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1. Community seroprevalence of SARS-CoV-2 in children and adolescents in England, 2019–2021

Author

Ratcliffe, Helen, primary, Tiley, K S, additional, Andrews, Nick, additional, Amirthalingam, Gayatri, additional, Vichos, I, additional, Morey, E, additional, Douglas, N L, additional, Marinou, S, additional, Plested, Emma, additional, Aley, Parvinder, additional, Galiza, Eva P, additional, Faust, Saul N, additional, Hughes, S, additional, Murray, Clare S, additional, Roderick, Marion, additional, Shackley, Fiona, additional, Oddie, Sam J, additional, Lees, Tim, additional, Turner, D P J, additional, Raman, M, additional, Owens, Stephen, additional, Turner, Paul, additional, Cockerill, H, additional, Lopez Bernal, J, additional, Linley, E, additional, Borrow, Ray, additional, Brown, Kevin, additional, Ramsay, Mary Elizabeth, additional, Voysey, M, additional, and Snape, Matthew D, additional

Published
2022
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2. Divergent trajectories of antiviral memory after SARS-CoV-2 infection

Author

Tomic, A, Skelly, DT, Ogbe, A, O’Connor, D, Pace, M, Adland, E, Alexander, F, Ali, M, Allott, K, Azim Ansari, M, Belij-Rammerstorfer, S, Bibi, S, Blackwell, L, Brown, A, Brown, H, Cavell, B, Clutterbuck, EA, de Silva, T, Eyre, D, Lumley, S, Flaxman, A, Grist, J, Hackstein, C-P, Halkerston, R, Harding, AC, Hill, J, James, T, Jay, C, Johnson, SA, Kronsteiner, B, Lie, Y, Linder, A, Longet, S, Marinou, S, Matthews, PC, Mellors, J, Petropoulos, C, Rongkard, P, Sedik, C, Silva-Reyes, L, Smith, H, Stockdale, L, Taylor, S, Thomas, S, Tipoe, T, Turtle, L, Vieira, VA, Wrin, T, Stafford, L, Abuelgasim, H, Alhussni, A, Arancibia-Cárcamo, CV, Borak, M, Cutteridge, J, Deeks, A, Denly, L, Dimitriadis, S, Fassih, S, Foord, T, Fordwoh, T, Holmes, J, Horsington, B, Kerneis, S, Kim, D, Lillie, K, Morrow, J, O’Donnell, D, Ritter, TG, Simmons, B, Taylor, A, Thomas, SR, Warren, Y, Watson, AJR, Weeks, E, Wilson, R, Young, R, Duncan, CJA, Moore, SC, Payne, R, Richter, A, Rowland-Jones, S, Mentzer, AJ, Cassar, MP, Dong, T, Fries, A, Gilbert-Jaramillo, J, Ho, L-P, Knight, JC, Neubauer, S, Peng, Y, Petousi, N, Raman, B, Talbot, NP, Pollard, AJ, Lambe, T, Conlon, CP, Jeffery, K, Travis, S, Goulder, P, Frater, J, Carroll, MW, James, WS, Klenerman, P, Barnes, E, Dold, C, and Dunachie, SJ

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

3. Community seroprevalence of SARS-CoV-2 in children and adolescents in England, 2019-2021.

Author

Ratcliffe, Helen, Tiley, K. S., Andrews, Nick, Amirthalingam, Gayatri, Vichos, I., Morey, E., Douglas, N. L., Marinou, S., Plested, Emma, Aley, Parvinder, Galiza, Eva P., Faust, Saul N., Hughes, S., Murray, Clare S., Roderick, Marion, Shackley, Fiona, Oddie, Sam J., Lees, Tim, Turner, D. P. J., and Raman, M.

Subjects
COMMUNITIES, SEROPREVALENCE, MEDICAL personnel, ADOLESCENCE, PUBLIC health personnel, COVID-19 pandemic
Published
2023
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4. Two doses of SARS-CoV-2 vaccination induce robust immune responses to emerging SARS-CoV-2 variants of concern

Author

Skelly, DT, Harding, AC, Gilbert-Jaramillo, J, Knight, ML, Longet, S, Brown, A, Adele, S, Adland, E, Brown, H, Chinnakannan, S, Donnison, T, Ali, M, Rongkard, P, Pace, M, Zacharopoulou, P, Robinson, N, Csala, A, De Lara, C, Hutchings, CL, Mehta, H, Lee, LN, Edmans, M, Hackstein, C-P, Phalora, P, Li, W, Phillips, E, Malone, T, Ogbe, A, Jay, C, Tipoe, T, Tipton, T, Stafford, L, Mentzer, AJ, Johnson, SA, Amini, A, Marjot, T, Dimitriadis, S, Simmons, B, Deeks, A, Kerneis, S, Abuelgasim, H, Wilson, R, Thomas, SR, Watson, A, Alhussni, A, Cutteridge, J, Weeks, E, Denly, L, Lillie, K, Holmes, J, Matthews, PC, O’Donnell, D, Tan, TK, Schimanski, L, Huang, K-YA, Rijal, P, Turtle, L, de Silva, T, Richter, A, Duncan, CJA, Payne, RP, Moore, SC, Knight, JC, Cassar, MP, Raman, B, Neubauer, S, Fries, A, Talbot, NP, Petousi, N, Ho, L-P, Peng, Y, Dong, T, Camara, S, Marinou, S, Linder, A, Adlou, S, Kasanyinga, M, Bridges-Webb, A, Hill, J, Silva-Reyes, L, Blackwell, L, Frater, J, Goulder, P, Conlon, CP, Jeffery, K, Dold, C, Pollard, AJ, Sigal, A, de Oliveira, T, Townsend, AR, Klenerman, P, Dunachie, SJ, Barnes, E, Carroll, MW, and James, WS

Abstract

The extent to which immune responses to natural infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and immunization with vaccines protect against variants of concern (VOC) is of increasing importance. Accordingly, here we analyse antibodies and T cells of a recently vaccinated, UK cohort, alongside those recovering from natural infection in early 2020. We show that neutralization of the VOC compared to a reference isolate of the original circulating lineage, B, is reduced: more profoundly against B.1.351 than for B.1.1.7, and in responses to infection or a single dose of vaccine than to a second dose of vaccine. Importantly, high magnitude T cell responses are generated after two vaccine doses, with the majority of the T cell response directed against epitopes that are conserved between the prototype isolate B and the VOC. Vaccination is required to generate high potency immune responses to protect against these and other emergent variants.

Published
2021

5. Correlates of protection against symptomatic and asymptomatic SARS-CoV-2 infection

Author

Feng, S, Phillips, DJ, White, T, Sayal, H, Aley, PK, Bibi, S, Dold, C, Fuskova, M, Gilbert, SC, Hirsch, I, Humphries, HE, Jepson, B, Kelly, EJ, Plested, E, Shoemaker, K, Thomas, KM, Vekemans, J, Villafana, TL, Lambe, T, Pollard, AJ, Voysey, M, Adlou, S, Allen, L, Angus, B, Anslow, R, Asselin, M-C, Baker, N, Baker, P, Barlow, T, Beveridge, A, Bewley, KR, Brown, P, Brunt, E, Buttigieg, KR, Camara, S, Charlton, S, Chiplin, E, Cicconi, P, Clutterbuck, EA, Collins, AM, Coombes, NS, Clemens, SAC, Davison, M, Demissie, T, Dinesh, T, Douglas, AD, Duncan, CJA, Emary, KRW, Ewer, KJ, Felle, S, Ferreira, DM, Finn, A, Folegatti, PM, Fothergill, R, Fraser, S, Garlant, H, Gatcombe, L, Godwin, KJ, Goodman, AL, Green, CA, Hallis, B, Hart, TC, Heath, PT, Hill, H, Hill, AVS, Jenkin, D, Kasanyinga, M, Kerridge, S, Knight, C, Leung, S, Libri, V, Lillie, PJ, Marinou, S, McGlashan, J, McGregor, AC, McInroy, L, Minassian, AM, Mujadidi, YF, Penn, EJ, Petropoulos, CJ, Pollock, KM, Proud, PC, Provstgaard-Morys, S, Rajapaska, D, Ramasamy, MN, Sanders, K, Shaik, I, Singh, N, Smith, A, Snape, MD, Song, R, Shrestha, S, Sutherland, RK, Thomson, EC, Turner, DPJ, Webb-Bridges, A, Wrin, T, Williams, CJ, and Group, Oxford COVID Vaccine Trial

Subjects
Male, Antibodies, Viral, Neutralization, Cohort Studies, Multiplex, Asymptomatic Infections, 11 Medical and Health Sciences, Aged, 80 and over, Vaccines, biology, medicine.diagnostic_test, Vaccination, General Medicine, Middle Aged, Titer, Treatment Outcome, Infectious diseases, Female, Antibody, medicine.symptom, Adult, medicine.medical_specialty, COVID-19 Vaccines, Coronavirus disease 2019 (COVID-19), Adolescent, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Immunology, Immunization, Secondary, Asymptomatic, General Biochemistry, Genetics and Molecular Biology, World health, Article, Young Adult, Immune system, Statistical significance, Internal medicine, medicine, Humans, Aged, Infection Control, business.industry, SARS-CoV-2, Patient Acuity, COVID-19, Vaccine efficacy, Antibodies, Neutralizing, United Kingdom, Immunity, Humoral, Immunoassay, biology.protein, business
Abstract

The global supply of COVID-19 vaccines remains limited. An understanding of the immune response that is predictive of protection could facilitate rapid licensure of new vaccines. Data from a randomized efficacy trial of the ChAdOx1 nCoV-19 (AZD1222) vaccine in the United Kingdom was analyzed to determine the antibody levels associated with protection against SARS-CoV-2. Binding and neutralizing antibodies at 28 days after the second dose were measured in infected and noninfected vaccine recipients. Higher levels of all immune markers were correlated with a reduced risk of symptomatic infection. A vaccine efficacy of 80% against symptomatic infection with majority Alpha (B.1.1.7) variant of SARS-CoV-2 was achieved with 264 (95% CI: 108, 806) binding antibody units (BAU)/ml: and 506 (95% CI: 135, not computed (beyond data range) (NC)) BAU/ml for anti-spike and anti-RBD antibodies, and 26 (95% CI: NC, NC) international unit (IU)/ml and 247 (95% CI: 101, NC) normalized neutralization titers (NF50) for pseudovirus and live-virus neutralization, respectively. Immune markers were not correlated with asymptomatic infections at the 5% significance level. These data can be used to bridge to new populations using validated assays, and allow extrapolation of efficacy estimates to new COVID-19 vaccines., Defined levels of SARS-CoV-2-specific binding and neutralizing antibodies elicited by the COVID-19 vaccine ChAdOx1 nCoV-19 are identified as correlates of protection against symptomatic infection.

Published
2021

8. Serum HCoV-spike specific antibodies do not protect against subsequent SARS-CoV-2 infection in children and adolescents.

Author

Ratcliffe H, Tiley KS, Longet S, Tonry C, Roarty C, Watson C, Amirthalingam G, Vichos I, Morey E, Douglas NL, Marinou S, Plested E, Aley PK, Galiza E, Faust SN, Hughes S, Murray C, Roderick MR, Shackley F, Oddie S, Lee TWR, Turner DPJ, Raman M, Owens S, Turner PJ, Cockerill H, Lopez Bernal J, Ijaz S, Poh J, Shute J, Linley E, Borrow R, Hoschler K, Brown KE, Carroll MW, Klenerman P, Dunachie SJ, Ramsay M, Voysey M, Waterfield T, and Snape MD

Abstract

SARS-CoV-2 infections in children are generally asymptomatic or mild and rarely progress to severe disease and hospitalization. Why this is so remains unclear. Here we explore the potential for protection due to pre-existing cross-reactive seasonal coronavirus antibodies and compare the rate of antibody decline for nucleocapsid and spike protein in serum and oral fluid against SARS-CoV-2 within the pediatric population. No differences in seasonal coronaviruses antibody concentrations were found at baseline between cases and controls, suggesting no protective effect from pre-existing immunity against seasonal coronaviruses. Antibodies against seasonal betacoronaviruses were boosted in response to SARS-CoV-2 infection. In serum, anti-nucleocapsid antibodies fell below the threshold of positivity more quickly than anti-spike protein antibodies. These findings add to our understanding of protection against infection with SARS-CoV-2 within the pediatric population, which is important when considering pediatric SARS-CoV-2 immunization policies., Competing Interests: M.D.S. acted on behalf of the University of Oxford as an investigator on studies funded or sponsored by vaccine manufacturers, including AstraZeneca, GlaxoSmithKline, Pfizer, Novavax, Janssen, Medimmune, and MCM. He received no personal financial payment for this work. Subsequent to this study MDS is employed by Moderna Biotech UK and holds equity in this company. S.N.F. acts on behalf of University Hospital Southampton National Health Service (NHS) Foundation Trust as an investigator or providing consultative advice, or both, on clinical trials and studies of COVID-19 and other vaccines funded or sponsored by vaccine manufacturers including Janssen, Pfizer, AstraZeneca, GlaxoSmithKline, Novavax, Seqirus, Sanofi, Medimmune, Merck, and Valneva. He receives no personal financial payment for this work. M.R. has provided post-marketing surveillance reports on vaccines for Pfizer and GlaxoSmithKline for which a cost recovery charge is made. All other authors declare no competing interests. M.C. and S.L. are funded by US Food and Drug Administration Medical Countermeasures Initiative, contract 75F40120C00085., (© 2023 The Authors.)

Published
2023
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9. Divergent trajectories of antiviral memory after SARS-CoV-2 infection.

Author

Tomic A, Skelly DT, Ogbe A, O'Connor D, Pace M, Adland E, Alexander F, Ali M, Allott K, Azim Ansari M, Belij-Rammerstorfer S, Bibi S, Blackwell L, Brown A, Brown H, Cavell B, Clutterbuck EA, de Silva T, Eyre D, Lumley S, Flaxman A, Grist J, Hackstein CP, Halkerston R, Harding AC, Hill J, James T, Jay C, Johnson SA, Kronsteiner B, Lie Y, Linder A, Longet S, Marinou S, Matthews PC, Mellors J, Petropoulos C, Rongkard P, Sedik C, Silva-Reyes L, Smith H, Stockdale L, Taylor S, Thomas S, Tipoe T, Turtle L, Vieira VA, Wrin T, Pollard AJ, Lambe T, Conlon CP, Jeffery K, Travis S, Goulder P, Frater J, Mentzer AJ, Stafford L, Carroll MW, James WS, Klenerman P, Barnes E, Dold C, and Dunachie SJ

Subjects
Antibodies, Viral, Antiviral Agents, Humans, Longitudinal Studies, Spike Glycoprotein, Coronavirus, COVID-19, SARS-CoV-2
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., (© 2022. The Author(s).)

Published
2022
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