pronounced immune escape by the SARS-CoV-2 Omicron variant has resulted in many individuals possessing hybrid immunity, generated through a combination of vaccination and infection. Concerns have been raised that omicron breakthrough infections in triple-vaccinated individuals result in poor induction of omicron-specific immunity, and that prior SARS-CoV-2 infection is associated with immune dampening. Taking a broad and comprehensive approach, we characterize mucosal and blood immunity to spike and non-spike antigens following BA.1/BA.2 infections in triple mRNA-vaccinated individuals, with and without prior SARS-CoV-2 infection. We find that most individuals increase BA.1/BA.2/BA.5-specific neutralizing antibodies following infection, but confirm that the magnitude of increase and post-omicron titres are higher in the infection-naive. In contrast, significant increases in nasal responses, including neutralizing activity against BA.5 spike, are seen regardless of infection history. Spike-specific T cells increase only in infection-naive vaccinees; however, post-omicron T cell responses are significantly higher in the previously-infected, who display a maximally induced response with a highly cytotoxic CD8+ phenotype following their 3rd mRNA vaccine dose. Responses to non-spike antigens increase significantly regardless of prior infection status. These findings suggest that hybrid immunity induced by omicron breakthrough infections is characterized by significant immune enhancement that can help protect against future omicron variants.
Published: 2023
Full Text: View/download PDF

2. CD4+ and CD8+ T cells and antibodies are associated with protection against Delta vaccine breakthrough infection: a nested case-control study within the PITCH study

Author: Isabel Neale, Mohammad Ali, Barbara Kronsteiner, Stephanie Longet, Priyanka Abraham, Alexandra S. Deeks, Anthony Brown, Shona C. Moore, Lizzie Stafford, Susan L. Dobson, Megan Plowright, Thomas A. H. Newman, Mary Y. Wu, Edward J. Carr, Rupert Beale, Ashley D. Otter, Susan Hopkins, Victoria Hall, Adriana Tomic, Rebecca P. Payne, Eleanor Barnes, Alex Richter, Christopher J. A. Duncan, Lance Turtle, Thushan I. de Silva, Miles Carroll, Teresa Lambe, Paul Klenerman, and Susanna Dunachie
Subjects: SARS-CoV-2, COVID-19, COVID vaccine, T cells, antibody, immunity, Microbiology, QR1-502
Abstract: ABSTRACT Serological correlates of protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection after vaccination (“vaccine breakthrough”) have been described. However, T cell correlates of protection against breakthrough are incompletely defined, especially the specific contributions of CD4+ and CD8+ T cells. Here, 279 volunteers in the Protective Immunity from T Cells in Healthcare Workers (PITCH) UK cohort study were enrolled in a nested case-control study. Cases were those who tested SARS-CoV-2 PCR or lateral flow device (LFD) positive after two vaccine doses during the Delta-predominant era (n = 32), while controls were those who did not report a positive test or undergo anti-nucleocapsid immunoglobulin G (IgG) seroconversion during this period (n = 247). Previous SARS-CoV-2 infection prior to vaccination was associated with reduced odds of vaccine breakthrough. Using samples from 28 d after the second vaccine dose, before all breakthroughs occurred, we observed future cases had lower ancestral spike (S)- and receptor binding domain-specific IgG titers and S1- and S2-specific T cell interferon gamma (IFNγ) responses compared with controls, although these differences did not persist when individuals were stratified according to previous infection status before vaccination. In a subset of matched infection-naïve cases and controls, vaccine breakthrough cases had lower CD4+ and CD8+ IFNγ and tumor necrosis factor (TNF) responses to Delta S peptides compared with controls. For CD8+ responses, this difference appeared to be driven by reduced responses to Delta compared with ancestral peptides among cases; this reduced response to Delta peptides was not observed in controls. Our findings support a protective role for T cells against Delta breakthrough infection. IMPORTANCE Defining correlates of protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine breakthrough infection informs vaccine policy for booster doses and future vaccine designs. Existing studies demonstrate humoral correlates of protection, but the role of T cells in protection is still unclear. In this study, we explore antibody and T cell immune responses associated with protection against Delta variant vaccine breakthrough infection in a well-characterized cohort of UK Healthcare Workers (HCWs). We demonstrate evidence to support a role for CD4+ and CD8+ T cells as well as antibodies against Delta vaccine breakthrough infection. In addition, our results suggest a potential role for cross-reactive T cells in vaccine breakthrough.
Published: 2023
Full Text: View/download PDF

3. Divergent trajectories of antiviral memory after SARS-CoV-2 infection

Author: Adriana Tomic, Donal T. Skelly, Ane Ogbe, Daniel O’Connor, Matthew Pace, Emily Adland, Frances Alexander, Mohammad Ali, Kirk Allott, M. Azim Ansari, Sandra Belij-Rammerstorfer, Sagida Bibi, Luke Blackwell, Anthony Brown, Helen Brown, Breeze Cavell, Elizabeth A. Clutterbuck, Thushan de Silva, David Eyre, Sheila Lumley, Amy Flaxman, James Grist, Carl-Philipp Hackstein, Rachel Halkerston, Adam C. Harding, Jennifer Hill, Tim James, Cecilia Jay, Síle A. Johnson, Barbara Kronsteiner, Yolanda Lie, Aline Linder, Stephanie Longet, Spyridoula Marinou, Philippa C. Matthews, Jack Mellors, Christos Petropoulos, Patpong Rongkard, Cynthia Sedik, Laura Silva-Reyes, Holly Smith, Lisa Stockdale, Stephen Taylor, Stephen Thomas, Timothy Tipoe, Lance Turtle, Vinicius Adriano Vieira, Terri Wrin, OPTIC Clinical Group, PITCH Study Group, C-MORE Group, Andrew J. Pollard, Teresa Lambe, Chris P. Conlon, Katie Jeffery, Simon Travis, Philip Goulder, John Frater, Alex J. Mentzer, Lizzie Stafford, Miles W. Carroll, William S. James, Paul Klenerman, Eleanor Barnes, Christina Dold, and Susanna J. Dunachie
Subjects: Science
Abstract: The engagement of immunological memory is a key component to the protective anti-SARS-CoV-2 B and T cell responses. Here the authors assess the B and T cells of a cohort of UK healthcare workers in response to infection and longitudinally track the compartment showing distinct trajectories following early priming.
Published: 2022
Full Text: View/download PDF

4. SIMON: Open-Source Knowledge Discovery Platform

Author: Adriana Tomic, Ivan Tomic, Levi Waldron, Ludwig Geistlinger, Max Kuhn, Rachel L. Spreng, Lindsay C. Dahora, Kelly E. Seaton, Georgia Tomaras, Jennifer Hill, Niharika A. Duggal, Ross D. Pollock, Norman R. Lazarus, Stephen D.R. Harridge, Janet M. Lord, Purvesh Khatri, Andrew J. Pollard, and Mark M. Davis
Subjects: machine learning, data science, data mining, software, systems biology, computational biology, Computer software, QA76.75-76.765
Abstract: Summary: Data analysis and knowledge discovery has become more and more important in biology and medicine with the increasing complexity of biological datasets, but the necessarily sophisticated programming skills and in-depth understanding of algorithms needed pose barriers to most biologists and clinicians to perform such research. We have developed a modular open-source software, SIMON, to facilitate the application of 180+ state-of-the-art machine-learning algorithms to high-dimensional biomedical data. With an easy-to-use graphical user interface, standardized pipelines, and automated approach for machine learning and other statistical analysis methods, SIMON helps to identify optimal algorithms and provides a resource that empowers non-technical and technical researchers to identify crucial patterns in biomedical data. The Bigger Picture: Over the past years, technological advances have enabled the generation of large amounts of data at multiple scales. The integration of high-dimensional data is particularly important in biomedical sciences, as they can be used to identify biological mechanisms and predict clinical outcomes well in advance of their occurrence. Because of the lack of powerful analytical tools that can be used by the average biomedical researcher, translation of such knowledge has been extremely slow. We have developed an open-source software, SIMON, to facilitate the application of machine learning to high-dimensional biomedical data. In SIMON, analysis is performed using an intuitive graphical user interface and standardized, automated machine learning approach allowing non-technical researchers to identify patterns and extract knowledge from high-dimensional data and build high-quality predictive models.
Published: 2021
Full Text: View/download PDF

5. Gene expression profiling reveals insights into infant immunological and febrile responses to group B meningococcal vaccine

Author: 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, and Andrew J Pollard
Subjects: paediatrics, proteomics, systems biology, transcriptomics, vaccines, Biology (General), QH301-705.5, Medicine (General), R5-920
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.
Published: 2020
Full Text: View/download PDF

6. Systems Immunology: Revealing Influenza Immunological Imprint

Author: Adriana Tomic, Andrew J. Pollard, and Mark M. Davis
Subjects: systems immunology, influenza, influenza vaccines, protective immunity, machine learning, data mining, Microbiology, QR1-502
Abstract: Understanding protective influenza immunity and identifying immune correlates of protection poses a major challenge and requires an appreciation of the immune system in all of its complexity. While adaptive immune responses such as neutralizing antibodies and influenza-specific T lymphocytes are contributing to the control of influenza virus, key factors of long-term protection are not well defined. Using systems immunology, an approach that combines experimental and computational methods, we can capture the systems-level state of protective immunity and reveal the essential pathways that are involved. New approaches and technological developments in systems immunology offer an opportunity to examine roles and interrelationships of clinical, biological, and genetic factors in the control of influenza infection and have the potential to lead to novel discoveries about influenza immunity that are essential for the development of more effective vaccines to prevent future pandemics. Here, we review recent developments in systems immunology that help to reveal key factors mediating protective immunity.
Published: 2021
Full Text: View/download PDF

7. Cytomegalovirus m154 hinders CD48 cell-surface expression and promotes viral escape from host natural killer cell control.

Author: Angela Zarama, Natàlia Pérez-Carmona, Domènec Farré, Adriana Tomic, Eva Maria Borst, Martin Messerle, Stipan Jonjic, Pablo Engel, and Ana Angulo
Subjects: Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5
Abstract: Receptors of the signalling lymphocyte-activation molecules (SLAM) family are involved in the functional regulation of a variety of immune cells upon engagement through homotypic or heterotypic interactions amongst them. Here we show that murine cytomegalovirus (MCMV) dampens the surface expression of several SLAM receptors during the course of the infection of macrophages. By screening a panel of MCMV deletion mutants, we identified m154 as an immunoevasin that effectively reduces the cell-surface expression of the SLAM family member CD48, a high-affinity ligand for natural killer (NK) and cytotoxic T cell receptor CD244. m154 is a mucin-like protein, expressed with early kinetics, which can be found at the cell surface of the infected cell. During infection, m154 leads to proteolytic degradation of CD48. This viral protein interferes with the NK cell cytotoxicity triggered by MCMV-infected macrophages. In addition, we demonstrate that an MCMV mutant virus lacking m154 expression results in an attenuated phenotype in vivo, which can be substantially restored after NK cell depletion in mice. This is the first description of a viral gene capable of downregulating CD48. Our novel findings define m154 as an important player in MCMV innate immune regulation.
Published: 2014
Full Text: View/download PDF

8. Omicron BA.1/BA.2 infections in triple-vaccinated individuals enhance a diverse repertoire of mucosal and blood immune responses

Author: Hailey Hornsby, Alexander R. Nicols, Stephanie Longet, Chang Liu, Adriana Tomic, Adrienn Angyal, Barbara Kronsteiner, Jessica K. Tyerman, Tom Tipton, Peijun Zhang, Marta Gallis Ramalho, Piyada Supasa, Muneeswaran Selvaraj, Priyanka Abraham, Isabel Neale, Mohammad Ali, Natalie A. Barratt, Jeremy M. Nell, Lotta Gustafsson, Scarlett Strickland, Irina Grouneva, Timothy Rostron, Shona C. Moore, Luisa M. Hering, Susan L. Dobson, Sagida Bibi, Juthathip Mongkolsapaya, Teresa Lambe, Dan Wootton, Victoria Hall, Susan Hopkins, Tao Dong, Eleanor Barnes, Gavin Screaton, Alex Richter, Lance Turtle, Sarah L. Rowland-Jones, Miles Carroll, Christopher J.A. Duncan, Paul Klenerman, Susanna J. Dunachie, Rebecca P. Payne, and Thushan I. de Silva
Abstract: Pronounced immune escape by the SARS-CoV-2 Omicron variant has resulted in large numbers of individuals with hybrid immunity, generated through a combination of vaccination and infection. Based primarily on circulating neutralizing antibody (NAb) data, concerns have been raised that omicron breakthrough infections in triple-vaccinated individuals result in poor induction of omicron-specific immunity, and that a history of prior SARS-CoV-2 in particular is associated with profound immune dampening. Taking a broader and comprehensive approach, we characterized mucosal and blood immunity to both spike and non-spike antigens following BA.1/BA.2 infections in triple mRNA-vaccinated individuals, with and without a history of previous SARS-CoV-2 infection. We find that the majority of individuals increase BA.1/BA.2/BA.5-specific NAb following infection, but confirm that the magnitude of increase and post-omicron titres are indeed higher in those who were infection-naive. In contrast, significant increases in nasal antibody responses are seen regardless of prior infection history, including neutralizing activity against BA.5 spike. Spike-specific T cells increase only in infection-naive vaccinees; however, post-omicron T cell responses are still significantly higher in previously-infected individuals, who appear to have maximally induced responses with a CD8+ phenotype of high cytotoxic potential after their 3rdmRNA vaccine dose. Antibody and T cell responses to non-spike antigens also increase significantly regardless of prior infection status, with a boost seen in previously-infected individuals to immunity primed by their first infection. These findings suggest that hybrid immunity induced by omicron breakthrough infections is highly dynamic, complex, and compartmentalised, with significant immune enhancement that can help protect against COVID-19 caused by future omicron variants.
Published: 2023

9. Constructing custom-made radiotranscriptomic signatures of vascular inflammation from routine CT angiograms: a prospective outcomes validation study in COVID-19

Author: Christos P Kotanidis, Cheng Xie, Donna Alexander, Jonathan C L Rodrigues, Katie Burnham, Alexander Mentzer, Daniel O’Connor, Julian Knight, Muhammad Siddique, Helen Lockstone, Sheena Thomas, Rafail Kotronias, Evangelos K Oikonomou, Ileana Badi, Maria Lyasheva, Cheerag Shirodaria, Sheila F Lumley, Bede Constantinides, Nicholas Sanderson, Gillian Rodger, Kevin K Chau, Archie Lodge, Maria Tsakok, Fergus Gleeson, David Adlam, Praveen Rao, Das Indrajeet, Aparna Deshpande, Amrita Bajaj, Benjamin J Hudson, Vivek Srivastava, Shakil Farid, George Krasopoulos, Rana Sayeed, Ling-Pei Ho, Stefan Neubauer, David E Newby, Keith M Channon, John Deanfield, Charalambos Antoniades, David J Ahern, Zhichao Ai, Mark Ainsworth, Chris Allan, Alice Allcock, Brian Angus, M Azim Ansari, Carolina Arancibia-Cárcamo, Dominik Aschenbrenner, Moustafa Attar, J Kenneth Baillie, Eleanor Barnes, Rachael Bashford-Rogers, Archana Bashyal, Sally Beer, Georgina Berridge, Amy Beveridge, Sagida Bibi, Tihana Bicanic, Luke Blackwell, Paul Bowness, Andrew Brent, Andrew Brown, John Broxholme, David Buck, Helen Byrne, Susana Camara, Ivan Candido Ferreira, Philip Charles, Wentao Chen, Yi-Ling Chen, Amanda Chong, Elizabeth Clutterbuck, Mark Coles, Christopher Conlon, Richard Cornall, Adam Cribbs, Fabiola Curion, Emma Davenport, Neil Davidson, Simon Davis, Calliope Dendrou, Julie Dequaire, Lea Dib, James Docker, Christina Dold, Tao Dong, Damien Downes, Hal Drakesmith, Susanna Dunachie, David Duncan, Chris Eijsbouts, Robert Esnouf, Alexis Espinosa, Rachel Etherington, Benjamin Fairfax, Rory Fairhead, Hai Fang, Shayan Fassih, Sally Felle, Maria Fernandez Mendoza, Ricardo Ferreira, Roman Fischer, Thomas Foord, Aden Forrow, John Frater, Anastasia Fries, Veronica Gallardo Sanchez, Lucy Garner, Clementine Geeves, Dominique Georgiou, Leila Godfrey, Tanya Golubchik, Maria Gomez Vazquez, Angie Green, Hong Harper, Heather Harrington, Raphael Heilig, Svenja Hester, Jennifer Hill, Charles Hinds, Clare Hird, Renee Hoekzema, Benjamin Hollis, Jim Hughes, Paula Hutton, Matthew Jackson-Wood, Ashwin Jainarayanan, Anna James-Bott, Kathrin Jansen, Katie Jeffery, Elizabeth Jones, Luke Jostins, Georgina Kerr, David Kim, Paul Klenerman, Vinod Kumar, Piyush Kumar Sharma, Prathiba Kurupati, Andrew Kwok, Angela Lee, Aline Linder, Teresa Lockett, Lorne Lonie, Maria Lopopolo, Martyna Lukoseviciute, Jian Luo, Spyridoula Marinou, Brian Marsden, Jose Martinez, Philippa Matthews, Michalina Mazurczyk, Simon McGowan, Stuart McKechnie, Adam Mead, Yuxin Mi, Claudia Monaco, Ruddy Montadon, Giorgio Napolitani, Isar Nassiri, Alex Novak, Darragh O'Brien, Daniel O'Connor, Denise O'Donnell, Graham Ogg, Lauren Overend, Inhye Park, Ian Pavord, Yanchun Peng, Frank Penkava, Mariana Pereira Pinho, Elena Perez, Andrew Pollard, Fiona Powrie, Bethan Psaila, T Phuong Quan, Emmanouela Repapi, Santiago Revale, Laura Silva-Reyes, Jean-Baptiste Richard, Charlotte Rich-Griffin, Thomas Ritter, Christine Rollier, Matthew Rowland, Fabian Ruehle, Mariolina Salio, Stephen Nicholas Sansom, Raphael Sanches Peres, Alberto Santos Delgado, Tatjana Sauka-Spengler, Ron Schwessinger, Giuseppe Scozzafava, Gavin Screaton, Anna Seigal, Malcolm Semple, Martin Sergeant, Christina Simoglou Karali, David Sims, Donal Skelly, Hubert Slawinski, Alberto Sobrinodiaz, Nikolaos Sousos, Lizzie Stafford, Lisa Stockdale, Marie Strickland, Otto Sumray, Bo Sun, Chelsea Taylor, Stephen Taylor, Adan Taylor, Supat Thongjuea, Hannah Thraves, John Todd, Adriana Tomic, Orion Tong, Amy Trebes, Dominik Trzupek, Felicia Anna Tucci, Lance Turtle, Irina Udalova, Holm Uhlig, Erinke van Grinsven, Iolanda Vendrell, Marije Verheul, Alexandru Voda, Guanlin Wang, Lihui Wang, Dapeng Wang, Peter Watkinson, Robert Watson, Michael Weinberger, Justin Whalley, Lorna Witty, Katherine Wray, Luzheng Xue, Hing Yuen Yeung, Zixi Yin, Rebecca Young, Jonathan Youngs, Ping Zhang, Yasemin-Xiomara Zurke, Adrian Banning, Alexios Antonopoulos, Andrew Kelion, Attila Kardos, Benjamin Hudson, Bon-Kwon Koo, Christos Kotanidis, Ciara Mahon, Colin Berry, David Newby, Derek Connolly, Diane Scaletta, Ed Nicol, Elisa McAlindon, Evangelos Oikonomou, Francesca Pugliese, Gianluca Pontone, Giulia Benedetti, Guo-Wei He, Henry West, Hidekazu Kondo, Imre Benedek, Intrajeet Das, John Graby, John Greenwood, Jonathan Rodrigues, Junbo Ge, Keith Channon, Larissa Fabritz, Li-Juan Fan, Lucy Kingham, Marco Guglielmo, Matthias Schmitt, Meinrad Beer, Michelle Anderson, Milind Desai, Mohamed Marwan, Naohiko Takahashi, Nehal Mehta, Neng Dai, Nicholas Screaton, Nikant Sabharwal, Pál Maurovich-Horvat, Rajesh Kharbanda, Rebecca Preston, Richard Wood, Ron Blankstein, Ronak Rajani, Saeed Mirsadraee, Shahzad Munir, Steffen Klömpken, Steffen Petersen, Stephan Achenbach, Susan Anthony, Sze Mak, Tarun Mittal, Theodora Benedek, Vinoda Sharma, and Wen-Hua Lin
Subjects: Inflammation, SARS-CoV-2, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Angiography, Medicine (miscellaneous), COVID-19, Health Informatics, State Medicine, Health Information Management, Artificial Intelligence, Cytokines, Humans, Decision Sciences (miscellaneous), Prospective Studies, Tomography, X-Ray Computed
Abstract: Contains fulltext : 286832.pdf (Publisher’s version ) (Open Access) BACKGROUND: Direct evaluation of vascular inflammation in patients with COVID-19 would facilitate more efficient trials of new treatments and identify patients at risk of long-term complications who might respond to treatment. We aimed to develop a novel artificial intelligence (AI)-assisted image analysis platform that quantifies cytokine-driven vascular inflammation from routine CT angiograms, and sought to validate its prognostic value in COVID-19. METHODS: For this prospective outcomes validation study, we developed a radiotranscriptomic platform that uses RNA sequencing data from human internal mammary artery biopsies to develop novel radiomic signatures of vascular inflammation from CT angiography images. We then used this platform to train a radiotranscriptomic signature (C19-RS), derived from the perivascular space around the aorta and the internal mammary artery, to best describe cytokine-driven vascular inflammation. The prognostic value of C19-RS was validated externally in 435 patients (331 from study arm 3 and 104 from study arm 4) admitted to hospital with or without COVID-19, undergoing clinically indicated pulmonary CT angiography, in three UK National Health Service (NHS) trusts (Oxford, Leicester, and Bath). We evaluated the diagnostic and prognostic value of C19-RS for death in hospital due to COVID-19, did sensitivity analyses based on dexamethasone treatment, and investigated the correlation of C19-RS with systemic transcriptomic changes. FINDINGS: Patients with COVID-19 had higher C19-RS than those without (adjusted odds ratio [OR] 2·97 [95% CI 1·43-6·27], p=0·0038), and those infected with the B.1.1.7 (alpha) SARS-CoV-2 variant had higher C19-RS values than those infected with the wild-type SARS-CoV-2 variant (adjusted OR 1·89 [95% CI 1·17-3·20] per SD, p=0·012). C19-RS had prognostic value for in-hospital mortality in COVID-19 in two testing cohorts (high [≥6·99] vs low [
Published: 2022

10. Divergent trajectories of antiviral memory after SARS-CoV-2 infection

Author: Adriana, Tomic, Donal T, Skelly, Ane, Ogbe, Daniel, O'Connor, Matthew, Pace, Emily, Adland, Frances, Alexander, Mohammad, Ali, Kirk, Allott, M, Azim Ansari, Sandra, Belij-Rammerstorfer, Sagida, Bibi, Luke, Blackwell, Anthony, Brown, Helen, Brown, Breeze, Cavell, Elizabeth A, Clutterbuck, Thushan, de Silva, David, Eyre, Sheila, Lumley, Amy, Flaxman, James, Grist, Carl-Philipp, Hackstein, Rachel, Halkerston, Adam C, Harding, Jennifer, Hill, Tim, James, Cecilia, Jay, Síle A, Johnson, Barbara, Kronsteiner, Yolanda, Lie, Aline, Linder, Stephanie, Longet, Spyridoula, Marinou, Philippa C, Matthews, Jack, Mellors, Christos, Petropoulos, Patpong, Rongkard, Cynthia, Sedik, Laura, Silva-Reyes, Holly, Smith, Lisa, Stockdale, Stephen, Taylor, Stephen, Thomas, Timothy, Tipoe, Lance, Turtle, Vinicius Adriano, Vieira, Terri, Wrin, Andrew J, Pollard, Teresa, Lambe, Chris P, Conlon, Katie, Jeffery, Simon, Travis, Philip, Goulder, John, Frater, Alex J, Mentzer, Lizzie, Stafford, Miles W, Carroll, William S, James, Paul, Klenerman, Eleanor, Barnes, Christina, Dold, Nick P, Talbot, Group, OPTIC Clinical, and Group, PITCH Study
Subjects: Multidisciplinary, SARS-CoV-2, Spike Glycoprotein, Coronavirus, COVID-19, Humans, General Physics and Astronomy, Longitudinal Studies, General Chemistry, Antibodies, Viral, Antiviral Agents, General Biochemistry, Genetics and Molecular Biology
Abstract: The trajectories of acquired immunity to severe acute respiratory syndrome coronavirus 2 infection are not fully understood. We present a detailed longitudinal cohort study of UK healthcare workers prior to vaccination, presenting April-June 2020 with asymptomatic or symptomatic infection. Here we show a highly variable range of responses, some of which (T cell interferon-gamma ELISpot, N-specific antibody) wane over time, while others (spike-specific antibody, B cell memory ELISpot) are stable. We use integrative analysis and a machine-learning approach (SIMON - Sequential Iterative Modeling OverNight) to explore this heterogeneity. We identify a subgroup of participants with higher antibody responses and interferon-gamma ELISpot T cell responses, and a robust trajectory for longer term immunity associates with higher levels of neutralising antibodies against the infecting (Victoria) strain and also against variants B.1.1.7 (alpha) and B.1.351 (beta). These variable trajectories following early priming may define subsequent protection from severe disease from novel variants.
Published: 2022

11. Divergent trajectories of antiviral memory after SARS-Cov-2 infection

Author: Adriana Tomic, Donal T. Skelly, Ane Ogbe, Daniel O'Connor, Matthew Pace, Emily Adland, Frances Alexander, Mohammad Ali, Kirk Allott, M. Azim Ansari, null Sandra Belij-Rammerstorfer, Sagida Bibi, Luke Blackwell, Anthony Brown, Helen Brown, Breeze Cavell, Elizabeth A. Clutterbuck, Thushan I de Silva, David Eyre, null Amy Flaxman, James Grist, Carl-Philipp Hackstein, null Rachel Halkerston, Adam C. Harding, Jennifer Hill, Tim James, null Cecilia Jay, Síle A. Johnson, Barbara Kronsteiner, Yolanda Lie, Aline Linder, Stephanie Longet, Spyridoula Marinou, Philippa C. Matthews, Jack Mellors, Christos Petropoulos, Patpong Rongkard, null Cynthia Sedik, Laura Silva-Reyes, Holly Smith, null Lisa Stockdale, Stephen Taylor, Stephen Thomas, Timothy Tipoe, Lance Turtle, Vinicius Adriano Vieira, null Terri Wrin, OPTIC Clinical Group, PITCH Study Group, C-MORE Group, Andrew J. Pollard, Teresa Lambe, null Christopher P. Conlon, Katie Jeffery, Simon Travis, Philip J. Goulder, John Frater, Alexander J. Mentzer, Lizzie Stafford, Miles W. Carroll, William S. James, Paul Klenerman, Eleanor Barnes, Christina Dold, and Susanna J. Dunachie
Subjects: biology, business.industry, ELISPOT, T cell, Antiviral antibody, Acquired immune system, Vaccination, Immune system, medicine.anatomical_structure, Immunity, Immunology, biology.protein, medicine, Antibody, business
Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is normally controlled by effective host immunity including innate, humoral and cellular responses. However, the trajectories and correlates of acquired immunity, and the capacity of memory responses months after infection to neutralise variants of concern - which has important public health implications - is not fully understood. To address this, we studied a cohort of 78 UK healthcare workers who presented in April to June 2020 with symptomatic PCR-confirmed infection or who tested positive during an asymptomatic screening programme and tracked virus-specific B and T cell responses longitudinally at 5-6 time points each over 6 months, prior to vaccination. We observed a highly variable range of responses, some of which - T cell interferon-gamma (IFN-γ) ELISpot, N-specific antibody waned over time across the cohort, while others (spike-specific antibody, B cell memory ELISpot) were stable. In such cohorts, antiviral antibody has been linked to protection against re-infection. We used integrative analysis and a machine-learning approach (SIMON - Sequential Iterative Modeling Over Night) to explore this heterogeneity and to identify predictors of sustained immune responses. Hierarchical clustering defined a group of high and low antibody responders, which showed stability over time regardless of clinical presentation. These antibody responses correlated with IFN-γ ELISpot measures of T cell immunity and represent a subgroup of patients with a robust trajectory for longer term immunity. Importantly, this immune-phenotype associates with higher levels of neutralising antibodies not only against the infecting (Victoria) strain but also against variants B.1.1.7 (alpha) and B.1.351 (beta). Overall memory responses to SARS-CoV-2 show distinct trajectories following early priming, that may define subsequent protection against infection and severe disease from novel variants.* These authors contributed equally.# These authors jointly supervised this work and contributed equally.Corresponding authors: Eleanor Barnes, email: ellie.barnes@ndm.ox.ac.ukand Adriana Tomic, email: 19info@adrianatomic.com
Published: 2021

12. MCMV based vaccine vectors expressing full-length viral proteins provide long-term humoral immune protection upon a single-shot vaccination

Author: Carlos A. Guzmán, Federico Bertoglio, Bar-On Y, Boehme J, Pöhlmann S, Martin Messerle, Kathrin Eschke, Luka Cicin-Sain, Adriana Tomic, Zheng X, Stephan Ludwig, Chaudhry Mz, Michael Hust, Ofer Mandelboim, Kim Y, Linda Brunotte, Stipan Jonjić, Ebensen T, Hoffmann M, and Bruder D
Subjects: Vaccination, Immune protection, Single shot, virus diseases, Biology, Virology, Term (time)
Abstract: Global pandemics by influenza or coronaviruses cause severe disruptions to the public health and lead to severe morbidity and mortality. Vaccines against these pathogens remain a medical need. CMV (cytomegalovirus) is a β-herpesvirus that induces uniquely robust immune responses, where outstandingly large populations of antigen-specific CD8+ T cells are maintained for a lifetime. Hence, CMV has been proposed and investigated as a novel vaccine vector expressing antigenic peptides or proteins to elicit protective cellular immune responses against numerous pathogens. We generated two recombinant murine CMV (MCMV) vaccine vectors expressing the hemagglutinin (HA) of influenza A virus (MCMVHA) or the spike protein of the severe acute respiratory syndrome coronavirus 2 (MCMVS). A single shot of MCMVs expressing either viral protein induced potent neutralizing antibody responses, which strengthened over time. Importantly, MCMVHA vaccinated mice were protected from illness following challenge with the influenza virus, and we excluded that this protection was due to effects of memory T cells. Conclusively, we show here that MCMV vectors do not only induce long-term cellular immunity, but also humoral responses that provide long-term immune protection against clinically relevant respiratory pathogens.
Published: 2021

13. A blood atlas of COVID-19 defines hallmarks of disease severity and specificity

Author: David J. Ahern, Zhichao Ai, Mark Ainsworth, Chris Allan, Alice Allcock, Brian Angus, M. Azim Ansari, Carolina V. Arancibia-Cárcamo, Dominik Aschenbrenner, Moustafa Attar, J. Kenneth Baillie, Eleanor Barnes, Rachael Bashford-Rogers, Archana Bashyal, Sally Beer, Georgina Berridge, Amy Beveridge, Sagida Bibi, Tihana Bicanic, Luke Blackwell, Paul Bowness, Andrew Brent, Andrew Brown, John Broxholme, David Buck, Katie L. Burnham, Helen Byrne, Susana Camara, Ivan Candido Ferreira, Philip Charles, Wentao Chen, Yi-Ling Chen, Amanda Chong, Elizabeth A. Clutterbuck, Mark Coles, Christopher P. Conlon, Richard Cornall, Adam P. Cribbs, Fabiola Curion, Emma E. Davenport, Neil Davidson, Simon Davis, Calliope A. Dendrou, Julie Dequaire, Lea Dib, James Docker, Christina Dold, Tao Dong, Damien Downes, Hal Drakesmith, Susanna J. Dunachie, David A. Duncan, Chris Eijsbouts, Robert Esnouf, Alexis Espinosa, Rachel Etherington, Benjamin Fairfax, Rory Fairhead, Hai Fang, Shayan Fassih, Sally Felle, Maria Fernandez Mendoza, Ricardo Ferreira, Roman Fischer, Thomas Foord, Aden Forrow, John Frater, Anastasia Fries, Veronica Gallardo Sanchez, Lucy C. Garner, Clementine Geeves, Dominique Georgiou, Leila Godfrey, Tanya Golubchik, Maria Gomez Vazquez, Angie Green, Hong Harper, Heather A. Harrington, Raphael Heilig, Svenja Hester, Jennifer Hill, Charles Hinds, Clare Hird, Ling-Pei Ho, Renee Hoekzema, Benjamin Hollis, Jim Hughes, Paula Hutton, Matthew A. Jackson-Wood, Ashwin Jainarayanan, Anna James-Bott, Kathrin Jansen, Katie Jeffery, Elizabeth Jones, Luke Jostins, Georgina Kerr, David Kim, Paul Klenerman, Julian C. Knight, Vinod Kumar, Piyush Kumar Sharma, Prathiba Kurupati, Andrew Kwok, Angela Lee, Aline Linder, Teresa Lockett, Lorne Lonie, Maria Lopopolo, Martyna Lukoseviciute, Jian Luo, Spyridoula Marinou, Brian Marsden, Jose Martinez, Philippa C. Matthews, Michalina Mazurczyk, Simon McGowan, Stuart McKechnie, Adam Mead, Alexander J. Mentzer, Yuxin Mi, Claudia Monaco, Ruddy Montadon, Giorgio Napolitani, Isar Nassiri, Alex Novak, Darragh P. O'Brien, Daniel O'Connor, Denise O'Donnell, Graham Ogg, Lauren Overend, Inhye Park, Ian Pavord, Yanchun Peng, Frank Penkava, Mariana Pereira Pinho, Elena Perez, Andrew J. Pollard, Fiona Powrie, Bethan Psaila, T. Phuong Quan, Emmanouela Repapi, Santiago Revale, Laura Silva-Reyes, Jean-Baptiste Richard, Charlotte Rich-Griffin, Thomas Ritter, Christine S. Rollier, Matthew Rowland, Fabian Ruehle, Mariolina Salio, Stephen Nicholas Sansom, Raphael Sanches Peres, Alberto Santos Delgado, Tatjana Sauka-Spengler, Ron Schwessinger, Giuseppe Scozzafava, Gavin Screaton, Anna Seigal, Malcolm G. Semple, Martin Sergeant, Christina Simoglou Karali, David Sims, Donal Skelly, Hubert Slawinski, Alberto Sobrinodiaz, Nikolaos Sousos, Lizzie Stafford, Lisa Stockdale, Marie Strickland, Otto Sumray, Bo Sun, Chelsea Taylor, Stephen Taylor, Adan Taylor, Supat Thongjuea, Hannah Thraves, John A. Todd, Adriana Tomic, Orion Tong, Amy Trebes, Dominik Trzupek, Felicia Anna Tucci, Lance Turtle, Irina Udalova, Holm Uhlig, Erinke van Grinsven, Iolanda Vendrell, Marije Verheul, Alexandru Voda, Guanlin Wang, Lihui Wang, Dapeng Wang, Peter Watkinson, Robert Watson, Michael Weinberger, Justin Whalley, Lorna Witty, Katherine Wray, Luzheng Xue, Hing Yuen Yeung, Zixi Yin, Rebecca K. Young, Jonathan Youngs, Ping Zhang, Yasemin-Xiomara Zurke, Cribbs, AP, and Consortium, COvid-19 Multi-omics Blood ATlas (COMBAT)
Subjects: Resource, Adult, Male, Myeloid, Proteome, coronavirus, Cell Cycle Proteins, Disease, Severity of Illness Index, General Biochemistry, Genetics and Molecular Biology, Monocytes, Sepsis, Machine Learning, Mitogen-Activated Protein Kinase 14, transcriptomics, Immune system, proteomics, blood, Influenza, Human, medicine, Humans, Lymphocytes, Progenitor cell, Principal Component Analysis, epigenetics, business.industry, SARS-CoV-2, Clinical study design, Acute-phase protein, COVID-19, personalized medicine, Blood Proteins, multi-omics, Middle Aged, medicine.disease, Coronavirus, Transcription Factor AP-1, medicine.anatomical_structure, Drug development, Immunology, Female, immune, business, Biomarkers
Abstract: Treatment of severe COVID-19 is currently limited by clinical heterogeneity and incomplete description of specific immune biomarkers. We present here a comprehensive multi-omic blood atlas for patients with varying COVID-19 severity in an integrated comparison with influenza and sepsis patients versus healthy volunteers. We identify immune signatures and correlates of host response. Hallmarks of disease severity involved cells, their inflammatory mediators and networks, including progenitor cells and specific myeloid and lymphocyte subsets, features of the immune repertoire, acute phase response, metabolism and coagulation. Persisting immune activation involving AP-1/p38MAPK was a specific feature of COVID-19. The plasma proteome enabled sub-phenotyping into patient clusters, predictive of severity and outcome. Systems-based integrative analyses including tensor and matrix decomposition of all modalities revealed feature groupings linked with severity and specificity compared to influenza and sepsis. Our approach and blood atlas will support future drug development, clinical trial design and personalized medicine approaches for COVID-19., Graphical Abstract, A multi-omic analysis of patient blood samples reveals both similarities and specific features of COVID-19 when compared with samples obtained from sepsis or influenza patients which could yield better targetted therapies for severe COVID-19.
Published: 2021

14. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

Author: Merryn Voysey, Sue Ann Costa Clemens, Shabir A Madhi, Lily Y Weckx, Pedro M Folegatti, Parvinder K Aley, Brian Angus, Vicky L Baillie, Shaun L Barnabas, Qasim E Bhorat, Sagida Bibi, Carmen Briner, Paola Cicconi, Andrea M Collins, Rachel Colin-Jones, Clare L Cutland, Thomas C Darton, Keertan Dheda, Christopher J A Duncan, Katherine R W Emary, Katie J Ewer, Lee Fairlie, Saul N Faust, Shuo Feng, Daniela M Ferreira, Adam Finn, Anna L Goodman, Catherine M Green, Christopher A Green, Paul T Heath, Catherine Hill, Helen Hill, Ian Hirsch, Susanne H C Hodgson, Alane Izu, Susan Jackson, Daniel Jenkin, Carina C D Joe, Simon Kerridge, Anthonet Koen, Gaurav Kwatra, Rajeka Lazarus, Alison M Lawrie, Alice Lelliott, Vincenzo Libri, Patrick J Lillie, Raburn Mallory, Ana V A Mendes, Eveline P Milan, Angela M Minassian, Alastair McGregor, Hazel Morrison, Yama F Mujadidi, Anusha Nana, Peter J O’Reilly, Sherman D Padayachee, Ana Pittella, Emma Plested, Katrina M Pollock, Maheshi N Ramasamy, Sarah Rhead, Alexandre V Schwarzbold, Nisha Singh, Andrew Smith, Rinn Song, Matthew D Snape, Eduardo Sprinz, Rebecca K Sutherland, Richard Tarrant, Emma C Thomson, M Estée Török, Mark Toshner, David P J Turner, Johan Vekemans, Tonya L Villafana, Marion E E Watson, Christopher J Williams, Alexander D Douglas, Adrian V S Hill, Teresa Lambe, Sarah C Gilbert, Andrew J Pollard, Marites Aban, Fatola Abayomi, Kushala Abeyskera, Jeremy Aboagye, Matthew Adam, Kirsty Adams, James Adamson, Yemi A. Adelaja, Gbadebo Adewetan, Syed Adlou, Khatija Ahmed, Yasmeen Akhalwaya, Saajida Akhalwaya, Andrew Alcock, Aabidah Ali, Elizabeth R. Allen, Lauren Allen, Thamires C. D. S. C Almeida, Mariana P.S. Alves, Fabio Amorim, Foteini Andritsou, Rachel Anslow, Matthew Appleby, Edward H. Arbe-Barnes, Mark P. Ariaans, Beatriz Arns, Laiana Arruda, Paula Azi, Lorena Azi, Gavin Babbage, Catherine Bailey, Kenneth F. Baker, Megan Baker, Natalie Baker, Philip Baker, Lisa Baldwin, Ioana Baleanu, Danieli Bandeira, Anna Bara, Marcella A.S. Barbosa, Debbie Barker, Gavin D. Barlow, Eleanor Barnes, Andrew S. Barr, Jordan R. Barrett, Jessica Barrett, Louise Bates, Alexander Batten, Kirsten Beadon, Emily Beales, Rebecca Beckley, Sandra Belij-Rammerstorfer, Jonathan Bell, Duncan Bellamy, Nancy Bellei, Sue Belton, Adam Berg, Laura Bermejo, Eleanor Berrie, Lisa Berry, Daniella Berzenyi, Amy Beveridge, Kevin R. Bewley, Helen Bexhell, Sutika Bhikha, Asad E. Bhorat, Zaheda E. Bhorat, Else Bijker, Geeta Birch, Sarah Birch, Adam Bird, Olivia Bird, Karen Bisnauthsing, Mustapha Bittaye, Katherine Blackstone, Luke Blackwell, Heather Bletchly, Caitlin L. Blundell, Susannah R. Blundell, Pritesh Bodalia, Bruno C. Boettger, Emma Bolam, Elena Boland, Daan Bormans, Nicola Borthwick, Francesca Bowring, Amy Boyd, Penny Bradley, Tanja Brenner, Phillip Brown, Claire Brown, Charlie Brown-O'Sullivan, Scott Bruce, Emily Brunt, Ruaridh Buchan, William Budd, Yusuf A. Bulbulia, Melanie Bull, Jamie Burbage, Hassan Burhan, Aileen Burn, Karen R. Buttigieg, Nicholas Byard, Ingrid Cabera Puig, Gloria Calderon, Anna Calvert, Susana Camara, Michelangelo Cao, Federica Cappuccini, João R. Cardoso, Melanie Carr, Miles W. Carroll, Andrew Carson-Stevens, Yasmin de M. Carvalho, José A.M. Carvalho, Helen R. Casey, Paul Cashen, Thais Castro, Lucia Carratala Castro, Katrina Cathie, Ana Cavey, José Cerbino-Neto, Jim Chadwick, David Chapman, Sue Charlton, Irina Chelysheva, Oliver Chester, Sunder Chita, Jee-Sun Cho, Liliana Cifuentes, Elizabeth Clark, Matthew Clark, Andrea Clarke, Elizabeth A. Clutterbuck, Sarah L.K. Collins, Christopher P. Conlon, Sean Connarty, Naomi Coombes, Cushla Cooper, Rachel Cooper, Lynne Cornelissen, Tumena Corrah, Catherine Cosgrove, Tony Cox, Wendy E.M. Crocker, Sarah Crosbie, Lorraine Cullen, Dan Cullen, Debora R.M.F. Cunha, Christina Cunningham, Fiona C. Cuthbertson, Suzete N. Farias Da Guarda, Larissa P. da Silva, Brad E. Damratoski, Zsofia Danos, Maria T.D.C. Dantas, Paula Darroch, Mehreen S. Datoo, Chandrabali Datta, Malika Davids, Sarah L. Davies, Hannah Davies, Elizabeth Davis, Judith Davis, John Davis, Maristela M.D. De Nobrega, Lis Moreno De Oliveira Kalid, David Dearlove, Tesfaye Demissie, Amisha Desai, Stefania Di Marco, Claudio Di Maso, Maria I.S. Dinelli, Tanya Dinesh, Claire Docksey, Christina Dold, Tao Dong, Francesca R. Donnellan, Tannyth Dos Santos, Thainá G. dos Santos, Erika Pachecho Dos Santos, Naomi Douglas, Charlotte Downing, Jonathan Drake, Rachael Drake-Brockman, Kimberley Driver, Ruth Drury, Susanna J. Dunachie, Benjamin S. Durham, Lidiana Dutra, Nicholas J.W. Easom, Samual van Eck, Mandy Edwards, Nick J. Edwards, Omar M. El Muhanna, Sean C. Elias, Mike Elmore, Marcus English, Alisgair Esmail, Yakub Moosa Essack, Eoghan Farmer, Mutjaba Farooq, Madi Farrar, Leonard Farrugia, Beverley Faulkner, Sofiya Fedosyuk, Sally Felle, Carla Ferreira Da Silva, Samantha Field, Richard Fisher, Amy Flaxman, James Fletcher, Hazel Fofie, Henry Fok, Karen J. Ford, Jamie Fowler, Pedro H.A. Fraiman, Emma Francis, Marilia M. Franco, John Frater, Marilúcia S.M. Freire, Samantha H. Fry, Sabrina Fudge, Julie Furze, Michelle Fuskova, Pablo Galian-Rubio, Eva Galiza, Harriet Garlant, Madita Gavrila, Ailsa Geddes, Karyna A. Gibbons, Ciaran Gilbride, Hardeep Gill, Sharon Glynn, Kerry Godwin, Karishma Gokani, Ursula Carvalho Goldoni, Maria Goncalves, Isabela G.S. Gonzalez, Jayne Goodwin, Amina Goondiwala, Katherine Gordon-Quayle, Giacomo Gorini, Janet Grab, Lara Gracie, Melanie Greenland, Nicola Greenwood, Johann Greffrath, Marisa M. Groenewald, Leonardo Grossi, Gaurav Gupta, Mark Hackett, Bassam Hallis, Mainga Hamaluba, Elizabeth Hamilton, Joseph Hamlyn, Daniel Hammersley, Aidan T. Hanrath, Brama Hanumunthadu, Stephanie A. Harris, Clair Harris, Tara Harris, Thomas D. Harrison, Daisy Harrison, Thomas C. Hart, Birgit Hartnell, Shadin Hassan, John Haughney, Sophia Hawkins, Jodie Hay, Ian Head, John Henry, Macarena Hermosin Herrera, David B. Hettle, Jennifer Hill, Gina Hodges, Elizea Horne, Mimi M. Hou, Catherine Houlihan, Elizabeth Howe, Nicola Howell, Jonathan Humphreys, Holly E. Humphries, Katrina Hurley, Claire Huson, Angela Hyder-Wright, Catherine Hyams, Sabina Ikram, Alka Ishwarbhai, Monica Ivan, Poppy Iveson, Vidyashankara Iyer, Frederic Jackson, Jeanne De Jager, Shameem Jaumdally, Helen Jeffers, Natasha Jesudason, Bryony Jones, Kathryn Jones, Elizabeth Jones, Christopher Jones, Marianna Rocha Jorge, Aylin Jose, Amar Joshi, Eduardo A.M.S. Júnior, Joanne Kadziola, Reshma Kailath, Faeeza Kana, Konstantinos Karampatsas, Mwila Kasanyinga, Jade Keen, Elizabeth J. Kelly, Dearbhla M. Kelly, Debbie Kelly, Sarah Kelly, David Kerr, Renato de Ávila Kfouri, Liaquat Khan, Baktash Khozoee, Sarah Kidd, Annabel Killen, Jasmin Kinch, Patrick Kinch, Lloyd D.W. King, Thomas B. King, Lucy Kingham, Paul Klenerman, Francesca Knapper, Julian C. Knight, Daniel Knott, Stanislava Koleva, Matilda Lang, Gail Lang, Colin W. Larkworthy, Jessica P.J. Larwood, Rebecca Law, Erica M. Lazarus, Amanda Leach, Emily A. Lees, Nana-Marie Lemm, Alvaro Lessa, Stephanie Leung, Yuanyuan Li, Amelia M. Lias, Kostas Liatsikos, Aline Linder, Samuel Lipworth, Shuchang Liu, Xinxue Liu, Adam Lloyd, Stephanie Lloyd, Lisa Loew, Raquel Lopez Ramon, Leandro Lora, Vicki Lowthorpe, Kleber Luz, Jonathan C. MacDonald, Gordon MacGregor, Meera Madhavan, David O. Mainwaring, Edson Makambwa, Rebecca Makinson, Mookho Malahleha, Ross Malamatsho, Garry Mallett, Kushal Mansatta, Takalani Maoko, Katlego Mapetla, Natalie G. Marchevsky, Spyridoula Marinou, Emma Marlow, Gabriela N. Marques, Paula Marriott, Richard P. Marshall, Julia L. Marshall, Flávia J. Martins, Masebole Masenya, Mduduzi Masilela, Shauna K. Masters, Moncy Mathew, Hosea Matlebjane, Kedidimetse Matshidiso, Olga Mazur, Andrea Mazzella, Hugh McCaughan, Joanne McEwan, Joanna McGlashan, Lorna McInroy, Zoe McIntyre, Daniela McLenaghan, Nicky McRobert, Steve McSwiggan, Clare Megson, Savviz Mehdipour, Wilma Meijs, Renata N.Á. Mendonça, Alexander J. Mentzer, Neginsadat Mirtorabi, Celia Mitton, Sibusiso Mnyakeni, Fiona Moghaddas, Kgaogelo Molapo, Mapule Moloi, Maria Moore, M. Isabel Moraes-Pinto, Marni Moran, Ella Morey, Róisín Morgans, Susan Morris, Sheila Morris, Helen C. Morris, Franca Morselli, Gertraud Morshead, Richard Morter, Lynelle Mottal, Andrew Moultrie, Nathifa Moya, Mushiya Mpelembue, Sibekezelo Msomi, Yvonne Mugodi, Ekta Mukhopadhyay, Jilly Muller, Alasdair Munro, Claire Munro, Sarah Murphy, Philomena Mweu, Celia Hatsuko Myasaki, Gurudutt Naik, Kush Naker, Eleni Nastouli, Abida Nazir, Bongani Ndlovu, Fabio Neffa, Cecilia Njenga, Helena Noal, Andrés Noé, Gabrielle Novaes, Fay L. Nugent, Géssika Nunes, Katie O'Brien, Daniel O'Connor, Miranda Odam, Suzette Oelofse, Blanche Oguti, Victoria Olchawski, Neil J. Oldfield, Marianne G. Oliveira, Catarina Oliveira, Angela Oosthuizen, Paula O'Reilly, Piper Osborne, David R.J. Owen, Lydia Owen, Daniel Owens, Nelly Owino, Mihaela Pacurar, Brenda V.B. Paiva, Edna M.F. Palhares, Susan Palmer, Sivapriyai Parkinson, Helena M.R.T. Parracho, Karen Parsons, Dipak Patel, Bhumika Patel, Faeezah Patel, Kelly Patel, Maia Patrick-Smith, Ruth O. Payne, Yanchun Peng, Elizabeth J. Penn, Anna Pennington, Marco Polo Peralta Alvarez, James Perring, Nicola Perry, Rubeshan Perumal, Sahir Petkar, Tricia Philip, Daniel J. Phillips, Jennifer Phillips, Mary Kgomotso Phohu, Lorinda Pickup, Sonja Pieterse, Jo Piper, Dimitra Pipini, Mary Plank, Joan Du Plessis, Samuel Pollard, Jennifer Pooley, Anil Pooran, Ian Poulton, Claire Powers, Fernando B. Presa, David A. Price, Vivien Price, Marcelo Primeira, Pamela C. Proud, Samuel Provstgaard-Morys, Sophie Pueschel, David Pulido, Sheena Quaid, Ria Rabara, Alexandra Radford, Kajal Radia, Durga Rajapaska, Thurkka Rajeswaran, Alberto San Francisco Ramos, Fernando Ramos Lopez, Tommy Rampling, Jade Rand, Helen Ratcliffe, Tom Rawlinson, David Rea, Byron Rees, Jesús Reiné, Mila Resuello-Dauti, Emilia Reyes Pabon, Carla M. Ribiero, Marivic Ricamara, Alex Richter, Neil Ritchie, Adam J. Ritchie, Alexander J. Robbins, Hannah Roberts, Ryan E. Robinson, Hannah Robinson, Talita T. Rocchetti, Beatriz Pinho Rocha, Sophie Roche, Christine Rollier, Louisa Rose, Amy L. Ross Russell, Lindie Rossouw, Simon Royal, Indra Rudiansyah, Sarah Ruiz, Stephen Saich, Claudia Sala, Jessica Sale, Ahmed M. Salman, Natalia Salvador, Stephannie Salvador, Milla Sampaio, Annette D. Samson, Amada Sanchez-Gonzalez, Helen Sanders, Katherine Sanders, Erika Santos, Mayara F.S. Santos Guerra, Iman Satti, Jack E. Saunders, Caroline Saunders, Aakifah Sayed, Ina Schim van der Loeff, Annina B. Schmid, Ella Schofield, Gavin Screaton, Samiullah Seddiqi, Rameswara R. Segireddy, Roberta Senger, Sonia Serrano, Rajiv Shah, Imam Shaik, Hannah E. Sharpe, Katherine Sharrocks, Robert Shaw, Adam Shea, Amy Shepherd, James G. Shepherd, Farah Shiham, Emad Sidhom, Sarah E. Silk, Antonio Carlos da Silva Moraes, Gilberto Silva-Junior, Laura Silva-Reyes, Anderson D. Silveira, Mariana B.V. Silveira, Jaisi Sinha, Donal T. Skelly, Daniel C. Smith, Nick Smith, Holly E. Smith, David J. Smith, Catherine C. Smith, Airanuédida Soares, Tiago Soares, Carla Solórzano, Guilherme L. Sorio, Kim Sorley, Tiffany Sosa-Rodriguez, Cinthia M.C.D.L. Souza, Bruno S.D.F. Souza, Alessandra R. Souza, Alexandra J. Spencer, Fernanda Spina, Louise Spoors, Lizzie Stafford, Imogen Stamford, Igor Starinskij, Ricardo Stein, Jill Steven, Lisa Stockdale, Lisa V. Stockwell, Louise H. Strickland, Arabella C. Stuart, Ann Sturdy, Natalina Sutton, Anna Szigeti, Abdessamad Tahiri-Alaoui, Rachel Tanner, Carol Taoushanis, Alexander W. Tarr, Keja Taylor, Ursula Taylor, Iona Jennifer Taylor, Justin Taylor, Rebecca te Water Naude, Yrene Themistocleous, Andreas Themistocleous, Merin Thomas, Kelly Thomas, Tonia M. Thomas, Asha Thombrayil, Fawziyah Thompson, Amber Thompson, Kevin Thompson, Ameeka Thompson, Julia Thomson, Viv Thornton-Jones, Patrick J. Tighe, Lygia Accioly Tinoco, Gerlynn Tiongson, Bonolo Tladinyane, Michele Tomasicchio, Adriana Tomic, Susan Tonks, James Towner, Nguyen Tran, Julia Tree, Gerry Trillana, Charlotte Trinham, Rose Trivett, Adam Truby, Betty Lebogang Tsheko, Aadil Turabi, Richard Turner, Cheryl Turner, Marta Ulaszewska, Benjamin R. Underwood, Rachel Varughese, Dennis Verbart, Marije Verheul, Iason Vichos, Taiane Vieira, Claire S. Waddington, Laura Walker, Erica Wallis, Matthew Wand, Deborah Warbick, Theresa Wardell, George Warimwe, Sarah C. Warren, Bridget Watkins, Ekaterina Watson, Stewart Webb, Alice Webb-Bridges, Angela Webster, Jessica Welch, Jeanette Wells, Alison West, Caroline White, Rachel White, Paul Williams, Rachel L. Williams, Rebecca Winslow, Mark Woodyer, Andrew T. Worth, Danny Wright, Marzena Wroblewska, Andy Yao, Rafael Zimmer, Dalila Zizi, Peter Zuidewind, Group, Oxford COVID Vaccine Trial, Toshner, Mark [0000-0002-3969-6143], and Apollo - University of Cambridge Repository
Subjects: Male, COVID-19/prevention & control, 030204 cardiovascular system & hematology, law.invention, South Africa, 0302 clinical medicine, Randomized controlled trial, law, Oxford COVID Vaccine Trial Group, wc_505, Single-Blind Method, 030212 general & internal medicine, Young adult, 11 Medical and Health Sciences, wa_105, Covid19, General Medicine, Articles, Middle Aged, Treatment Outcome, Cohort, Perspective, Female, Brazil, Adult, medicine.medical_specialty, COVID-19 Vaccines, Adolescent, qw_806, qw_805, 03 medical and health sciences, Young Adult, Double-Blind Method, Conjugate vaccine, Internal medicine, General & Internal Medicine, ChAdOx1 nCoV-19, medicine, Humans, Adverse effect, Aged, business.industry, SARS-CoV-2, COVID-19, Viral Vaccines, Vaccine efficacy, Interim analysis, United Kingdom, Clinical trial, bf023de6, business, COVID-19 Vaccines/adverse effects
Abstract: BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. \ud \ud \ud METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. \ud \ud \ud FINDINGS: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. \ud \ud \ud INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. \ud \ud \ud FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca.
Published: 2020

15. Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2/3 trial

Author: Maheshi N Ramasamy, Angela M Minassian, Katie J Ewer, Amy L Flaxman, Pedro M Folegatti, Daniel R Owens, Merryn Voysey, Parvinder K Aley, Brian Angus, Gavin Babbage, Sandra Belij-Rammerstorfer, Lisa Berry, Sagida Bibi, Mustapha Bittaye, Katrina Cathie, Harry Chappell, Sue Charlton, Paola Cicconi, Elizabeth A Clutterbuck, Rachel Colin-Jones, Christina Dold, Katherine R W Emary, Sofiya Fedosyuk, Michelle Fuskova, Diane Gbesemete, Catherine Green, Bassam Hallis, Mimi M Hou, Daniel Jenkin, Carina C D Joe, Elizabeth J Kelly, Simon Kerridge, Alison M Lawrie, Alice Lelliott, May N Lwin, Rebecca Makinson, Natalie G Marchevsky, Yama Mujadidi, Alasdair P S Munro, Mihaela Pacurar, Emma Plested, Jade Rand, Thomas Rawlinson, Sarah Rhead, Hannah Robinson, Adam J Ritchie, Amy L Ross-Russell, Stephen Saich, Nisha Singh, Catherine C Smith, Matthew D Snape, Rinn Song, Richard Tarrant, Yrene Themistocleous, Kelly M Thomas, Tonya L Villafana, Sarah C Warren, Marion E E Watson, Alexander D Douglas, Adrian V S Hill, Teresa Lambe, Sarah C Gilbert, Saul N Faust, Andrew J Pollard, Jeremy Aboagye, Kelly Adams, Aabidah Ali, Elizabeth R. Allen, Lauren Allen, Jennifer L. Allison, Foteini Andritsou, Rachel Anslow, Edward H. Arbe-Barnes, Megan Baker, Natalie Baker, Philip Baker, Ioana Baleanu, Debbie Barker, Eleanor Barnes, Jordan R. Barrett, Kelly Barrett, Louise Bates, Alexander Batten, Kirsten Beadon, Rebecca Beckley, Duncan Bellamy, Adam Berg, Laura Bermejo, Eleanor Berrie, Amy Beveridge, Kevin Bewley, Else M. Bijker, Geeta Birch, Luke Blackwell, Heather Bletchly, Caitlin L. Blundell, Susannah R. Blundell, Emma Bolam, Elena Boland, Daan Bormans, Nicola Borthwick, Konstantinos Boukas, Thomas Bower, Francesca Bowring, Amy Boyd, Tanja Brenner, Phillip Brown, Charlie Brown-O'Sullivan, Scott Bruce, Emily Brunt, Jamie Burbage, Joshua Burgoyne, Karen R. Buttigieg, Nicholas Byard, Ingrid Cabera Puig, Susana Camara, Michelangelo Cao, Federica Cappuccini, Melanie Carr, Miles W. Carroll, Paul Cashen, Ana Cavey, Jim Chadwick, Ruth Challis, David Chapman, David Charles, Irina Chelysheva, Jee-Sun Cho, Liliana Cifuentes, Elizabeth Clark, Sarah Collins, Christopher P. Conlon, Naomi S. Coombes, Rachel Cooper, Cushla Cooper, Wendy E.M. Crocker, Sarah Crosbie, Dan Cullen, Christina Cunningham, Fiona Cuthbertson, Brad E. Datoo, Lynne Dando, Mehreen S. Datoo, Chandrabali Datta, Hannah Davies, Sarah Davies, Elizabeth J. Davis, Judith Davis, David Dearlove, Tesfaye Demissie, Stefania Di Marco, Claudio Di Maso, Danielle DiTirro, Claire Docksey, Tao Dong, Francesca R. Donnellan, Naomi Douglas, Charlotte Downing, Jonathan Drake, Rachael Drake-Brockman, Ruth E. Drury, Susanna J. Dunachie, Christopher J. Edwards, Nick J. Edwards, Omar El Muhanna, Sean C. Elias, Ryan S. Elliott, Michael J. Elmore, Marcus Rex English, Sally Felle, Shuo Feng, Carla Ferreira Da Silva, Samantha Field, Richard Fisher, Carine Fixmer, Karen J. Ford, Jamie Fowler, Emma Francis, John Frater, Julie Furze, Pablo Galian-Rubio, Celine Galloway, Harriet Garlant, Madita Gavrila, Felicity Gibbons, Karyna Gibbons, Ciaran Gilbride, Hardeep Gill, Kerry Godwin, Katherine Gordon-Quayle, Giacomo Gorini, Lyndsey Goulston, Caroline Grabau, Lara Gracie, Nichola Graham, Nicola Greenwood, Oliver Griffiths, Gaurav Gupta, Elizabeth Hamilton, Brama Hanumunthadu, Stephanie A. Harris, Tara Harris, Daisy Harrison, Thomas C. Hart, Birgit Hartnell, Louise Haskell, Sophia Hawkins, John Aaron Henry, Macarena Hermosin Herrera, David Hill, Jennifer Hill, Gina Hodges, Susanne H.C. Hodgson, Katie L. Horton, Elizabeth Howe, Nicola Howell, Jessica Howes, Ben Huang, Jonathan Humphreys, Holly E. Humphries, Poppy Iveson, Frederic Jackson, Susan Jackson, Sam Jauregui, Helen Jeffers, Bryony Jones, Christine E. Jones, Elizabeth Jones, Kathryn Jones, Amar Joshi, Reshma Kailath, Jade Keen, Dearbhla M. Kelly, Sarah Kelly, Debbie Kelly, David Kerr, Liaquat Khan, Baktash Khozoee, Annabel Killen, Jasmin Kinch, Lloyd D.W. King, Thomas B. King, Lucy Kingham, Paul Klenerman, Julian C. Knight, Daniel Knott, Stanislava Koleva, Gail Lang, Colin W. Larkworthy, Jessica P.J. Larwood, Rebecca Law, Arlene Lee, Kim Y.N. Lee, Emily A. Lees, Stephanie Leung, Yuanyuan Li, Amelia M. Lias, Aline Linder, Samuel Lipworth, Shuchang Liu, Xinxue Liu, Stephanie Lloyd, Lisa Loew, Raquel Lopez Ramon, Meera Madhavan, David O. Mainwaring, Garry Mallett, Kushal Mansatta, Spyridoula Marinou, Phedra Marius, Emma Marlow, Paula Marriott, Julia L. Marshall, Jane Martin, Shauna Masters, Joanne McEwan, Joanna L. McGlashan, Lorna McInroy, Nicky McRobert, Clare Megson, Alexander J. Mentzer, Neginsadat Mirtorabi, Celia Mitton, Maria Moore, Marni Moran, Ella Morey, Róisín Morgans, Susan J. Morris, Hazel Morrison Morrison, Gertraud Morshead, Richard Morter, Nathifa A. Moya, Ekta Mukhopadhyay, Jilly Muller, Claire Munro, Sarah Murphy, Philomena Mweu, Andrés Noé, Fay L. Nugent, Katie O'Brien, Daniel O'Connor, Blanché Oguti, Victoria Olchawski, Catarina Oliveira, Peter John O'Reilly, Piper Osborne, Lydia Owen, Nelly Owino, Panagiotis Papageorgiou, Helena Parracho, Karen Parsons, Bhumika Patel, Maia Patrick-Smith, Yanchun Peng, Elizabeth J. Penn, Marco Polo Peralta-Alvarez, James Perring, Christos Petropoulos, Daniel J. Phillips, Dimitra Pipini, Samuel Pollard, Ian Poulton, Danny Pratt, Laura Presland, Pamela C. Proud, Samuel Provstgaard-Morys, Sophie Pueschel, David Pulido, Ria Rabara, Kajal Radia, Durga Rajapaska, Fernando Ramos Lopez, Helen Ratcliffe, Sara Rayhan, Byron Rees, Emilia Reyes Pabon, Hannah Roberts, Isla Robertson, Sophie Roche, Christine S. Rollier, Rossana Romani, Zoe Rose, Indra Rudiansyah, Sabeha Sabheha, Stephannie Salvador, Helen Sanders, Katherine Sanders, Iman Satti, Chloe Sayce, Annina B. Schmid, Ella Schofield, Gavin Screaton, Cynthia Sedik, Samiullah Seddiqi, Rameswara R. Segireddy, Beatrice Selby, Imam Shaik, Hannah R. Sharpe, Robert Shaw, Adam Shea, Sarah Silk, Laura Silva-Reyes, Donal T. Skelly, David J. Smith, Daniel C. Smith, Nicholas Smith, Alexandra J. Spencer, Louise Spoors, Elizabeth Stafford, Imogen Stamford, Lisa Stockdale, David Stockley, Lisa V. Stockwell, Matthew Stokes, Louise H. Strickland, Arabella Stuart, Sulaiman Sulaiman, Eloise Summerton, Zoe Swash, Anna Szigeti, Abdessamad Tahiri-Alaoui, Rachel Tanner, Iona Taylor, Keja Taylor, Ursula Taylor, Rebecca te Water Naude, Andreas Themistocleous, Merin Thomas, Tonia M. Thomas, Amber Thompson, Kevin Thompson, Viv Thornton-Jones, Lan Tinh, Adriana Tomic, Susan Tonks, James Towner, Nguyen Tran, Julian A. Tree, Adam Truby, Cheryl Turner, Richard Turner, Marta Ulaszewska, Rachel Varughese, Dennis Verbart, Marije K. Verheul, Iason Vichos, Laura Walker, Matthew E. Wand, Bridget Watkins, Jessica Welch, Alison J. West, Caroline White, Rachel White, Paul Williams, Mark Woodyer, Andrew T. Worth, Daniel Wright, Terri Wrin, Xin Li Yao, Diana-Andreea Zbarcea, and Dalila Zizi
Subjects: Adult, Male, Pediatrics, medicine.medical_specialty, COVID-19 Vaccines, Adolescent, Immunization, Secondary, Department of Error, 030204 cardiovascular system & hematology, law.invention, Young Adult, 03 medical and health sciences, Immunogenicity, Vaccine, 0302 clinical medicine, Randomized controlled trial, law, ChAdOx1 nCoV-19, medicine, Humans, Single-Blind Method, 030212 general & internal medicine, Young adult, Adverse effect, Aged, Aged, 80 and over, Reactogenicity, SARS-CoV-2, business.industry, Age Factors, COVID-19, Articles, General Medicine, Middle Aged, Clinical trial, Vaccination, Regimen, Immunoglobulin G, Cohort, Female, business
Abstract: BACKGROUND: Older adults (aged ≥70 years) are at increased risk of severe disease and death if they develop COVID-19 and are therefore a priority for immunisation should an efficacious vaccine be developed. Immunogenicity of vaccines is often worse in older adults as a result of immunosenescence. We have reported the immunogenicity of a novel chimpanzee adenovirus-vectored vaccine, ChAdOx1 nCoV-19, in young adults, and now describe the safety and immunogenicity of this vaccine in a wider range of participants, including adults aged 70 years and older. METHODS: In this report of the phase 2 component of a single-blind, randomised, controlled, phase 2/3 trial (COV002), healthy adults aged 18 years and older were enrolled at two UK clinical research facilities, in an age-escalation manner, into 18-55 years, 56-69 years, and 70 years and older immunogenicity subgroups. Participants were eligible if they did not have severe or uncontrolled medical comorbidities or a high frailty score (if aged ≥65 years). First, participants were recruited to a low-dose cohort, and within each age group, participants were randomly assigned to receive either intramuscular ChAdOx1 nCoV-19 (2·2 × 1010 virus particles) or a control vaccine, MenACWY, using block randomisation and stratified by age and dose group and study site, using the following ratios: in the 18-55 years group, 1:1 to either two doses of ChAdOx1 nCoV-19 or two doses of MenACWY; in the 56-69 years group, 3:1:3:1 to one dose of ChAdOx1 nCoV-19, one dose of MenACWY, two doses of ChAdOx1 nCoV-19, or two doses of MenACWY; and in the 70 years and older, 5:1:5:1 to one dose of ChAdOx1 nCoV-19, one dose of MenACWY, two doses of ChAdOx1 nCoV-19, or two doses of MenACWY. Prime-booster regimens were given 28 days apart. Participants were then recruited to the standard-dose cohort (3·5-6·5 × 1010 virus particles of ChAdOx1 nCoV-19) and the same randomisation procedures were followed, except the 18-55 years group was assigned in a 5:1 ratio to two doses of ChAdOx1 nCoV-19 or two doses of MenACWY. Participants and investigators, but not staff administering the vaccine, were masked to vaccine allocation. The specific objectives of this report were to assess the safety and humoral and cellular immunogenicity of a single-dose and two-dose schedule in adults older than 55 years. Humoral responses at baseline and after each vaccination until 1 year after the booster were assessed using an in-house standardised ELISA, a multiplex immunoassay, and a live severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) microneutralisation assay (MNA80). Cellular responses were assessed using an ex-vivo IFN-γ enzyme-linked immunospot assay. The coprimary outcomes of the trial were efficacy, as measured by the number of cases of symptomatic, virologically confirmed COVID-19, and safety, as measured by the occurrence of serious adverse events. Analyses were by group allocation in participants who received the vaccine. Here, we report the preliminary findings on safety, reactogenicity, and cellular and humoral immune responses. This study is ongoing and is registered with ClinicalTrials.gov, NCT04400838, and ISRCTN, 15281137. FINDINGS: Between May 30 and Aug 8, 2020, 560 participants were enrolled: 160 aged 18-55 years (100 assigned to ChAdOx1 nCoV-19, 60 assigned to MenACWY), 160 aged 56-69 years (120 assigned to ChAdOx1 nCoV-19: 40 assigned to MenACWY), and 240 aged 70 years and older (200 assigned to ChAdOx1 nCoV-19: 40 assigned to MenACWY). Seven participants did not receive the boost dose of their assigned two-dose regimen, one participant received the incorrect vaccine, and three were excluded from immunogenicity analyses due to incorrectly labelled samples. 280 (50%) of 552 analysable participants were female. Local and systemic reactions were more common in participants given ChAdOx1 nCoV-19 than in those given the control vaccine, and similar in nature to those previously reported (injection-site pain, feeling feverish, muscle ache, headache), but were less common in older adults (aged ≥56 years) than younger adults. In those receiving two standard doses of ChAdOx1 nCoV-19, after the prime vaccination local reactions were reported in 43 (88%) of 49 participants in the 18-55 years group, 22 (73%) of 30 in the 56-69 years group, and 30 (61%) of 49 in the 70 years and older group, and systemic reactions in 42 (86%) participants in the 18-55 years group, 23 (77%) in the 56-69 years group, and 32 (65%) in the 70 years and older group. As of Oct 26, 2020, 13 serious adverse events occurred during the study period, none of which were considered to be related to either study vaccine. In participants who received two doses of vaccine, median anti-spike SARS-CoV-2 IgG responses 28 days after the boost dose were similar across the three age cohorts (standard-dose groups: 18-55 years, 20 713 arbitrary units [AU]/mL [IQR 13 898-33 550], n=39; 56-69 years, 16 170 AU/mL [10 233-40 353], n=26; and ≥70 years 17 561 AU/mL [9705-37 796], n=47; p=0·68). Neutralising antibody titres after a boost dose were similar across all age groups (median MNA80 at day 42 in the standard-dose groups: 18-55 years, 193 [IQR 113-238], n=39; 56-69 years, 144 [119-347], n=20; and ≥70 years, 161 [73-323], n=47; p=0·40). By 14 days after the boost dose, 208 (>99%) of 209 boosted participants had neutralising antibody responses. T-cell responses peaked at day 14 after a single standard dose of ChAdOx1 nCoV-19 (18-55 years: median 1187 spot-forming cells [SFCs] per million peripheral blood mononuclear cells [IQR 841-2428], n=24; 56-69 years: 797 SFCs [383-1817], n=29; and ≥70 years: 977 SFCs [458-1914], n=48). INTERPRETATION: ChAdOx1 nCoV-19 appears to be better tolerated in older adults than in younger adults and has similar immunogenicity across all age groups after a boost dose. Further assessment of the efficacy of this vaccine is warranted in all age groups and individuals with comorbidities. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midlands NIHR Clinical Research Network, and AstraZeneca.
Published: 2020

16. Gene expression profiling reveals insights into infant immunological and febrile responses to group B meningococcal vaccine

Author: Samuel Channon-Wells, Marta Valente Pinto, Michael Levin, Christina Dold, Harri Hughes, Matthew D. Snape, Christine S. Rollier, Dylan Sheerin, Andrew J. Pollard, Emma Plested, Lisa Stockdale, Hannah Robinson, Adriana Tomic, Ruth E Drury, Daniel H. O'Connor, Manish Sadarangani, Simon Kerridge, and Ushma Galal
Subjects: Male, Medicine (General), Proteome, medicine.disease_cause, IMMUNOGENICITY, 0601 Biochemistry and Cell Biology, Transcriptome, Pneumococcal Vaccines, transcriptomics, Mice, 0302 clinical medicine, Biology (General), Haemophilus Vaccines, 0303 health sciences, LIGHT-CHAIN, IMMUNE-RESPONSES, Applied Mathematics, Neisseria meningitidis, Immunogenicity, SEROGROUP-B, Incidence, Vaccination, systems biology, Articles, vaccines, OPEN-LABEL, Microbiology, Virology & Host Pathogen Interaction, 3. Good health, Computational Theory and Mathematics, INFLUENZA, Host-Pathogen Interactions, Female, General Agricultural and Biological Sciences, Meningitis, Life Sciences & Biomedicine, Information Systems, Biochemistry & Molecular Biology, RNA-SEQ EXPERIMENTS, ANTIBODY-RESPONSES, Fever, QH301-705.5, Bioinformatics, Immunology, 0699 Other Biological Sciences, Meningococcal Vaccines, Meningococcal vaccine, Biology, Article, General Biochemistry, Genetics and Molecular Biology, paediatrics, 03 medical and health sciences, R5-920, proteomics, medicine, Animals, Humans, Diphtheria-Tetanus-Pertussis Vaccine, 030304 developmental biology, 4CMENB VACCINE, Reactogenicity, Science & Technology, Vaccines, Conjugate, General Immunology and Microbiology, Gene Expression Profiling, Immunity, Infant, medicine.disease, Microarray Analysis, PEPTIDOGLYCAN, Gene expression profiling, Meningococcal Infections, Mice, Inbred C57BL, Poliovirus Vaccine, Inactivated, 030217 neurology & neurosurgery, Blood Chemical Analysis
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., A randomised clinical trial evaluates transcriptomic and proteomic profiles following infant concomitant 4CMenB vaccination, compared with control vaccines alone. A novel framework is provided for both understanding and predicting vaccine immunogenicity and reactogenicity.
Published: 2020

17. Peptide-specific recognition of human cytomegalovirus strains controls adaptive natural killer cells

Author: Immo Prinz, Chiara Romagnani, Gilles Gasparoni, Marina Babić, Frederik Heinrich, André Haubner, Adriana Tomic, Mikalai Nienen, Quirin Hammer, Igor Wolfgang Blau, Martin Messerle, Kevin Thurley, Gabriella Pietra, Renate Arnold, Christian Koenecke, Mir-Farzin Mashreghi, Jörn Walter, Pawel Durek, Il-Kang Na, Eva Maria Borst, Timo Rückert, P.G. Hemmati, Josefine Dunst, Jörg Hofmann, and Nina Babel
Subjects: 0301 basic medicine, Human cytomegalovirus, viruses, Cell, Population, Immunology, Cytomegalovirus, Peptide, Biology, 03 medical and health sciences, Viral Proteins, 0302 clinical medicine, medicine, Immunology and Allergy, Humans, education, Receptor, Activating receptors, chemistry.chemical_classification, education.field_of_study, Ligand (biochemistry), medicine.disease, Cell biology, Killer Cells, Natural, 030104 developmental biology, medicine.anatomical_structure, chemistry, T cell subset, Cytomegalovirus Infections, NK Cell Lectin-Like Receptor Subfamily C, 030215 immunology
Abstract: Natural killer (NK) cells are innate lymphocytes that lack antigen-specific rearranged receptors, a hallmark of adaptive lymphocytes. In some people infected with human cytomegalovirus (HCMV), an NK cell subset expressing the activating receptor NKG2C undergoes clonal-like expansion that partially resembles anti-viral adaptive responses. However, the viral ligand that drives the activation and differentiation of adaptive NKG2C+ NK cells has remained unclear. Here we found that adaptive NKG2C+ NK cells differentially recognized distinct HCMV strains encoding variable UL40 peptides that, in combination with pro-inflammatory signals, controlled the population expansion and differentiation of adaptive NKG2C+ NK cells. Thus, we propose that polymorphic HCMV peptides contribute to shaping of the heterogeneity of adaptive NKG2C+ NK cell populations among HCMV-seropositive people.
Published: 2020

18. SIMON, an automated machine learning system reveals immune signatures of influenza vaccine responses

Author: Ivan Tomic, Adriana Tomic, Mark M. Davis, Yael Rosenberg-Hasson, Cornelia L. Dekker, and Holden T. Maecker
Subjects: Adult, CD4-Positive T-Lymphocytes, Male, Speedup, Adolescent, Influenza vaccine, Computer science, Immunology, Datasets as Topic, CD8-Positive T-Lymphocytes, Machine learning, computer.software_genre, Statistical power, Machine Learning, Seasonal influenza, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Immune system, Antigen, T-Lymphocyte Subsets, Influenza, Human, Data Mining, Humans, Immunology and Allergy, Child, 030304 developmental biology, 0303 health sciences, Modalities, Systems Immunology, business.industry, Vaccination, Missing data, 3. Good health, Influenza Vaccines, 030220 oncology & carcinogenesis, Female, Artificial intelligence, business, computer, Algorithms, Difficulty coping, 030215 immunology
Abstract: Machine learning holds considerable promise for understanding complex biological processes such as vaccine responses. Capturing interindividual variability is essential to increase the statistical power necessary for building more accurate predictive models. However, available approaches have difficulty coping with incomplete datasets which is often the case when combining studies. Additionally, there are hundreds of algorithms available and no simple way to find the optimal one. Here, we developed Sequential Iterative Modelling “OverNight” or SIMON, an automated machine learning system that compares results from 128 different algorithms and is particularly suitable for datasets containing many missing values. We applied SIMON to data from five clinical studies of seasonal influenza vaccination. The results reveal previously unrecognized CD4+ and CD8+ T cell subsets strongly associated with a robust antibody response to influenza antigens. These results demonstrate that SIMON can greatly speed up the choice of analysis modalities. Hence, it is a highly useful approach for data-driven hypothesis generation from disparate clinical datasets. Our strategy could be used to gain biological insight from ever-expanding heterogeneous datasets that are publicly available.
Published: 2019

19. The FluPRINT dataset, a multidimensional analysis of the influenza vaccine imprint on the immune system

Author: Ivan Tomic, Holden T. Maecker, Adriana Tomic, Mark M. Davis, and Cornelia L. Dekker
Subjects: Male, Data Descriptor, Live attenuated vaccines, Transcriptome, Machine Learning, Immunogenicity, Vaccine, 0302 clinical medicine, Child, lcsh:Science, Aged, 80 and over, Multidimensional analysis, Vaccines, 0303 health sciences, Immunogenicity, Middle Aged, 3. Good health, Computer Science Applications, Influenza Vaccines, Child, Preschool, Cytokines, Identification (biology), Female, Statistics, Probability and Uncertainty, Information Systems, Adult, Statistics and Probability, Adolescent, Influenza vaccine, Computational biology, Library and Information Sciences, Biology, Immunophenotyping, Education, Young Adult, 03 medical and health sciences, Immune system, Immunity, Humans, Aged, 030304 developmental biology, Inactivated vaccines, Infant, Small sample, Hemagglutination Inhibition Tests, Research data, Serum cytokine, Antibody response, Immune System, Antibody Formation, lcsh:Q, Influenza virus, 030217 neurology & neurosurgery
Abstract: Machine learning has the potential to identify novel biological factors underlying successful antibody responses to influenza vaccines. The first attempts have revealed a high level of complexity in establishing influenza immunity, and many different cellular and molecular components are involved. Of note is that the previously identified correlates of protection fail to account for the majority of individual responses across different age groups and influenza seasons. Challenges remain from the small sample sizes in most studies and from often limited data sets, such as transcriptomic data. Here we report the creation of a unified database, FluPRINT, to enable large-scale studies exploring the cellular and molecular underpinnings of successful antibody responses to influenza vaccines. Over 3,000 parameters were considered, including serological responses to influenza strains, serum cytokines, cell phenotypes, and cytokine stimulations. FluPRINT, facilitates the application of machine learning algorithms for data mining. The data are publicly available and represent a resource to uncover new markers and mechanisms that are important for influenza vaccine immunogenicity., Measurement(s)immune response traitTechnology Type(s)digital curationFactor Type(s)gender • race • visit_age • bmi • flu_vaccination_history • statin_use • influenza_infection_history • influenza_hospitalization • cmv_status • ebv_statusSample Characteristic - OrganismHomo sapiens Machine-accessible metadata file describing the reported data: 10.6084/m9.figshare.9902447
Published: 2019
Full Text: View/download PDF

20. Activation of Innate and Adaptive Immunity by a Recombinant Human Cytomegalovirus Strain Expressing an NKG2D Ligand

Author: Suzana Malić, Stipan Jonjić, Martin Messerle, Mijo Golemac, Eva Mischak-Weissinger, Peggy Riese, Pavankumar Reddy Varanasi, Carlos A. Guzmán, Astrid Krmpotić, Eva Maria Borst, Adriana Tomic, and Hel,holtz Centre for infection research, Inhoffenstr. 7, 38124 Braunschweig, Germany.
Subjects: 0301 basic medicine, Physiology, viruses, Cytomegalovirus, NK cells, Adaptive Immunity, Pathology and Laboratory Medicine, Ligands, Biochemistry, White Blood Cells, Cytomegalovirus Vaccines, Mice, 0302 clinical medicine, Animal Cells, Immune Physiology, Medicine and Health Sciences, Cytotoxic T cell, Public and Occupational Health, Biology (General), Staining, Vaccines, Attenuated vaccine, Immune System Proteins, T Cells, Cell Staining, Animal Models, Acquired immune system, Flow Cytometry, Vaccination and Immunization, Immunohistochemistry, 3. Good health, Killer Cells, Natural, Medical Microbiology, Viral Pathogens, Viruses, Cytomegalovirus Infections, Human Cytomegalovirus, Intercellular Signaling Peptides and Proteins, Cellular Types, Pathogens, HCMV, ULBP2, NKG2D, medicine.drug, Research Article, Herpesviruses, QH301-705.5, Immune Cells, Immunology, chemical and pharmacologic phenomena, Cytotoxic T cells, Mouse Models, Enzyme-Linked Immunosorbent Assay, Biology, Research and Analysis Methods, GPI-Linked Proteins, Real-Time Polymerase Chain Reaction, Vaccines, Attenuated, Microbiology, Antibodies, 03 medical and health sciences, Immune system, Model Organisms, Virology, MHC class I, Genetics, medicine, Animals, Humans, Molecular Biology, Microbial Pathogens, Blood Cells, Organisms, Biology and Life Sciences, Proteins, Cell Biology, RC581-607, biochemical phenomena, metabolism, and nutrition, Immunity, Innate, Disease Models, Animal, 030104 developmental biology, Specimen Preparation and Treatment, biology.protein, Parasitology, Preventive Medicine, Immunologic diseases. Allergy, Cytomegalovirus vaccine, DNA viruses, 030215 immunology
Abstract: Development of an effective vaccine against human cytomegalovirus (HCMV) is a need of utmost medical importance. Generally, it is believed that a live attenuated vaccine would best provide protective immunity against this tenacious pathogen. Here, we propose a strategy for an HCMV vaccine that aims at the simultaneous activation of innate and adaptive immune responses. An HCMV strain expressing the host ligand ULBP2 for the NKG2D receptor was found to be susceptible to control by natural killer (NK) cells, and preserved the ability to stimulate HCMV-specific T cells. Infection with the ULBP2-expressing HCMV strain caused diminished cell surface levels of MHC class I molecules. While expression of the NKG2D ligand increased the cytolytic activity of NK cells, NKG2D engagement in CD8+ T cells provided co-stimulation and compensated for lower MHC class I expression. Altogether, our data indicate that triggering of both arms of the immune system is a promising approach applicable to the generation of a live attenuated HCMV vaccine., Author Summary Human cytomegalovirus (CMV) is a major cause of morbidity and mortality in congenitally infected newborns and immunocompromised individuals, indicating an utmost need for a vaccine to protect these vulnerable groups. Recent experimental studies in animal models, including non-human primates, have shown that attenuated CMVs trigger a potent immune response and are attractive vaccine candidates. However, an effective CMV vaccine is still not available. Here, we demonstrate that rational engineering of a live attenuated human CMV vaccine candidate is feasible. We equipped a CMV strain with an immunostimulatory molecule that is a ligand for an activating receptor present on both Natural Killer cells and CD8+ T cells. Moreover, we deleted several immunoevasins involved in downregulation of MHC class I molecules and of a ligand for Natural Killer cells in order to elicit stronger immune responses. In vitro assays using human immune cells and a first assessment in a humanized mouse model in vivo suggest that the generated CMV strain is attenuated and has the ability to induce a virus-specific immune response. Our study proposes this novel approach for the development of a rationally engineered CMV vaccine.
Published: 2016

21. Inflammatory monocytes and NK cells play a crucial role in DNAM-1-dependent control of cytomegalovirus infection

Author: Stipan Jonjić, Adriana Tomic, Marina Babić, Ilija Brizić, Ulrich H. Koszinowski, Astrid Krmpotić, Ofer Mandelboim, Martin Messerle, Noa S. Kaynan, Stefan Jordan, Vanda Juranić Lisnić, Marco Colonna, Paola Kucan Brlic, Daria Kveštak, Tihana Lenac Rovis, and Pinchas Tsukerman
Subjects: Antigens, Differentiation, T-Lymphocyte, 0301 basic medicine, DOWN-REGULATION, CD96, DNAM-1 CD226, Immunology, Nitric Oxide Synthase Type II, MACROPHAGE ACTIVATION, CCL2, DENDRITIC CELLS, Article, Monocytes, Proinflammatory cytokine, Mice, 03 medical and health sciences, NATURAL-KILLER-CELLS, TIGIT, MCMV, evasion, immune control, DNAM-1, PVR, NK cell, monocyte, Animals, Immunology and Allergy, CD155, Receptor, Research Articles, GENE-EXPRESSION, Mice, Inbred BALB C, MURINE CYTOMEGALOVIRUS, biology, BIOMEDICINE AND HEALTHCARE. Basic Medical Sciences, virus diseases, dNaM, Interleukin-12, eye diseases, 3. Good health, Cell biology, Killer Cells, Natural, Mice, Inbred C57BL, 030104 developmental biology, Cytomegalovirus Infections, biology.protein, Receptors, Virus, VIRUS, sense organs, BIOMEDICINA I ZDRAVSTVO. Temeljne medicinske znanosti, Poliovirus Receptor, RESPONSES
Abstract: Jonjic et al. show that inflammatory macrophages play an essential role in the control of murine CMV (MCMV) infection through a DNAM-1–PVR pathway., The poliovirus receptor (PVR) is a ubiquitously expressed glycoprotein involved in cellular adhesion and immune response. It engages the activating receptor DNAX accessory molecule (DNAM)-1, the inhibitory receptor TIGIT, and the CD96 receptor with both activating and inhibitory functions. Human cytomegalovirus (HCMV) down-regulates PVR expression, but the significance of this viral function in vivo remains unknown. Here, we demonstrate that mouse CMV (MCMV) also down-regulates the surface PVR. The m20.1 protein of MCMV retains PVR in the endoplasmic reticulum and promotes its degradation. A MCMV mutant lacking the PVR inhibitor was attenuated in normal mice but not in mice lacking DNAM-1. This attenuation was partially reversed by NK cell depletion, whereas the simultaneous depletion of mononuclear phagocytes abolished the virus control. This effect was associated with the increased expression of DNAM-1, whereas TIGIT and CD96 were absent on these cells. An increased level of proinflammatory cytokines in sera of mice infected with the virus lacking the m20.1 and an increased production of iNOS by inflammatory monocytes was observed. Blocking of CCL2 or the inhibition of iNOS significantly increased titer of the virus lacking m20.1. In this study, we have demonstrated that inflammatory monocytes, together with NK cells, are essential in the early control of CMV through the DNAM-1–PVR pathway.
Published: 2016

22. Viral regulation of PVR reveals robust capacity of DNAM-1 in cytomegalovirus control by NK cells and macrophages

Author: Tihana Lenac Rovis, Paola Kucan, Noa Stanietsky, Vanda Juranic Lisnic, Ilija Brizic, Stefan Jordan, Adriana Tomic, Marina Babic, Pinchas Tsukerman, Marco Colonna, Martin Messerle, Ofer Mandelboim, Astrid Krmpotic, Stipan Jonjic
Subjects: PVR, DNAM-1, MCMV
Abstract: The poliovirus receptor (PVR, CD155) is a highly conserved and ubiquitously expressed glycoprotein that plays a role in the immune response to tumors and viruses, acting as stress induced ligand. It engages the activating receptor DNAM-1, expressed on the majority of immune cells, the inhibitory receptor TIGIT and CD96, receptor for which both activating and inhibitory functions have been described. We have demonstrated that mouse cytomegalovirus (MCMV) downmodulates surface expression of PVR and characterized the viral protein involved, named m20.1. Since PVR can ligate both inhibitory and activating immune receptors, the consequence of this viral downregulation in vivo was hardly predictable. We showed that MCMV mutant lacking PVR inhibitor was attenuated in normal mice but not in DNAM-1-/- mice, suggesting the dominance of DNAM-1 over other PVR receptors. The attenuation of Δm20.1 MCMV was only partially reversed by NK cell depletion, whereas depletion of macrophages abolished this phenotype. A strong effect of macrophages was associated with their dominant expression of DNAM-1 upon in vivo infection, while TIGIT and CD96 were absent on these cells. We also observed increased production of iNOS in macrophages of mice infected with Δm20.1 virus, as well as increased level of proinflammatory cytokines in sera of those mice, suggesting macrophage polarization towards the inflammation. Altogether, our data show that the deletion of viral inhibitor of PVR augments virus control by NK cells and macrophages via engagement of DNAM-1.
Published: 2015

23. Superior induction and maintenance of protective CD8 T cells in mice infected with mouse cytomegalovirus vector expressing RAE-1γ

Author: Maja Abram, Wiebke Jäger, Adriana Tomic, Stipan Jonjić, Martin Messerle, Bojan Polić, Maja Arapović, Niels A. W. Lemmermann, Felix M. Wensveen, Annette Oxenius, Andreas Busche, Mijo Golemac, Melanie M. Brinkmann, Astrid Krmpotić, Tihana Tršan, Marina Babić, and Research group viral immune modulation, Helmholtz Centre for infection research, Braunschweig, Germany
Subjects: Genetic Vectors, Retinoic acid, Cytomegalovirus, chemical and pharmacologic phenomena, Biology, CD8-Positive T-Lymphocytes, Epitope, Statistics, Nonparametric, 03 medical and health sciences, chemistry.chemical_compound, Mice, 0302 clinical medicine, Immune system, In vivo, Cytotoxic T cell, Animals, Vector (molecular biology), 030304 developmental biology, Immune Evasion, Mice, Knockout, 0303 health sciences, Mice, Inbred BALB C, Vaccines, Synthetic, Multidisciplinary, BIOMEDICINE AND HEALTHCARE. Basic Medical Sciences, Membrane Proteins, Biological Sciences, NKG2D, Flow Cytometry, Virology, Listeria monocytogenes, 3. Good health, CD8 T cell vaccine, RAE-1 gamma, vaccine vector, Mice, Inbred C57BL, chemistry, NK Cell Lectin-Like Receptor Subfamily K, BIOMEDICINA I ZDRAVSTVO. Temeljne medicinske znanosti, CD8, 030215 immunology
Abstract: Due to a unique pattern of CD8 T-cell response induced by cytomegaloviruses (CMVs), live attenuated CMVs are attractive candidates for vaccine vectors for a number of clinically relevant infections and tumors. NKG2D is one of the most important activating NK cell receptors that plays a role in costimulation of CD8 T cells. Here we demonstrate that the expression of CD8 T-cell epitope of Listeria monocytogenes by a recombinant mouse CMV (MCMV) expressing the NKG2D ligand retinoic acid early-inducible protein 1-gamma (RAE-1γ) dramatically enhanced the effectiveness and longevity of epitope-specific CD8 T-cell response and conferred protection against a subsequent challenge infection with Listeria monocytogenes. Unexpectedly, the attenuated growth in vivo of the CMV vector expressing RAE-1γ and its capacity to enhance specific CD8 T-cell response were preserved even in mice lacking NKG2D, implying additional immune function for RAE-1γ beyond engagement of NKG2D. Thus, vectors expressing RAE-1γ represent a promising approach in the development of CD8 T-cell-based vaccines.
Published: 2013

24. Complex viral regulation of PVR by MCMV to avoid NK cell recognition

Author: Tihana Lenac Rovis, Noa Stanietsky, Stefan Jordan, Vanda Juranic Lisnic, Adriana Tomic, Marina Babic, Astrid Krmpotic, Pinhas Tsukerman, Ofer Mandelboim, Stipan Jonjic
Subjects: viruses, virus diseases, eye diseases, pvr virus cytomegalovirus downregulation MCMV
Abstract: Human cytomegalovirus (HCMV) is ubiquitous beta-herpesvirus that infects the majority of human populations. Murine cytomegalovirus (MCMV) is most widely used model for HCMV pathogenesis since the two viruses are genetically related and share many biological and pathological features. Both viruses cause persistent infection that lasts for life thanks to a plethora of viral immunoevasion genes targeted at both innate and adaptive arms of the immune system. Among many other immunoreceptor ligands targeted by HCMV is CD155 (PVR). PVR serves as a ligand for three NK and T cell receptors: activating receptors CD226 (DNAM-1) and CD96 (TACTILE) and inhibitory receptor TIGIT. Previously it was shown that HCMV blocks the surface expression of PVR. Here we show negative regulation of PVR by MCMV and attempt to dissect the mechanisms behind the regulation. Infection by MCMV causes increased transcription of the PVR gene however infected cells show diminished amounts of surface PVR. Using multiple viral deletion mutants we show that MCMV has dedicated two viral genes towards regulation of PVR surface expression: m154 and m20. Deletion of either m154 or m20 MCMV ORFs prevented downregulation and resulted in viral attenuation in vivo, while deletion of both ORFs resulted in upregulation of PVR on the cell surface. While m20 regulates the maturation of PVR, mechanism of action of m154 is still unknown. m20 gene region displays a very complex transcriptional profile with multiple overlapping 3’ co-terminal transcripts that show distinct temporal expression. Recent work on ribosomal footprinting in HCMV showed that such complex transcriptional profiles are more widespread among cytomegaloviruses than previously thought. In our transcriptomic study, we have identified several loci in MCMV genome that display similar expression profile. Overlapping 3’ co-terminal transcripts have the potential to encode different proteins either by using different ORFs or by producing N-terminal truncations. Using a panel of deletion mutants we have managed to identify transcript responsible for PVR regulation via ER retention.
Published: 2013

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources

Refine your results

24 results on '"Adriana Tomic"'

1. Omicron infection following vaccination enhances a broad spectrum of immune responses dependent on infection history

2. CD4+ and CD8+ T cells and antibodies are associated with protection against Delta vaccine breakthrough infection: a nested case-control study within the PITCH study

3. Divergent trajectories of antiviral memory after SARS-CoV-2 infection

4. SIMON: Open-Source Knowledge Discovery Platform

5. Gene expression profiling reveals insights into infant immunological and febrile responses to group B meningococcal vaccine

6. Systems Immunology: Revealing Influenza Immunological Imprint

7. Cytomegalovirus m154 hinders CD48 cell-surface expression and promotes viral escape from host natural killer cell control.

8. Omicron BA.1/BA.2 infections in triple-vaccinated individuals enhance a diverse repertoire of mucosal and blood immune responses

9. Constructing custom-made radiotranscriptomic signatures of vascular inflammation from routine CT angiograms: a prospective outcomes validation study in COVID-19

10. Divergent trajectories of antiviral memory after SARS-CoV-2 infection

11. Divergent trajectories of antiviral memory after SARS-Cov-2 infection

12. MCMV based vaccine vectors expressing full-length viral proteins provide long-term humoral immune protection upon a single-shot vaccination

13. A blood atlas of COVID-19 defines hallmarks of disease severity and specificity

14. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

15. Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2/3 trial

16. Gene expression profiling reveals insights into infant immunological and febrile responses to group B meningococcal vaccine

17. Peptide-specific recognition of human cytomegalovirus strains controls adaptive natural killer cells

18. SIMON, an automated machine learning system reveals immune signatures of influenza vaccine responses

19. The FluPRINT dataset, a multidimensional analysis of the influenza vaccine imprint on the immune system

20. Activation of Innate and Adaptive Immunity by a Recombinant Human Cytomegalovirus Strain Expressing an NKG2D Ligand

21. Inflammatory monocytes and NK cells play a crucial role in DNAM-1-dependent control of cytomegalovirus infection

22. Viral regulation of PVR reveals robust capacity of DNAM-1 in cytomegalovirus control by NK cells and macrophages

23. Superior induction and maintenance of protective CD8 T cells in mice infected with mouse cytomegalovirus vector expressing RAE-1γ

24. Complex viral regulation of PVR by MCMV to avoid NK cell recognition

Catalog

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Publication Type

Journal

Database

Publisher

24 results on '"Adriana Tomic"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources