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1. Monkeypox virus-infected individuals mount comparable humoral immune responses as Smallpox-vaccinated individuals

Author

Ashley D. Otter, Scott Jones, Bethany Hicks, Daniel Bailey, Helen Callaby, Catherine Houlihan, Tommy Rampling, Nicola Claire Gordon, Hannah Selman, Panayampalli S. Satheshkumar, Michael Townsend, Ravi Mehta, Marcus Pond, Rachael Jones, Deborah Wright, Clarissa Oeser, Simon Tonge, Ezra Linley, Georgia Hemingway, Tom Coleman, Sebastian Millward, Aaron Lloyd, Inger Damon, Tim Brooks, Richard Vipond, Cathy Rowe, and Bassam Hallis

Subjects
Science
Abstract

Abstract In early 2022, a cluster of monkeypox virus (MPXV) infection (mpox) cases were identified within the UK with no prior travel history to MPXV-endemic regions. Subsequently, case numbers exceeding 80,000 were reported worldwide, primarily affecting gay, bisexual, and other men who have sex with men (GBMSM). Public health agencies worldwide have offered the IMVANEX Smallpox vaccination to these individuals at high-risk to provide protection and limit the spread of MPXV. We have developed a comprehensive array of ELISAs to study poxvirus-induced antibodies, utilising 24 MPXV and 3 Vaccinia virus (VACV) recombinant antigens. Panels of serum samples from individuals with differing Smallpox-vaccine doses and those with prior MPXV infection were tested on these assays, where we observed that one dose of Smallpox vaccination induces a low number of antibodies to a limited number of MPXV antigens but increasing with further vaccination doses. MPXV infection induced similar antibody responses to diverse poxvirus antigens observed in Smallpox-vaccinated individuals. We identify MPXV A27 as a serological marker of MPXV-infection, whilst MPXV M1 (VACV L1) is likely IMVANEX-specific. Here, we demonstrate analogous humoral antigen recognition between both MPXV-infected or Smallpox-vaccinated individuals, with binding to diverse yet core set of poxvirus antigens, providing opportunities for future vaccine (e.g., mRNA) and therapeutic (e.g., mAbs) design.

Published
2023
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2. Effect of second booster vaccinations and prior infection against SARS-CoV-2 in the UK SIREN healthcare worker cohortResearch in context

Author

Peter D. Kirwan, Victoria J. Hall, Sarah Foulkes, Ashley D. Otter, Katie Munro, Dominic Sparkes, Anna Howells, Naomi Platt, Jonathan Broad, David Crossman, Chris Norman, Diane Corrigan, Christopher H. Jackson, Michelle Cole, Colin S. Brown, Ana Atti, Jasmin Islam, Anne M. Presanis, Andre Charlett, Daniela De Angelis, Susan Hopkins, Tracy Lewis, Steve Bain, Rebeccah Thomas, John Geen, Carla Pothecary, Sean Cutler, John Northfield, Cathy Price, Johanne Tomlinson, Sarah Knight, Emily Macnaughton, Ekaterina Watson, Rajeka Lazarus, Aaran Sinclair, Joanne Galliford, Bridgett Masunda, Tabitha Mahungu, Alison Rodger, Esther Hanison, Simon Warren, Swati Jain, Mariyam Mirfenderesky, Natasha Mahabir, Rowan Pritchard-Jones, Diane Wycherley, Claire Gabriel, Elijah Matovu, Philippa Bakker, Simantee Guha, S. Gormley, James Pethick, Georgina Butt, Stacey Pepper, Luke Bedford, Paul Ridley, Jane Democratis, Manjula Meda, Anu Chawla, Fran Westwell, Nagesh Kalakonda, Sheena Khanduri, Allison Doel, Sumita Pai, Christian Hacon, Davis Nwaka, Veronica Mendez Moro, A. Moody, Cressida Auckland, Stephanie Prince, Thushan de Silva, Helen Shulver, A. Shah, C. Jones, Banerjee Subhro-Osuji, Angela Houston, Tim Planche, Martin Booth, Christopher Duff, Jonnie Aeron-Thomas, Ray Chaudhuri, David Hilton, Hannah Jory, Zehra'a Al-Khafaji, Philippa Kemsley, Ruth Longfellow, David Boss, Simon Brake, Louise Coke, Ngozi Elumogo, Scott Latham, Chinari Subudhi, Ina Hoad, Claire Thomas, Nihil Chitalia, Tracy Edmunds, Helen Ashby, John Elliott, Beverley Wilkinson, Abby Rand, Catherine Thompson, K. Agwuh, Anna Grice, Kelly Moran, Vijayendra Waykar, Yvonne Lester, Lauren Sach, Kathryn Court, Nikki White, Clair Favager, Kyra Holliday, Jayne Harwood, Brendan Payne, Karen Burns, Lynda Fothergill, Alejandro Arenas-Pinto, Abigail Severn, Kerryanne Brown, Katherine Gray, Jane Dare, Qi Zheng, Kathryn Hollinshead, Robert Shorten, Alun Roebuck, Christopher Holmes, Martin Wiselka, Barzo Faris, Liane Marsh, Clare McAdam, Lisa Ditchfield, Zaman Qazzafi, G. Boyd, N. Wong, Sarah Brand, Jack Squires, John Ashcroft, Ismaelette Del Rosario, Joanne Howard, Emma Ward, Gemma Harrison, Joely Morgan, Claire Corless, Ruth Penn, Nick Wong, Manny Bagary, Nadezda Starkova, Mandy Beekes, Mandy Carnahan, Shivani Khan, Shekoo Mackay, Keneisha Lewis, Graham Pickard, Joy Dawson, Lauren Finlayson, Euan Cameron, Anne Todd, Sebastien Fagegaltier, Sally Mavin, Alexandra Cochrane, Andrew Gibson, Sam Donaldson, Kate Templeton, Martin Malcolm, Beth Smith, Devesh Dhasmana, Susan Fowler, Antonia Ho, Michael Murphy, Claire Beith, Manish Patel, Elizabeth Boyd, Val Irvine, Alison Grant, Rebecca Temple-Purcell, Clodagh Loughrey, Elinor Hanna, Frances Johnston, Angel Boulos, Fiona Thompson, Yuri Protaschik, Susan Regan, Tracy Donaghy, Maurice O'Kane, Omolola Akinbami, Paola Barbero, Tim Brooks, Meera Chand, Ferdinando Insalata, Palak Joshi, Anne-Marie O'Connell, Mary Ramsay, Ayoub Saei, Maria Zambon, Ezra Linley, Simon Tonge, Enemona Adaji, Omoyeni Adebiyi, Nick Andrews, Joanna Conneely, Paul Conneely, Angela Dunne, Simone Dyer, Hannah Emmett, Nipunadi Hettiarachchi, Nishanthan Kapirial, Jameel Khawam, Edward Monk, Sophie Russell, Andrew Taylor-Kerr, Jean Timeyin, Silvia D'Arcangelo, Cathy Rowe, Amanda Semper, Eileen Gallagher, Robert Kyffin, Lisa Cromey, Desmond Areghan, Jennifer Bishop, Melanie Dembinsky, Laura Dobbie, Josie Evans, David Goldberg, Lynne Haahr, Annelysse Jorgenson, Ayodeji Matuluko, Laura Naismith, Desy Nuryunarsih, Alexander Olaoye, Caitlin Plank, Lesley Price, Nicole Sergenson, Sally Stewart, Andrew Telfer, Jennifer Weir, Ellen De Lacy, Yvette Ellis, Susannah Froude, Guy Stevens, Linda Tyson, Susanna Dunachie, Paul Klenerman, Chris Duncan, Rebecca Payne, Lance Turtle, Alex Richter, Thushan De Silva, Eleanor Barnes, Daniel Wootton, Oliver Galgut, Jonathan Heeney, Helen Baxendale, Javier Castillo-Olivares, Rupert Beale, Edward Carr, Wendy Barclay, Maya Moshe, Massimo Palmarini, Brian Willett, John Kenneth Baillie, Jennie Evans, and Erika Aquino

Subjects
SARS-CoV-2, Vaccine effectiveness, Asymptomatic, Symptomatic, Healthcare worker, Cohort study, Public aspects of medicine, RA1-1270
Abstract

Summary: Background: The protection of fourth dose mRNA vaccination against SARS-CoV-2 is relevant to current global policy decisions regarding ongoing booster roll-out. We aimed to estimate the effect of fourth dose vaccination, prior infection, and duration of PCR positivity in a highly-vaccinated and largely prior-COVID-19 infected cohort of UK healthcare workers. Methods: Participants underwent fortnightly PCR and regular antibody testing for SARS-CoV-2 and completed symptoms questionnaires. A multi-state model was used to estimate vaccine effectiveness (VE) against infection from a fourth dose compared to a waned third dose, with protection from prior infection and duration of PCR positivity jointly estimated. Findings: 1298 infections were detected among 9560 individuals under active follow-up between September 2022 and March 2023. Compared to a waned third dose, fourth dose VE was 13.1% (95% CI 0.9 to 23.8) overall; 24.0% (95% CI 8.5 to 36.8) in the first 2 months post-vaccination, reducing to 10.3% (95% CI −11.4 to 27.8) and 1.7% (95% CI −17.0 to 17.4) at 2–4 and 4–6 months, respectively. Relative to an infection >2 years ago and controlling for vaccination, 63.6% (95% CI 46.9 to 75.0) and 29.1% (95% CI 3.8 to 43.1) greater protection against infection was estimated for an infection within the past 0–6, and 6–12 months, respectively. A fourth dose was associated with greater protection against asymptomatic infection than symptomatic infection, whilst prior infection independently provided more protection against symptomatic infection, particularly if the infection had occurred within the previous 6 months. Duration of PCR positivity was significantly lower for asymptomatic compared to symptomatic infection. Interpretation: Despite rapid waning of protection, vaccine boosters remain an important tool in responding to the dynamic COVID-19 landscape; boosting population immunity in advance of periods of anticipated pressure, such as surging infection rates or emerging variants of concern. Funding: UK Health Security Agency, Medical Research Council, NIHR HPRU Oxford, Bristol, and others.

Published
2024
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3. Ethnic differences in cellular and humoral immune responses to SARS-CoV-2 vaccination in UK healthcare workers: a cross-sectional analysisResearch in context

Author

Christopher A. Martin, Joshua Nazareth, Amar Jarkhi, Daniel Pan, Mrinal Das, Nicola Logan, Sam Scott, Luke Bryant, Neha Abeywickrama, Oluwatobi Adeoye, Aleem Ahmed, Aqua Asif, Srini Bandi, Nisha George, Marjan Gohar, Laura J. Gray, Ross Kaszuba, Jitendra Mangwani, Marianne Martin, Arumugam Moorthy, Valerie Renals, Lucy Teece, Denny Vail, Kamlesh Khunti, Paul Moss, Andrea Tattersall, Bassam Hallis, Ashley D. Otter, Cathy Rowe, Brian J. Willett, Pranab Haldar, Andrea Cooper, and Manish Pareek

Subjects
SARS-CoV-2, COVID-19, Vaccine, Ethnicity, Heathcare worker, Medicine (General), R5-920
Abstract

Summary: Background: Few studies have compared SARS-CoV-2 vaccine immunogenicity by ethnic group. We sought to establish whether cellular and humoral immune responses to SARS-CoV-2 vaccination differ according to ethnicity in UK Healthcare workers (HCWs). Methods: In this cross-sectional analysis, we used baseline data from two immunological cohort studies conducted in HCWs in Leicester, UK. Blood samples were collected between March 3, and September 16, 2021. We excluded HCW who had not received two doses of SARS-CoV-2 vaccine at the time of sampling and those who had serological evidence of previous SARS-CoV-2 infection. Outcome measures were SARS-CoV-2 spike-specific total antibody titre, neutralising antibody titre and ELISpot count. We compared our outcome measures by ethnic group using univariable (t tests and rank-sum tests depending on distribution) and multivariable (linear regression for antibody titres and negative binomial regression for ELISpot counts) tests. Multivariable analyses were adjusted for age, sex, vaccine type, length of interval between vaccine doses and time between vaccine administration and sample collection and expressed as adjusted geometric mean ratios (aGMRs) or adjusted incidence rate ratios (aIRRs). To assess differences in the early immune response to vaccination we also conducted analyses in a subcohort who provided samples between 14 and 50 days after their second dose of vaccine. Findings: The total number of HCWs in each analysis were 401 for anti-spike antibody titres, 345 for neutralising antibody titres and 191 for ELISpot. Overall, 25.4% (19.7% South Asian and 5.7% Black/Mixed/Other) were from ethnic minority groups. In analyses including the whole cohort, neutralising antibody titres were higher in South Asian HCWs than White HCWs (aGMR 1.47, 95% CI [1.06–2.06], P = 0.02) as were T cell responses to SARS-CoV-2 S1 peptides (aIRR 1.75, 95% CI [1.05–2.89], P = 0.03). In a subcohort sampled between 14 and 50 days after second vaccine dose, SARS-CoV-2 spike-specific antibody and neutralising antibody geometric mean titre (GMT) was higher in South Asian HCWs compared to White HCWs (9616 binding antibody units (BAU)/ml, 95% CI [7178–12,852] vs 5888 BAU/ml [5023–6902], P = 0.008 and 2851 95% CI [1811–4487] vs 1199 [984–1462], P

Published
2023
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4. Quantitative, multiplexed, targeted proteomics for ascertaining variant specific SARS-CoV-2 antibody response

Author

Ivan Doykov, Tomas Baldwin, Justyna Spiewak, Kimberly C. Gilmour, Joseph M. Gibbons, Corinna Pade, Catherine J. Reynolds, Áine McKnight, Mahdad Noursadeghi, Mala K. Maini, Charlotte Manisty, Thomas Treibel, Gabriella Captur, Marianna Fontana, Rosemary J. Boyton, Daniel M. Altmann, Tim Brooks, Amanda Semper, James C. Moon, Kevin Mills, Wendy E. Heywood, Hakam Abbass, Aderonke Abiodun, Mashael Alfarih, Zoe Alldis, Oliver E. Amin, Mervyn Andiapen, Jessica Artico, João B. Augusto, Georgina L. Baca, Sasha N.L. Bailey, Anish N. Bhuva, Alex Boulter, Ruth Bowles, Olivia V. Bracken, Ben O’Brien, Natalie Bullock, David K. Butler, Olivia Carr, Nicola Champion, Carmen Chan, Aneesh Chandran, Tom Coleman, Jorge Couto de Sousa, Xose Couto-Parada, Eleanor Cross, Teresa Cutino-Moguel, Silvia D’Arcangelo, Rhodri H. Davies, Brooke Douglas, Cecilia Di Genova, Keenan Dieobi-Anene, Mariana O. Diniz, Anaya Ellis, Karen Feehan, Malcolm Finlay, Nasim Forooghi, Sasha Francis, David Gillespie, Derek Gilroy, Matt Hamblin, Gabrielle Harker, Georgia Hemingway, Jacqueline Hewson, Wendy Heywood, Lauren M. Hickling, Bethany Hicks, Aroon D. Hingorani, Lee Howes, Ivie Itua, Victor Jardim, Wing-Yiu Jason Lee, Melaniepetra Jensen, Jessica Jones, Meleri Jones, George Joy, Vikas Kapil, Caoimhe Kelly, Hibba Kurdi, Jonathan Lambourne, Kai-Min Lin, Siyi Liu, Aaron Lloyd, Sarah Louth, Vineela Mandadapu, Katia Menacho, Celina Mfuko, Sebastian Millward, Oliver Mitchelmore, Christopher Moon, James Moon, Diana Muñoz Sandoval, Sam M. Murray, Ashley Otter, Susana Palma, Ruth Parker, Kush Patel, Mihaela Pawarova, Steffen E. Petersen, Brian Piniera, Franziska P. Pieper, Lisa Rannigan, Alicja Rapala, Amy Richards, Matthew Robathan, Joshua Rosenheim, Cathy Rowe, Matthew Royds, Jane Sackville West, Genine Sambile, Nathalie M. Schmidt, Hannah Selman, Andreas Seraphim, Mihaela Simion, Angelique Smit, Michelle Sugimoto, Leo Swadling, Stephen Taylor, Nigel Temperton, Stephen Thomas, George D. Thornton, Thomas A. Treibel, Art Tucker, Ann Varghese, Jessry Veerapen, Mohit Vijayakumar, Tim Warner, Sophie Welch, Hannah White, Theresa Wodehouse, Lucinda Wynne, and Dan Zahedi

Subjects
complement: immunoglobulin, SARS-CoV-2, vaccination, proteomics, COVID-19, variant of concern, Biotechnology, TP248.13-248.65, Biochemistry, QD415-436, Science
Abstract

Summary: Determining the protection an individual has to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants of concern (VoCs) is crucial for future immune surveillance, vaccine development, and understanding of the changing immune response. We devised an informative assay to current ELISA-based serology using multiplexed, baited, targeted proteomics for direct detection of multiple proteins in the SARS-CoV-2 anti-spike antibody immunocomplex. Serum from individuals collected after infection or first- and second-dose vaccination demonstrates this approach and shows concordance with existing serology and neutralization. Our assays show altered responses of both immunoglobulins and complement to the Alpha (B.1.1.7), Beta (B.1.351), and Delta (B.1.617.1) VoCs and a reduced response to Omicron (B1.1.1529). We were able to identify individuals who had prior infection, and observed that C1q is closely associated with IgG1 (r > 0.82) and may better reflect neutralization to VoCs. Analyzing additional immunoproteins beyond immunoglobulin (Ig) G, provides important information about our understanding of the response to infection and vaccination. Motivation: Assays for measuring serum antibody responses are typically limited to measurement of a total or single immunoglobulin isotype. The antibody response is far more complex, with multiple immunoglobulin classes, isotypes, and complement factors involved. This is a potential wealth of information that is typically understudied and missed by existing tests. The global COVID-19 pandemic has highlighted the need to understand better the immune response in respect to vaccine development and emerging new severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants. Using the ability of tandem mass spectrometry to multiplex and directly and accurately measure the antibody complex, we devised an alternative assay to capture this valuable information.

Published
2022
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5. Implementation and Extended Evaluation of the Euroimmun Anti-SARS-CoV-2 IgG Assay and Its Contribution to the United Kingdom’s COVID-19 Public Health Response

Author

Ashley David Otter, Abbie Bown, Silvia D’Arcangelo, Daniel Bailey, Amanda Semper, Jacqueline Hewson, Matthew Catton, Prem Perumal, Angela Sweed, Deborah Fox McKee, Jessica Jones, Heli Harvala, Abigail Lamikanra, Maria Zambon, Nick Andrews, Heather Whitaker, Ezra Linley, Alexander J. Mentzer, Donal Skelly, Julian C. Knight, Paul Klenerman, Gayatri Amirthalingam, Stephen Taylor, Cathy Rowe, Richard Vipond, and Tim Brooks

Subjects
SARS-CoV-2, assay development, coronavirus, immunoassays, neutralizing antibodies, Microbiology, QR1-502
Abstract

ABSTRACT In March 2020, the Rare and Imported Pathogens Laboratory at the UK Health Security Agency (UKHSA) (formerly Public Health England [PHE]) Porton Down, was tasked by the Department of Health and Social Care with setting up a national surveillance laboratory facility to study SARS-CoV-2 antibody responses and population-level sero-surveillance in response to the growing SARS-CoV-2 outbreak. In the following 12 months, the laboratory tested more than 160,000 samples, facilitating a wide range of research and informing UKHSA, DHSC, and UK government policy. Here we describe the implementation and use of the Euroimmun anti-SARS-CoV-2 IgG assay and provide an extended evaluation of its performance. We present a markedly improved overall sensitivity of 91.39% (≥14 days 92.74%, ≥21 days 93.59%) compared to our small-scale early study, and a specificity of 98.56%. In addition, we detail extended characteristics of the Euroimmun assay: intra- and interassay precision, correlation to neutralization, and assay linearity. IMPORTANCE Serology assays have been useful in determining those with previous SARS-CoV-2 infection in a wide range of research and serosurveillance projects. However, assays vary in their sensitivity at detecting SARS-CoV-2 antibodies. Here, we detail an extended evaluation and characterization of the Euroimmun anti-SARS-CoV-2 IgG assay, one that has been widely used within the United Kingdom on over 160,000 samples to date.

Published
2022
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6. mRNA vaccination in people over 80 years of age induces strong humoral immune responses against SARS-CoV-2 with cross neutralization of P.1 Brazilian variant

Author

Helen Parry, Gokhan Tut, Rachel Bruton, Sian Faustini, Christine Stephens, Philip Saunders, Christopher Bentley, Katherine Hilyard, Kevin Brown, Gayatri Amirthalingam, Sue Charlton, Stephanie Leung, Emily Chiplin, Naomi S Coombes, Kevin R Bewley, Elizabeth J Penn, Cathy Rowe, Ashley Otter, Rosie Watts, Silvia D'Arcangelo, Bassam Hallis, Andrew Makin, Alex Richter, Jianmin Zuo, and Paul Moss

Subjects
COVID-19, vaccination, immunosenescence, Medicine, Science, Biology (General), QH301-705.5
Abstract

Age is the major risk factor for mortality after SARS-CoV-2 infection and older people have received priority consideration for COVID-19 vaccination. However, vaccine responses are often suboptimal in this age group and few people over the age of 80 years were included in vaccine registration trials. We determined the serological and cellular response to spike protein in 100 people aged 80–96 years at 2 weeks after the second vaccination with the Pfizer BNT162b2 mRNA vaccine. Antibody responses were seen in every donor with high titers in 98%. Spike-specific cellular immune responses were detectable in only 63% and correlated with humoral response. Previous SARS-CoV-2 infection substantially increased antibody responses after one vaccine and antibody and cellular responses remained 28-fold and 3-fold higher, respectively, after dual vaccination. Post-vaccine sera mediated strong neutralization of live Victoria infection and although neutralization titers were reduced 14-fold against the P.1 variant first discovered in Brazil they remained largely effective. These data demonstrate that the mRNA vaccine platform delivers strong humoral immunity in people up to 96 years of age and retains broad efficacy against the P.1 variant of concern.

Published
2021
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7. Analogous humoral antigen recognition between Monkeypox-infected and Smallpox-vaccinated individuals

Author

Ashley D. Otter, Scott Jones, Bethany Hicks, Daniel Bailey, Helen Callaby, Catherine Houlihan, Tommy Rampling, Nicola Claire Gordon, Hannah Selman, Panayampalli S. Satheshkumar, Michael Townsend, Ravi Mehta, Marcus Pond, Rachael Jones, Deborah Wright, Clarissa Oeser, Simon Tonge, Ezra Linley, Georgia Hemingway, Tom Coleman, Sebastian Millward, Aaron Lloyd, Inger Damon, Tim Brooks, Richard Vipond, Cathy Rowe, and Bassam Hallis

Abstract

In early 2022, a cluster of Monkeypox (now termed MPOX) virus (MPXV) cases were identified within the UK with no prior travel history to MPXV-endemic regions, suggesting localised transmission of MPXV within the UK. Subsequently, cases were identified in several other non-endemic countries and currently exceed 80,000 worldwide, primarily affecting gay, bisexual, and other men who have sex with men. Public health agencies worldwide have offered the IMVANEX Smallpox vaccination to these individuals to provide protection and limit the spread of MPXV.We have developed a comprehensive array of ELISA assays to study poxvirus-induced antibodies, utilising 24 MPXV and 3 Vaccinia virus (VACV) recombinant antigens. Panels of serum samples from individuals with one, two, or three doses of IMVANEX or ACAM2000 (Modified Vaccinia Ankara (MVA)) vaccination, and those with prior MPOX infection were tested against these antigens, with Pearson correlation, principal component analysis and receiver operator curve statistics used to further elucidate antigenic responses to pox-virus infection. Furthermore, using our data, we demonstrated the development of a pooled antigen ELISA that can reliably detect antibody responses induced by Smallpox vaccination or MPXV infection.Using diverse poxvirus antigen ELISAs, we observe that one dose of Smallpox vaccination induces a low number of antibodies, primarily against MPXV B2, with a second dose inducing considerably higher antibody responses against B2R but also to other MPXV antigens such as B5, E8, M1, and A35. Prior MPXV infection, both Clades IIa and IIb, induce variable responses, but similarly induce antibody responses to poxvirus antigens observed in Smallpox-vaccinated individuals, and additionally responses to MPXV A27, A29 and H3. Principal component and Pearson correlation matrix identified MPXV A27 as a differential between IMVANEX and MPOX-infected individuals, whilst MPXV M1 (VACV L1) is likely a serological marker of IMVANEX-vaccination. When using recombinant MPXV/VACV protein homologues, we also observe a difference in antigen binding, with variability based on the individual’s originating infection/vaccination. Using a pooled-antigen ELISA, we also demonstrate a sensitivity of 97.14% (95% CI:91.93-99.22) and specificity of 98.23% (96.67-99.07) in detecting poxvirus antibodies with applicability to measuring longitudinal antibody responses post-vaccination/post-MPXV infection.Here, we show that both MPXV-infected or Smallpox-vaccinated individuals mount antibodies able to bind a diverse but core set of poxvirus antigens, with implications for future vaccine (e.g., mRNA-based) and therapeutic (e.g., monoclonal antibodies) targets. We identify low levels of antibodies observed in those post dose one IMVANEX, but considerably higher levels of antibodies post dose two. We also demonstrate that homologous VACV and MPXV antigens may offer a mechanism for discriminating between vaccinated and MPXV-infected individuals through differential binding, aiding in serosurveillance and future immunology studies.

Published
2022

8. Comparability of six different immunoassays measuring <scp>SARS‐CoV</scp> ‐2 antibodies with neutralizing antibody levels in convalescent plasma: From utility to prediction

Author

Maria Zambon, Abigail Lamikanra, Tim Brooks, Sarah Williams, Annabelle Mai, Marta S Oliveira, Emma M. Bentley, Kimberly Gilmour, Robin Gopal, Jusvinder Dadhra, Sheba Ziyenge, Cathy Rowe, Julie Huiyuan Xiao, Mabel Csatari, Pat Tsang, Rutger Ploeg, Dung Nguyen, David J. Roberts, Alain Townsend, Peter Simmonds, Heli Harvala, and Ashley Otter

Subjects
Hemagglutination, Immunology, Antibodies, Viral, medicine.disease_cause, Neutralization, COVID-19 Serological Testing, Neutralization Tests, intravenous immunoglobulin, medicine, Humans, Immunology and Allergy, Potency, infectious disease testing, Neutralizing antibody, COVID-19 Serotherapy, Coronavirus, Immunoassay, biology, SARS-CoV-2, business.industry, Brief Report, Immunization, Passive, COVID-19, Hematology, Antibodies, Neutralizing, Virology, In vitro, Titer, biology.protein, Brief Reports, Antibody, business
Abstract

Background Convalescent plasma (CP) therapy for coronavirus disease (COVID‐19) provides virus‐neutralizing antibodies that may ameliorate the outcome of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infections. The effectiveness of CP likely depends on its antiviral neutralizing potency and is determined using in vitro neutralizing antibody assays. Study design and methods We evaluated abilities of three immunoassays for anti‐spike antibodies (EUROimmun, Ortho, Roche), a pseudotype‐based neutralization assay, and two assays that quantify ACE2 binding of spike protein (GenScript and hemagglutination test [HAT]‐based assay) to predict neutralizing antibody titers in 113 CP donations. Assay outputs were analyzed through linear regression and calculation of sensitivities and specificities by receiver operator characteristic (ROC) analysis. Results Median values of plasma samples containing neutralizing antibodies produced conversion factors for assay unitage of ×6.5 (pseudotype), ×19 (GenScript), ×3.4 (HAT assay), ×0.08 (EUROimmun), ×1.64 (Roche), and ×0.10 (Ortho). All selected assays were sufficient in identifying the high titer donations based on ROC analysis; area over curve ranged from 91.7% for HAT and GenScript assay to 95.6% for pseudotype assay. However, their ability to predict the actual neutralizing antibody levels varied substantially as shown by linear regression correlation values (from 0.27 for Ortho to 0.61 for pseudotype assay). Discussion Overall, the study data demonstrate that all selected assays were effective in identifying donations with high neutralizing antibody levels and are potentially suitable as surrogate assays for donation selection for CP therapy.

Published
2021

9. Immune boosting by B.1.1.529

Author

Catherine J, Reynolds, Corinna, Pade, Joseph M, Gibbons, Ashley D, Otter, Kai-Min, Lin, Diana, Muñoz Sandoval, Franziska P, Pieper, David K, Butler, Siyi, Liu, George, Joy, Nasim, Forooghi, Thomas A, Treibel, Charlotte, Manisty, James C, Moon, Amanda, Semper, Tim, Brooks, Áine, McKnight, Daniel M, Altmann, Rosemary J, Boyton, Hakam, Abbass, Aderonke, Abiodun, Mashael, Alfarih, Zoe, Alldis, Oliver E, Amin, Mervyn, Andiapen, Jessica, Artico, João B, Augusto, Georgina L, Baca, Sasha N L, Bailey, Anish N, Bhuva, Alex, Boulter, Ruth, Bowles, Olivia V, Bracken, Ben, O'Brien, Natalie, Bullock, Gabriella, Captur, Olivia, Carr, Nicola, Champion, Carmen, Chan, Aneesh, Chandran, Tom, Coleman, Jorge, Couto de Sousa, Xose, Couto-Parada, Eleanor, Cross, Teresa, Cutino-Moguel, Silvia, D'Arcangelo, Rhodri H, Davies, Brooke, Douglas, Cecilia, Di Genova, Keenan, Dieobi-Anene, Mariana O, Diniz, Anaya, Ellis, Karen, Feehan, Malcolm, Finlay, Marianna, Fontana, Sasha, Francis, David, Gillespie, Derek, Gilroy, Matt, Hamblin, Gabrielle, Harker, Georgia, Hemingway, Jacqueline, Hewson, Wendy, Heywood, Lauren M, Hickling, Bethany, Hicks, Aroon D, Hingorani, Lee, Howes, Ivie, Itua, Victor, Jardim, Wing-Yiu Jason, Lee, Melaniepetra, Jensen, Jessica, Jones, Meleri, Jones, Vikas, Kapil, Caoimhe, Kelly, Hibba, Kurdi, Jonathan, Lambourne, Aaron, Lloyd, Sarah, Louth, Mala K, Maini, Vineela, Mandadapu, Katia, Menacho, Celina, Mfuko, Kevin, Mills, Sebastian, Millward, Oliver, Mitchelmore, Christopher, Moon, James, Moon, Sam M, Murray, Mahdad, Noursadeghi, Ashley, Otter, Susana, Palma, Ruth, Parker, Kush, Patel, Mihaela, Pawarova, Steffen E, Petersen, Brian, Piniera, Lisa, Rannigan, Alicja, Rapala, Amy, Richards, Matthew, Robathan, Joshua, Rosenheim, Cathy, Rowe, Matthew, Royds, Jane, Sackville West, Genine, Sambile, Nathalie M, Schmidt, Hannah, Selman, Andreas, Seraphim, Mihaela, Simion, Angelique, Smit, Michelle, Sugimoto, Leo, Swadling, Stephen, Taylor, Nigel, Temperton, Stephen, Thomas, George D, Thornton, Art, Tucker, Ann, Varghese, Jessry, Veerapen, Mohit, Vijayakumar, Tim, Warner, Sophie, Welch, Hannah, White, Theresa, Wodehouse, Lucinda, Wynne, Dan, Zahedi, and Benjamin, Chain

Subjects
B-Lymphocytes, Mice, SARS-CoV-2, T-Lymphocytes, Spike Glycoprotein, Coronavirus, Immunization, Secondary, Animals, COVID-19, Humans, Cross Reactions, Antibodies, Viral, Antibodies, Neutralizing, BNT162 Vaccine
Abstract

The Omicron, or Pango lineage B.1.1.529, variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) carries multiple spike mutations with high transmissibility and partial neutralizing antibody (nAb) escape. Vaccinated individuals show protection against severe disease, often attributed to primed cellular immunity. We investigated T and B cell immunity against B.1.1.529 in triple BioNTech BNT162b2 messenger RNA-vaccinated health care workers (HCWs) with different SARS-CoV-2 infection histories. B and T cell immunity against previous variants of concern was enhanced in triple-vaccinated individuals, but the magnitude of T and B cell responses against B.1.1.529 spike protein was reduced. Immune imprinting by infection with the earlier B.1.1.7 (Alpha) variant resulted in less durable binding antibody against B.1.1.529. Previously infection-naïve HCWs who became infected during the B.1.1.529 wave showed enhanced immunity against earlier variants but reduced nAb potency and T cell responses against B.1.1.529 itself. Previous Wuhan Hu-1 infection abrogated T cell recognition and any enhanced cross-reactive neutralizing immunity on infection with B.1.1.529.

Published
2022

10. Casirivimab and imdevimab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial

Author

Obbina Abani, Ali Abbas, Fatima Abbas, Mustafa Abbas, Sadia Abbasi, Hakam Abbass, Alfie Abbott, Nabeel Abdallah, Ashraf Abdelaziz, Mohamed Abdelfattah, Bushra Abdelqader, Basir Abdul, Althaf Abdul Rasheed, Ajibode Abdulakeem, Rezan Abdul-Kadir, Abdullah Abdullah, Abdulfatahi Abdulmumeen, Rasheed Abdul-Raheem, Niyaz Abdulshukkoor, Kula Abdusamad, Yazeed Abed El Khaleq, Mai Abedalla, Abeer Ul-Amna, Katrina Abernethy, Adebanke Aboaba, Hani Abo-Leyah, Ahmed Abou-Haggar, Mahmoud Abouibrahim, Miriam Abraham, Tizzy Abraham, Abraheem Abraheem, Judith Abrams, Hyacinth-John Abu, Ahmed Abu-Arafeh, Syed M Abubacker, Akata Abung, Yaa Aceampong, Amaka Achara, Devikumar Acharya, Sarah Acheampong, Janet Acheson, Andres Acosta, Catherine Acton, Jacqueline Adabie-Ankrah, Fiona Adam, Matthew Adam, Huzaifa Adamali, Carol Adams, Charlotte Adams, Kate Adams, Richard Adams, Tim Adams, Krishma Adatia, Kirsty Adcock, Ade Adebiyi, Ken Adegoke, Vicki Adell, Sherna Adenwalla, Oluwasegun A Adesemoye, Emmanuel O Adewunmi, Joyce Adeyemi, Binay Adhikari, Rina Adhikary, Gabrielle Adkins, Adnan Adnan, John Aeron-Thomas, Debbie Affleck, Carmel Afnan, Muhammad Afridi, Zainab A Aftab, Meenakshi Agarwal, Rachel Agbeko, Chris Agbo, Sunil Aggarwal, Arameh Aghababaie, Shafana Ahamed Sadiq, Mohamed H Ahammed Nazeer, Mohammad Ahmad, Syed Ahmad, Asim Ahmed, Bilal Ahmed, Forizuddin Ahmed, Hamze Ahmed, Irshad Ahmed, Khaled Ahmed, Liban Ahmed, Mahin Ahmed, Maria C Ahmed, Muhammad S Ahmed, Naseer Ahmed, Nausheen Ahmed, Osama Ahmed, Rajia A Ahmed, Rizwan Ahmed, Saif Ahmed, Sammiya Ahmed, Syed Ahmed, Syed Haris Ahmed, Roa Ahmed Ali, Sana Ahmed, Sana Ahmer, Dhiraj Ail, Mark Ainsworth, Myriam Aissa, Lindianne Aitken, Bini Ajay, Abdulakeem Ajibode, Ayesha Ajmi, Nasim Akhtar, Nauman Akhtar, Suha Akili, Oludoyinsola Akindolie, Yinka Akinfenwa, Olugbenga Akinkugbe, Ibrahim Akinpelu, Olugbenro Aktinade, Ahmad S A R Al Aaraj, Asma Al Balushi, Majd Al Dakhola, Aladdin Al Swaifi, Eslam Al-Abadi, Narendra Aladangady, Ayaz Alam, Sajid Alam, Abbas Al-Asadi, Kyriaki Alatzoglou, Paul Albert, Lorraine Albon, Gemma Alcorn, Stephen Alcorn, Aggie Aldana, David Alderdice, Rayan Aldouri, Jonathan Aldridge, Nicolas Aldridge, Ana Alegria, Alison Alexander, John Alexander, Peter D G Alexander, Julyan Al-Fori, Laith Alghazawi, Bahij Al-Hakim, Shams Al-Hity, Ali Ali, Asad Ali, Fawzia R Ali, Jawad Ali, Mariam Ali, Mohammad Ali, Nayab Ali, Oudai Ali, Sakina Ali, Syed Ali, Abid Alina, Fine Aliyuda, Katrin Alizadeh, Maithem Al-Jibury, Saba Al-Juboori, Majid Al-Khalil, Moutaz Alkhusheh, Fiona Allan, Alison Allanson, Robert Allcock, Eireann Allen, Kerry Allen, Louise Allen, Poppy Allen, Rebecca Allen, Sam Allen, Sharon Allen, Simon Allen, Kathryn Allison, Bethan Allman, Lynne Allsop, Hassan Al-Moasseb, Magda Al-Obaidi, Lina Alomari, Akram Al-Rabahi, Bahar Al-Ramadhani, Zayneb Al-Saadi, Inji Alshaer, Rustam Al-Shahi Salman, Warkaq Al-Shamkhani, Bashar Al-Sheklly, Sara Altaf, Mary Alvarez, Maysaa Alzetani, Susan Amamou, Noor Amar, Sakkarai Ambalavanan, Robert Ambrogetti, Chris Ambrose, Amir Ameen, Maria R Amezaga, Allison Amin, Amina Amin, Kanish Amin, Syed Amin, Tara Amin, Amjad Amjad, Neelma Amjad, Victoria Amosun, Khaled Amsha, Pugh Amy, Atul Anand, Samantha Anandappa, Julie Anderson, Laura Anderson, Michelle Anderson, Nicola Anderson, Rachel Anderson, Rory Anderson, Wendy Anderson, Prematie Andreou, Angela Andrews, Antonette Andrews, Jill Andrews, Kanayochukwu Aneke, Andrew Ang, Wan Wei Ang, Tammy Angel, Aramburo Angela, Paola Angelini, Lazarus Anguvaa, Oleg Anichtchik, Millicent Anim-Somuah, Krishnan Aniruddhan, Jessica Annett, Louise Anning, Patrick J Anstey, Rebekah Anstey, Alpha Anthony, Aaron Anthony-Pillai, Philip Antill, Zhelyazkova Antonina, Varghese Anu, Muhammad Anwar, Aristeidis Apostolopoulos, Sarah Appleby, Diane Appleyard, Maia Far Aquino, Bianca Araba, Samuel Aransiola, Mariana Araujo, Ann Archer, Denise Archer, Simon Archer, Christian Ardley, Ana-Maria Arias, Ryoki Arimoto, Charlotte Arkley, Charlotte Armah, Ilianna Armata, Adam Armitage, Ceri Armstrong, Maureen Armstrong, Sonia Armstrong, Philippa Armtrong, Heike Arndt, Clare Arnison-Newgass, David Arnold, Rachael Arnold, Dhawal Arora, Kavan Arora, Pardeep Arora, Rishi Arora, Arslam Arter, Ayush Arya, Rita Arya, Denisa Asandei, Adeeba Asghar, Catherine Ashbrook-Raby, Helen Ashby, Jan Ashcroft, John Ashcroft, Samuel Ashcroft, Georgia Asher, Ayesha Ashfaq, Abdul Ashish, Sally Ashman-Flavell, Sundar Ashok, Abd-El-Aziz Ashour, Muhammad Z Ashraf, Saima Ashraf, Mohammad B Ashraq, Deborah Ashton, Susan Ashton, Andrew Ashworth, Rebecca Ashworth, Arshia Aslam, Harshini Asogan, Atif Asrar, Omar Assaf, Raine Astin-Chamberlain, Deborah Athorne, Billie Atkins, Christopher Atkins, Stacey Atkins, John Atkinson, Vicki Atkinson, Brygitta Atraskiewicz, Abdul A Attia, Paula Aubrey, Avinash Aujayeb, Aye CT Aung, Hnin Aung, Kyaw T Aung, Yin Aung, Zaw M Aung, Emily Austin, Karen Austin, Abdusshakur Auwal, Miriam Avery, Nicholas Aveyard, Joanne Avis, Georgina Aviss, Cristina Avram, Paula Avram, Gabriel Awadzi, Atia Awan, Aszad Aya, Eman Ayaz, Amanda Ayers, Jawwad Azam, Mohammed Azharuddin, Ghazala Aziz, N Aziz, Ali Azkoul, Ashaari Azman Shah, Giada Azzopardi, Hocine Azzoug, Fiyinfoluwa Babatunde, Melvin Babi, Babiker Babiker, Gayna Babington, Matthew Babirecki, Marta Babores, Adetona O Babs-Osibodu, Sammy Bacciarelli, Roudi Bachar, Gina Bacon, Jenny Bacon, Bibi Badal, Gurpreet R Badhan, Shreya Badhrinarayanan, Joseph P Bae, Alice Baggaley, Amy Baggott, Graham Bagley, Dinesh Bagmane, Lynsey Bagshaw, Kasra Bahadori, James Bailey, Katie Bailey, Lindsey Bailey, Liz Bailey, Morgan Bailey, Pippa Bailey, Sarah Bailey, Hamish Baillie, J Kenneth Baillie, Jennifer Bain, Vikram Bains, David Baird, Kevin Baird, Susan Baird, Tracy Baird, Yolanda Baird, Aiysha Bajandouh, Evelyn Baker, Johanne Baker, Josephine Baker, Kenneth Baker, Rebecca Baker, Terri-Anne Baker, Victoria Baker, Hugh Bakere, Nawar Bakerly, Michelle Baker-Moffatt, Nauman Bakhtiar, Panos Bakoulas, Niranjan Balachandran, Andrea Balan, Theodosios Balaskas, Madhu Balasubramaniam, Alison Balcombe, Alexander Baldwin, Ashley Baldwin, Caron Baldwin, Danielle Baldwin, Rebekah Baldwin-Jones, James Balfour, Matthew Ball, K Ballard, Ismael Balluz, Craig Balmforth, Emese Balogh, Amir Baluwala, Gabby Bambridge, Alasdair Bamford, Amy Bamford, Peter Bamford, Adefunke Bamgboye, Elizabeth Bancroft, Hollie Bancroft, Joyce Banda, Krishna Bandaru, Srini Bandi, Nageswar Bandla, Somaditya Bandyopadhyam, Amit Banerjee, Ritwik Banerjee, Harrison Banks, Luke Banks, Paul Banks, Oliver Bannister, Laura Banton, Tran Bao, Mariamma Baptist, Tanya Baqai, Ananya M Baral, Desislava Baramova, Russel Barber, Emma Barbon, Miriam Barbosa, Monica Barbosa, Jamie Barbour, Alexander Barclay, Claire Barclay, George Bardsley, Stephanie Bareford, Shahedal Bari, Morris Barimbing, Amy Barker, Debbie Barker, Helen Barker, Joseph Barker, Leon Barker, Oliver Barker, Kerry Barker-Williams, Sinha Barkha, Juliana Barla, Gavin Barlow, Richard Barlow, Valerie Barlow, James Barnacle, Alex Barnard, Debi Barnes, Nicky Barnes, Theresa Barnes, Calum Barnetson, Amy Barnett, Ashton Barnett-Vanes, William Barnsley, Andrew Barr, David Barr, Shaney Barratt, Manuella Barrera, Amy Barrett, Fiona Barrett, Jessica Barrett, Jazz Bartholomew, Claire Bartlett, Georgina Bartlett, Greg Barton, Jill Barton, Lorna Barton, Rachael Barton, Rosaleen Baruah, Sonia Baryschpolec, Archana Bashyal, Betsy Basker, Buddha Basnyat, Ayten Basoglu, John Bassett, G Bassett, Chris Bassford, Bengisu Bassoy, Victoria Bastion, Anup Bastola, Anupam Basumatary, Tristan Bate, Harry J Bateman, Kathryn Bateman, Vhairi Bateman, Eleanor Bates, Hayley Bates, Michelle Bates, Simon Bates, Sally Batham, Ana Batista, Amit Batla, Dushyant Batra, Harry Batty, Thomas Batty, Miranda Baum, Rachel Baumber, Carina Bautista, Fareha Bawa, Fatima S Bawani, Simon Bax, Matt Baxter, Nicola Baxter, Zachary Baxter, Hannah Bayes, Farid Bazari, Rohit Bazaz, Ahmad Bazli, Laura Beacham, Wendy Beadles, Philip Beak, Andy Beale, Jack Bearpark, Karen Beaumont, Dawn Beaumont-Jewell, Theresa Beaver, Sarah Beavis, Christy Beazley, Sarah Beck, Virginia Beckett, Rosie Beckitt, Heidi Beddall, Seonaid Beddows, Deborah Beeby, Gail Beech, Michelle Beecroft, Sally Beer, Jane Beety, Gabriela Bega, Alison Begg, Susan Begg, Sara Beghini, Ayesha Begum, Salman Begum, Selina Begum, Teresa Behan, Roya Behrouzi, Jon Beishon, Claire Beith, James Belcher, Holly Belfield, Katherine Belfield, Ajay Belgaumkar, Dina Bell, Gareth Bell, Gillian Bell, Lauren Bell, Louise Bell, Nicholas Bell, Pippa Bell, Stephanie Bell, Jennifer L Bell, Jennifer Bellamu, Mary Bellamy, Arianna Bellini, Amanda Bellis, Fionn Bellis, Lesley Bendall, Naveena Benesh, Nicola Benetti, Leonie Benham, Guy Benison-Horner, Ann Bennett, Caroline Bennett, Gillian Bennett, Kristopher Bennett, Lorraine Bennett, Sara Bennett, Karen Bennion, Vivienne Benson, Andrew Bentley, James Bentley, Ian Benton, Eva Beranova, Matthew Beresford, Colin Bergin, Malin Bergstrom, Jolanta Bernatoniene, Thomas Berriman, Zoe Berry, Kimberley Best, Ans-Mari Bester, Yvonne Beuvink, Emily Bevan, Sarah Bevins, Tom Bewick, Andrew Bexley, Sonay Beyatli, Fenella Beynon, Arjun Bhadi, Sanjay Bhagani, Shiv Bhakta, Rekha Bhalla, Khushpreet Bhandal, Kulbinder Bhandal, Ashwin Bhandari, Sangam Bhandari, Aashutosh Bhanot, Ravina Bhanot, Prashanth Bhat, Rahul Bhatnagar, Karan Bhatt, Janki Bhayani, Deepika Bhojwani, Salimuzzaman Bhuiyan, Anna Bibby, Fatima Bibi, Naheeda Bibi, Salma Bibi, Tihana Bicanic, Sarah Bidgood, Julie Bigg, Sarah Biggs, Alphonsa Biju, Andras Bikov, Sophie Billingham, Jessica Billings, Alice Binns, Muhammad BinRofaie, Oliver Bintcliffe, Catherine Birch, Jenny Birch, Katherine Birchall, Sam Bird, Sumedha Bird, Mark Birt, Kilanalei Bishop, Linda Bishop, Lisa Bishop, Karen Bisnauthsing, Nibedan Biswas, Sahar Biuk, Karen Blachford, Ethel Black, Helen Black, Karen Black, Mairead Black, Polly Black, Hayley Blackgrove, Bethan Blackledge, Joanne Blackler, Samantha Blackley, Helen Blackman, Caroline Blackstock, Francesca Blakemore, Helen Blamey, Alison Bland, Sujata Blane, Simon Blankley, Parry Blaxill, Katie Blaylock, Jane Blazeby, Natalie Blencowe, Ben Bloom, Jack Bloomfield, Angela Bloss, Hannah Bloxham, Louise Blundell, Andrew Blunsum, Mark Blunt, Ian Blyth, Kevin Blyth, Andrew Blythe, Karen Blythe, Marilyn Boampoaa, Boniface Bobie, Karen Bobruk, Pritesh N Bodalia, Neena Bodasing, Tanya Bodenham, Gabriele Boehmer, Marta Boffito, Kristyna Bohmova, Niamh Bohnacker, Sumit Bokhandi, Maria Bokhar, Saba Bokhari, Sakina Bokhari, Syed O Bokhari, Ambrose Boles, Charlotte Bond, Helena Bond, Stuart Bond, Thomas Bond, Alice Bone, Georgia Boniface, Lizzy Bonney, Sarah Boot, Joanne Borbone, Naomi Borman, Mamu Boshir, Fiona Bottrill, Laura Bough, Hayley Boughton, Zoe Boult, Miriam Bourke, Stephen Bourke, Michelle Bourne, Rachel Bousfield, Lucy Boustred, Alexandra Bowes, Amy Bowes, Philip Bowker, Louise Bowman, Simon Bowman, Rachel Bowmer, Angie Bowring, Helen Bowyer, Aileen Boyd, Jenny Boyd, Laura Boyd, Namoi Boyle, Pauline Boyle, Rosalind Boyle, Louise Boyles, Leanna Brace, Jodie Bradder, Clare J Bradley, Pamela Bradley, Patrick Bradley, Paul Bradley, Joanne Bradley-Potts, Lynne Bradshaw, Zena Bradshaw, Rebecca Brady, Shirin Brady, Denise Braganza, Marie Branch, Thomas Brankin-Frisby, Jamie Brannigan, Sophie Brattan, Fiona Bray, Nancy Bray, Manny Brazil, Lucy Brear, Tracy Brear, Stephen Brearey, Laura Bremner, Morwenna Brend, Giovanna Bretland, Chris Brewer, Gavin Bridgwood, Sara Brigham, John Bright, Chris Brightling, Lutece Brimfield, Elaine Brinkworth, Robin Brittain-Long, Vianne Britten, Lauren Broad, Sarah Broad, Rosie Broadhurst, Andrew Broadley, Marie Broadway, Christopher Brockelsby, Megan Brocken, Tomos Brockley, Mary Brodsky, Fiona Brogan, Liz Brohan, Felicity Brokke, Jacob Brolly, David Bromley, Hannah Brooke-Ball, Verity Brooker, Matthew Brookes, Deirdre Brooking, Alison Brooks, Karen Brooks, Nicole Brooks, Philip Brooks, Rachel Brooks, Sophie Brooks, Tim Brooks, Natalie Broomhead, Chloe Broughton, Nathaniel Broughton, Matt Brouns, Alison Brown, Ammani Brown, Carly Brown, Catrin Brown, Ellen Brown, Heather Brown, Janet Brown, Louise Brown, Niall Brown, Pauline Brown, Rachel Brown, Richard Brown, Robert Brown, Steven Brown, Thomas Brown, Tom Brown, Bria Browne, Charlotte Browne, Duncan Browne, Mitchell Browne, Stephen Brownlee, Alba Brraka, Johanna Bruce, Michelle Bruce, Wojciech Brudlo, Nigel Brunskill, Alan Brunton, Margaret Brunton, Meera Bryant, April Buazon, Maya H Buch, Ruaridh Buchan, Ruaridh Buchanan, Danielle Buche, Amanda Buck, Matthew Buckland, Laura Buckley, Philip Buckley, Sarah Buckley, Carol Buckman, George Bugg, Ramadan Bujazia, Marwan Bukhari, Shanze Bukhari, Richard Bulbulia, Alex Bull, Damian Bull, Rhian Bull, Thomas Bull, Naomi Bulteel, Kasun Bumunarachchi, Roneleeh Bungue-Tuble, Caroline Burchett, Dorota Burda, Christy Burden, Thomas G Burden, Mika Burgess, Richard Burgess, Sophia Burgess, Adrian Burman, Sara Burnard, Caroline Burnett, Amy Burns, Collette Burns, James Burns, Karen Burns, Daniel Burrage, Kate Burrows, Claire Burston, Ben Burton, Fiona Burton, Matthew Burton, Deborah Butcher, Aaron Butler, Jessica Butler, Joanne Butler, Joshua Butler, Peter Butler, Susan Butler, Al-Tahoor Butt, Mohammad M Butt, Caryl Butterworth, Nicola Butterworth-Cowin, Robert Buttery, Tom Buttle, Heather Button, Daniel Buttress, Jane Byrne, Wendy Byrne, Victoria Byrne-Watts, Amanda Cabandugama, Ruth Cade, Anthony Cadwgan, Ajeng Cahyareny, Donna Cairney, James Calderwood, Darren Caldow, Giorgio Calisti, Debbie Callaghan, Jennifer Callaghan, Claire Callens, Donaldson Callum, Caroline Calver, Melissa Cambell-Kelly, Tracey Camburn, David R Cameron, Eleanor Cameron, Fraser Cameron, Sarah Cameron, Sheena Cameron, Christian Camm, Renee F D Cammack, Alison Campbell, Amy Campbell, Barbara Campbell, Bridget Campbell, Debbie Campbell, Helen Campbell, Hilary Campbell, Jonathan Campbell, Mark Campbell, Robyn Campbell, Wynny Campbell, Quentin Campbell Hewson, Julie Camsooksai, Lisa Canclini, Shaula M Candido, Janie Candlish, Cielito Caneja, Alexandra Cann, Johnathon Cann, Ruby Cannan, Emma Cannon, Michael Cannon, Petra Cannon, Vivienne Cannons, Jane Cantliff, Ben Caplin, Santino Capocci, Noemi Caponi, Angelika Capp, Thomas Capstick, Mary Cardwell, Rachel Carey, Simon Carley, Tammy Carlin, Samantha Carmichael, Mandy Carnahan, Charlotte Caroline, Jodi Carpenter, Sharon Carr, Anna Carrasco, Zoe Carrington, Amy Carroll, Paul Carroll, Jonathan Carter, Michael Carter, Paul Carter, Penny Carter, Douglas Cartwright, Jo-Anne Cartwright, Claire Carty, Jaime Carungcong, Susan Casey, Annie Cassells, Teresa Castiello, Gail Castle, Bridget Castles, Melanie Caswell, Ana Maria Catana, Heidi Cate, Susanne Cathcart, Katrina Cathie, Christine Catley, Laura Catlow, Matthew Caudwell, Anna Cavazza, Luke Cave, Simon Cavinato, Frianne Cawa, Kathryn Cawley, Chloe Caws, Hankins Cendl, Hannah Century, Jeva Cernova, Mansur Cesay, Ed Cetti, Stephanie Chabane, Manish Chablani, Cathleen Chabo, David Chadwick, Julie Chadwick, Robert Chadwick, Ela Chakkarapani, Arup Chakraborty, Mallinath Chakraborty, Mollika Chakravorty, Bimal Chalise, James Chalmers, Richard Chalmers, Georgina Chamberlain, Sarah Chamberlain, Emma Chambers, Jonathan Chambers, Lucy Chambers, Naomi Chambers, Alex Chan, Carmen Chan, Cheuk Chan, Evelyn Chan, Kayen Chan, Kimberley Chan, Ping Chan, Rebekah (Pui-Ching) Chan, Xin Hui S Chan, Chris Chandler, Heidi Chandler, Kim J Chandler, Stuart Chandler, Zoe Chandler, Sumit Chandra, Navin Chandran, Badrinathan Chandrasekaran, Yvonne Chang, Josephine Chaplin, Graeme Chapman, John Chapman, Katie Chapman, Laura Chapman, Lianne Chapman, Polly Chapman, Timothy Chapman, Lucy C Chappell, Lucy Chappell, Amanda Charalambou, Bethan Charles, Dianne Charlton, Kevin Chatar, Calvin Chatha, Ritesh Chaube, Muhammad Y N Chaudhary, Iram Chaudhry, Nazia Chaudhuri, Muhammad Chaudhury, Anoop Chauhan, Ruchi Singh Chauhan, Nicola Chavasse, Vipal Chawla, Lindsay Cheater, James Cheaveau, Charlotte Cheeld, Michelle Cheeseman, Fang Chen, Hui Min Chen, Terence Chen, Floria Cheng, Lok Yin Cheng, Zhihang Cheng, Helen Chenoweth, Chun How Cheong, Shiney Cherian, Mary Cherrie, Helen Cheshire, Chee Kay Cheung, Elaine Cheung, Michelle Cheung, Claire Cheyne, Swati Chhabra, Wei Ling Chia, Eric Chiang, Angela Chiapparino, Rosavic Chicano, Zviedzo A Chikwanha, Sam Chilcott, Phillipa Chimbo, KokWai Chin, Wen Jie Chin, Rumbidzai Chineka, Amol Chingale, Heather Chisem, Claire Chisenga, Ben Chisnall, Carolyn Chiswick, Sunder Chita, Nihil Chitalia, Matthew Chiu, Brenda Chivima, Catherine Chmiel, Soha Choi, Willy Choon Kon Yune, Vandana Choudhary, Sarah Choudhury, Bing-Lun Chow, Mahibbur Chowdhury, Shahid Chowdhury, Victoria Christenssen, Peter Christian, Alexander Christides, Fiona Christie, Daniel Christmas, Thereza Christopherson, Mark Christy, Paris Chrysostomou, Yunli Chua, Dip Chudgar, Richard Chudleigh, Srikanth Chukkambotla, Michael Eze Chukwu, Izu Chukwulobelu, Chi Yee Chung, Elaine Church, Sara R Church, David Churchill, Nicole Cianci, Nick Ciccone, Paola Cicconi, Paola Cinardo, Zdenka Cipinova, Bessie Cipriano, Sarah Clamp, Melanie Clapham, Edel Clare, Sarbjit Clare, Andrew Clark, Charlotte Clark, Diane Clark, Felicity Clark, Gabrielle Clark, James Clark, Katherine Clark, Kaylea Clark, Louise Clark, Lucy Clark, Matthew Clark, Patricia Clark, Richard Clark, Thomas Clark, Zoe Clark, Andrea Clarke, Paul Clarke, Robert Clarke, Roseanne Clarke, Samantha Clarke, Sheron Clarke, Alleyna Claxton, Kate Clay, Elizabeth Clayton, Olivia Clayton, Jill Clayton-Smith, Chris Cleaver, Carlota Clemente de la Torre, Jayne Clements, Suzanne Clements, Francesca Clemons, Rachael Clifford, Sarah Clifford, Amelia Clive, Jonathan Clouston, Samantha Clueit, Andrea Clyne, Michelle Coakley, Peter G L Coakley, Kathryn Cobain, Alexandra Cochrane, Patricia Cochrane, Maeve Cockerell, Helen Cockerill, Shirley Cocks, Rachel Codling, Adam Coe, Samantha Coetzee, David Coey, Danielle Cohen, Jonathan Cohen, Oliver Cohen, David Cohen, Mike Cohn, Louise Coke, Olutoyin Coker, Nicholas Colbeck, Roghan Colbert, Esther Cole, Jade Cole, Joby Cole, Garry Coleman, Matt Coleman, Tom Coleman, Holly Coles, Macleod Colin, Alicia Colino-Acevedo, Julie Colley, Dawn Collier, Heather Collier, Paul Collini, Emma Collins, Jaimie Collins, Joanne Collins, Nicola Collins, Sally Collins, Vicky Collins, Andrew Collinson, Bernadette Collinson, Jennifer Collinson, Matthew Collis, Madeleine Colmar, Hayley E Colton, James Colton, Katie Colville, Carolyn Colvin, Edward Combes, David Comer, Alison Comerford, Dónal Concannon, Robin Condliffe, Lynne Connell, Natalie Connell, Karen Connelly, Gavin Connolly, Emma Connor, Antonia Conroy, Veronica Conteh, Rory Convery, Francesca Conway, Grainne Conway, Rhiannon Conway, Jo-Anna Conyngham, Colette Cook, Eloise Cook, Gemma Cook, Helen Cook, Julie Cook, Danielle Cooke, Graham Cooke, Katrina Cooke, Tim Cooke, Adele Cooper, Chris Cooper, David Cooper, Helen Cooper, Jamie Cooper, Lauren Cooper, Nick Cooper, Rowena Cooper, Thomas Cope, Sinead Corbet, Carolyn Corbett, John Corcoran, Chris Cordell, Jessica Cordle, Alasdair Corfield, John Corless, Alison Corlett, Joe Cornwell, Michael Cornwell, Diana Corogeanu, Mirella Corredera, Ruth Corrigan, P Corry, Rita Corser, Denise Cosgrove, Tracey Cosier, Patricia Costa, Charlie Coston, Susannah Cotgrove, Zoe Coton, Lisa-Jayne Cottam, Rhiannon Cotter, Donna Cotterill, Caroline Cotton, Andrew Coull, James Coulson, David Counsell, David Counter, Cherry Coupland, Ellie Courtney, Julia Courtney, Rebecca Cousins, Alexander Cowan, Elena Cowan, Richard Cowell, Louise Cowen, Steve Cowman, Amanda Cowton, Ellie Cox, Giles Cox, Karina Cox, Miriam Cox, Karen Coy, Andrea Cradduck-Bamford, Victoria Craig, Felicity Craighead, Matthew Cramp, Jacolene Crause, Angie Crawford, Emma Crawford, Isobel Crawford, Sarah Crawshaw, Ben Creagh-Brown, Andrew Creamer, Joanne Cremona, Saveria Cremona, Janet Cresswell, Mark Cribb, Charles Crichton, Declan Crilly, Lauren Crisp, Nikki Crisp, Dominic Crocombe, Maria Croft, Derrick Crook, Jennifer Crooks, Harriet Crosby, Elizabeth Cross, Ellie Cross, Sarah Cross, Tim Cross, Amy Crothers, Stephen Crotty, Susan Crouch, Madeleine Crow, Amanda Crowder, Kate Crowley, Teresa Crowley, Rebecca Croysdill, Callum Cruickshank, Conor Cruickshank, Irena Cruickshank, James Cruise, Carina Cruz, Trino Cruz Cervera, Dominic Cryans, Guanguo Cui, Helen Cui, Lorraine Cullen, Gillian Cummings-Fosong, Victoria Cunliffe, Neil Cunningham, Nicola Cunningham, Jason Cupitt, Hollie Curgenven, Gerens Curnow, David Curran, Simon Curran, Craig Currie, Jacqueline Currie, Scarlett Currie, Jonathan Curtis, Katrina Curtis, Olivia Curtis, Thomas Curtis, Rebecca Cuthbertson, Sean Cutler, Marta Czekaj, Patrycja Czylok, Silvia D'Arcangelo, Joana da Rocha, Andrew Dagens, Helen Daggett, Jacqui Daglish, Sandeep Dahiya, Anne Dale, Katie Dale, Michaela Dale, Sam Dale, Jolyon Dales, Helen Dalgleish, Helen Dallow, Dermot Dalton, Zoe Daly, Eleanor Damm, Akila Danga, Amelia Daniel, Priya Daniel, Allison Daniels, Adela Dann, Sandra Danso-Bamfo, Alex Darbyshire, Janet Darbyshire, Paul Dargan, Paul Dark, Kate Darlington, Sarah Darnell, Tom Darton, Guledew Darylile, Manjusha Das, Sukamal Das, Martin Daschel, Joanne Dasgin, Dibyendu Datta, Anna Daunt, Vaishali Dave, Emily Davenport, Mark Davey, Miriam Davey, Molly Davey, Mini David, Alexander Davidson, Laura Davidson, Neil Davidson, Richard Davidson, Albert Davies, Amanda Davies, Amy Davies, Angela Davies, Carolyn Davies, Catrin Davies, Drew Davies, Elaine Davies, Ffyon Davies, Helen Davies, Jim Davies, Karen Davies, Kelly Davies, Kim Davies, Louisa Davies, Matthew Davies, Michelle Davies, Nina Davies, Owen Davies, Patrick Davies, Rachel Davies, Rhys Davies, Ruth Davies, Sarah Davies, Simon Davies, Alison Davis, Gwyneth Davis, Illinos Davis, Julie-Ann Davis, Katherine Davis, Peter Davis, Alexander Davison, Christine Dawe, H Dawe, Mark Dawkins, Danielle Dawson, Elizabeth Dawson, Joy Dawson, Susan Dawson, Tom Dawson, Andrew Daxter, Andrew Day, Jacob Day, Jeremy N Day, Jamie D'Costa, Parijat De, Duneesha de Fonseka, Toni de Freitas, Frederico De Santana Miranda, Eleanor de Sausmarez, Shanika de Silva, Thushan de Silva, Jessica De Sousa, Paulo De Sousa, James de Souza, Anthony De Soyza, Natasha de Vere, Johannes de Vos, Bethan Deacon, Sharon Dealing, Anna Dean, Julie Dean, Katrina Dean, Stephen Dean, Tessa Dean, Jill Deane, James Dear, Effie Dearden, Alison Deary, Catherine Deas, Samuel Debbie, Gabor Debreceni, Vashist Deelchand, Matthew Deeley, Joanne Deery, Emmanuel Defever, Manuela Del Forno, Arnold Dela Rosa, Amanda Dell, Carrie Demetriou, David DeMets, Jane Democratis, Jacqueline Denham, Emmanuelle Denis, Laura Denley, Craig Denmade, Kathy Dent, Martin Dent, Elise Denton, Tom Denwood, Nishigandh Deole, Darshita Depala, Maria Depante, Susan Dermody, Amisha Desai, Asmita Desai, Purav Desai, Sanjeev Deshpande, Vai Deshpande, Sirjana Devkota, Usha Devkota, Prakash Dey, Vishal Dey, Rogin Deylami, Kevin Dhaliwal, Sundip Dhani, Amandeep Dhanoa, Mili Dhar, Devesh Dhasmana, Ekanjali Dhillon, Reiss Dhillon, Meghnath Dhimal, Priya Dias, Stephanie Diaz, Kayleigh Diaz-Pratt, Debbie Dickerson, Pamela Dicks, Stuart Dickson, J Digby, Sean Dillane, Sarah Diment, Paul Dimitri, Thai Ha Dinh, Alex Dipper, Laura Dirmantaite, Lisa Ditchfield, Sarah Diver, Lavanya Diwakar, Caroline Dixon, Giles Dixon, Brice Djeugam, Petr Dlouhy, Andrea D'Mello, Paul Dmitri, Laurence Dobbie, Marinela Dobranszky Oroian, Charlotte Dobson, Lee Dobson, Marie Docherty, David Dockrell, James Dodd, Jackie Dodds, Rebecca Dodds, Steve Dodds, Richi Dogra, Erin Doherty, Warren Doherty, Yumiko Doi, Iain Doig, Eleanor Doke, Daniel Dolan, Mark Dolman, Rozzie Dolman, Lisa Donald, Callum Donaldson, Christopher Donaldson, Denise Donaldson, Gillian Donaldson, Kate Donaldson, Joanne Donnachie, Eilish Donnelly, Ronan Donnelly, Aravindhan Donohoe, Gemma Donohoe, Bryan Donohue, Sinead Donton, Emma Dooks, Grainne Doran, Kane Dorey, Sharon Dorgan, Moonira Dosani, Davinder Dosanjh, Paula Dospinescu, Katie Douglas, Jonathan Douse, Lucy Dowden, Michelle Dower, Sud Dowling, Nicola Downer, Charlotte Downes, Rob Downes, Thomas Downes, Damian Downey, Robert Downey, Louise Downs, Simon Dowson, Cornel Dragan, Cristina Dragos, Maire Drain, Chelsea Drake, Victoria Drew, Olivia Drewett, Celine Driscoll, Helena Drogan, Graham Drummond, Katie Drury, Ronald Druyeh, Jack Dryburgh-Jones, Simon Drysdale, An Du Thinh, Hazel Dube, Judith Dube, Stephen Duberley, Hayley Duckles-Leech, Nicola Duff, Emma Duffield, Helen Duffy, Lionel Dufour, Annette Duggan, Parveen Dugh, Janice Duignan, Simon Dummer, Andrew Duncan, Christopher Duncan, Fullerton Duncan, Gregory Duncan, 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Linda Folkes, Daniela M Font, Aiwyne Foo, Jane Foo, Andrew Foot, Jayne Foot, Jane Forbes, Jamie Ford, Jennifer Foreman, Caroline Fornolles, Adam Forrest, Ellie Forsey, Miranda Forsey, Thomas Forshall, Elliot Forster, Julian Forton, Emily Foster, Joseph Foster, Rachel A Foster, Tracy Foster, Angela Foulds, Ian Foulds, Folakemi Fowe, Emily Fowler, Robert Fowler, Stephen Fowler, Claire Fox, Heather Fox, Jonathan Fox, Lauren Fox, Natalie Fox, Olivia Fox, Simon Fox, Sarah-Jane Foxton, Rebecca Frake, Alex Francioni, Olesya Francis, Rebecca Francis, Sarah Francis, Sasha Francis, Theodora Francis-Bacon, Helen Frankland, Jessica Franklin, Catherine Fraser, Sharon Frayling, Martyn Fredlund, Carol Freeman, Elaine Freeman, Hannah Freeman, Nicola Freeman, Clare Freer, Eleanor French, Matthew Frise, Renate Fromson, Adam Frosh, John Frost, Victoria Frost, Oliver Froud, Rachel Frowd, Arun Fryatt, Bridget Fuller, Liz Fuller, Tracy Fuller, Duncan Fullerton, Carrie Fung, Gayle Fung, Sarah Funnell, John 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Matthew Graham-Brown, Julia Grahamslaw, Gianluca Grana, Tracyanne Grandison, Louis Grandjean, Alison Grant, Ann Grant, David Grant, Matthew Grant, Pauleen Grant, Rhys Gravell, Jenny Graves, Alasdair Gray, Catherine Gray, Georgina Gray, Jackie Gray, Karen Gray, Nicola Gray, Sebastian Gray, Alan Grayson, Fiona Greaves, Paul Greaves, Alastair Green, Charlotte Green, Christopher A Green, David Green, Frederick Green, Joel Green, Marie Green, Nicola Green, Stacey Green, Diarra Greene, Philippa Greenfield, Alan Greenhalgh, Daniel Greenwood, Sandra Greer, James Gregory, Jane Gregory, Katie Gregory, Tamsin Gregory, Jill Greig, Julia Greig, Rebecca Grenfell, Teena Grenier, Susan Grevatt, Glaxy Grey, Andrew Gribbin, Amy Gribble, Natasha Grieg, Douglas Grieve, Ben Griffin, Denise Griffin, Mel Griffin, Sian Griffith, Andrew Griffiths, Daniel Griffiths, David Griffiths, Donna Griffiths, Isabel Griffiths, Mark Griffiths, Nicola Griffiths, Oliver Griffiths, Sarah Griffiths, Yvonne Griffiths, Sofia 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William Halford, Alistair Hall, Anthony Hall, Claire Hall, Elizabeth Hall, Fiona Hall, Helen Hall, Jennifer Hall, Kathryn Hall, Jan Hallas, Kyle Hallas, Charles Hallett, Heather Halls, Maryam Hamdollah-Zadeh, Bilal Hameed, Raph Hamers, Imran Hamid, Mohamad Hamie, Bethany Hamilton, Fergus Hamilton, Leigh Hamilton, Nicola Hamilton, Sara Hamilton, Ruth Hamlin, Eleanor Hamlyn, Beatrice Hammans, Shirley Hammersley, Kate Hammerton, Bev Hammond, Leah Hammond, Fiona Hammonds, Ibrahim Hamoodi, Karen Hampshire, Jude Hampson, Lucy Hampson, Ozan Hanci, Sadiyah Hand, Jasmine Handford, Soran Handrean, Sarah Haney, Sheharyar Hanif, E Hanison, Esther Hanison, Jennifer Hannah, Amy Hannington, Merhej Hannun, Aidan Hanrath, Anita Hanson, Jane Hanson, Kathryn Hanson, Steve Hanson, Mazhar Ul Haq, Ala Haqiqi, Monjurul Haque, Lesley Harden, Zoe Harding, Simon Hardman, Joanna Hardy, Kumar Haresh, Rachel Harford, Beverley Hargadon, Carolyn Hargreaves, James Hargreaves, Alice Harin, Mohammed Haris, Edward 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Val Irvine, Robert Irving, Mina Ishak, Erica Isherwood, Aminul Islam, Samsul Islam, Abdurrahman Islim, Ali Ismail, Omar Ismail, Caroline Ison, M'hamedi Israa, Sharon Isralls, Monica Ivan, Chineze Ivenso, Ashleigh Ivy, Sophie Iwanikiw, Karen Ixer, Menaka Iyer, Mia Iyer, Calum Jack, Amanda Jackson, Ben Jackson, Beth Jackson, Ella Jackson, Helen Jackson, Lauren Jackson, Melanie Jackson, Nicola Jackson, Shane Jackson, Patricia Jacob, Reni Jacob, Nicola Jacques, Anisa Jafar, Daniel Jafferji, Ali Jaffery, Chandrashekar Jagadish, Vijay Jagannathan, Mandeep Jagpal, Fernandez R Jaime, Neemisha Jain, Seema Jain, Susan Jain, Sanjay Jaiswal, Danyal Jajbhay, Thomas Jaki, Bintou Jallow, Yusuf Jaly, Sabine Jamal, Zeba Jamal, Yasmin Jameel, Albie James, Christie James, Kate James, Lee James, Linda James, Mark James, Nicholas James, Olivia James, Rebecca James, Ruth James, Tracy James, Jack Jameson, Aaron Jamison, Phoebe Jane, Azara Janmohamed, Deepa Japp, Victor Jardim, Catherine Jardine, Emma 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Mark Johnson, Nelsonseelan Johnson, Oliver Johnson, Claire Johnston, Janet Johnston, Susan Johnston, Victoria Johnston, Dawn Johnstone, Ed Johnstone, Janet Johnstone, Manohar Joishy, Adam Jones, Alistair Jones, Annabel Jones, Ben Jones, Bryony Jones, Carys Jones, Ceri Jones, Charlotte Jones, Christine E Jones, Debra Jones, Emily Jones, Gareth Jones, Geraldine Jones, Jac Jones, James Jones, Jonathon Jones, Julie Jones, Kate E Jones, Laura Jones, Laura M Jones, Louise Jones, Mathew Jones, Nicola Jones, Paul Jones, Rhianna Jones, Ruth E Jones, Samantha Jones, Sophie Jones, Stefanie Jones, Steve Jones, Taya Jones, Tim Jones, Tracey Jones, Ramya Jonnalagadda, Rebecca Jordache, Sanal Jose, Anna Joseph, P Aiden Joseph, Rosane Joseph, Sibet Joseph, Dhaara Joshi, Mehul Joshi, Pratichi Joshi, Benz Josiah, Tiffany Joyce, Adriel Ju Wen Kwek, Edward Jude, Parminder Judge, Jessica Juhl, Sirisha Jujjavarapu, Mark Juniper, Edmund Juszczak, Deepthi Jyothish, Kasamu Kabiru Dawa, Mark Kacar, Nikhil 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Martin Kelly, Michael Kelly, Rosalind Kelly, Sinead Kelly, Stephen Kelly, Mary Kelly-Baxter, Marketa Keltos, Timothy Kemp, Alexandra Kendall-Smith, Sarah Kennard, Ann Kennedy, James Kennedy, Sophie Kennedy-Hay, Julia Kenny, Melanie Kent, Lynne Keogan, Alexander Keough, A Kerr, Andrew Kerr, Caroline Kerrison, Anthony Kerry, Helen Kerslake, Ian Kerslake, Helen Kerss, Jocelyn Keshet-Price, Evelyne Kestelyn, Georgina Keyte, Abdul Khadar, Ali Khalid, Muhammad U Khalid, Syed Khalid, Amir Khalil, Asma Khalil, Sijjad Khalil, Abubakar Khan, Ali Khan, Al-Imran Khan, Arham Khan, Asad Khan, Aurangzeb Khan, Burhan Khan, Fatimah Khan, Kausik Khan, Malik A Khan, Marria Khan, Mehrunnisha Khan, Mohammad Khan, Nayeem Khan, Omar Khan, Rahila Khan, Shabana Khan, Shahul Khan, Shoaib Khan, Tasaduksultan Khan, Waseem Khan, Usman F Khatana, Jibran Khatri, Jyoti Khatri, Hafiza Khatun, Taslima Khatun, Mena Kheia, Jacyntha Khera, Htet Htet Ei Khin, Najaf Khoja, Kiran Khokhar, Chloe Khurana, Faith Kibutu, Andrew 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Laura Korcierz, James Korolewicz, George Koshy, Chris Kosmidis, Jalpa Kotecha, Easwari Kothandaraman, Leonidas Koukouflis, Koushan Kouranloo, Rukhsana Kousar, Margarita Kousteni, Maja Kovac, Alex Kozak Eskenazia, Kestutis Krasauskas, Raghu Krishnamurthy, Vinodh Krishnamurthy, Manju Krishnan, Hari Krishnan, Suzanne Krizak, Sean Krupej, Agnieszka Kubisz-Pudelko, Soren Kudsk-Iversen, Aurimas Kudzinskas, Chirag Kukadiya, Nainesha Kulkarni, Aditi Kumar, Mayur Kumar, Ramesh Kumar, Ravi Kumar, Rita Kumar, Rupa Kumar, Satish Kumar, Vimal Kumar, Arun Kundu, Heinke Kunst, Amit Kurani, Mohammed Kurdy, Rincy Kurian, Vimal Kurmars, Cameron Kuronen-Stewart, Ranganai S Kusangaya, Vlad Kushakovsky, Apexa Kuverji, Amma Kyei-Mensah, Thyra Kyere-Diabour, Moe Kyi, Nyan May Kyi, Laura Kyle, Karali-Tsilimpari Kyriaki, Julius Labao, Louise Lacey, Nikki Lack, Emma Ladlow, Heather Lafferty, Shondipon Laha, Sushil Lahane, Clement Lai, James Lai, Robert Laing, Inez Laing-Faiers, Emily Laity, Nicki Lakeman, David Lalloo, Fiona Lalloo, Alison Lam, Fiona Lamb, Lucy Lamb, Thomas Lamb, Pauline Lambert, Claudia Lameirinhas, Mohammed K G Lami, Abigail Lamikanra, Holly Lamont, Michal Lamparski, Djillali Lamrani, Christine Lanaghan, Ivone Lancona-Malcolm, Geraldine Landers, Martin J Landray, Matthew Lane, Nicholas Lane, Alidih Lang, Stephen Lang, Daniel Langer, Margaret Langley, Charles Langoya, Emily Langthorne, Taiya Large, Wojciech Lason, Anna Last, Scott Latham, Victoria Latham, John Latham-Mollart, Afzal Latheef, Nang Latt, Dawn Lau, Eva Lau, Myra Laurenson, Hou Law, Jessica Law, Penny Law, Richard Law, Emma Lawrence, Neil Lawrence, Ryan Lawrie, Louise Lawson, Michael Lay, Christine Laycock, Reina Layug, Maria Lazo, Vietland Le, Amelia Lea, William Lea, Ian Leadbitter, Thomas Leahy, Richard Lean, Lorna Leandro, Darren Leaning, Sandra Leason, Marie A Ledingham, Emma Lee, Hannah Lee, Irish Lee, Judith Lee, Sam Lee, Shi Han Lee, Simon Lee, Sindy Lee, Stephanie Lee, Tracey Lee, Xiang Lee, Robyn Lee, Diana Lees, Jennifer Lees, Helen Legge, Julian Leggett, Katie Leigh-Ellis, Nicky Leitch, Eleni Lekoudis, Petula Lemessy, Nicholas Lemoine, Katy Leng, Katrina Lennon, Liz Lennon, Kelly Leonard, Wen Leong, Nicky Leopold, Oskar Lepiarczyk, Isla Leslie, Eleni Lester, Ullrich Leuschner, Emma Levell, Chris Levett, Alice Lewin, Alison Lewis, David Lewis, Dee Lewis, Joanne Lewis, Joseph Lewis, Kathryn Lewis, Keir Lewis, Leon Lewis, Marissa Lewis, Rob Lewis, Robert Lewis, Catherine Lewis-Clarke, Adam Lewszuk, Penny Lewthwaite, Samantha Ley, Angela Liao, Victoria Licence, David Lieberman, Susan Liebeschuetz, Nicky Lightfoot, Patrick Lillie, Ben Lim, Carys Lim, Ee Thong Lim, Ivy Lim, Terence Lim, Wei Shen Lim, Wilson Lim, James Limb, Usha Limbu, Christian Linares, Dermot Linden, Gabriella Lindergard, Kate Lindley, Charlotte Lindsay, Emily Lindsay, Max Lindsay, Helen Lindsay- Clarke, Mirella Ling, Claire Lingam, Linette Linkson, Mike Linney, Louise Linsell, Conrad Lippold, George Lipscomb, Karen 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Luintel, H Luke, Jane Luke, Naomi Lungu, Apurva Lunia, Muriel Lunn, Ji Luo, Cindy N Luximon, Barrie Lyell, Elisavet Lyka, Audrey Lynas, Ceri Lynch, Daniel Lynch, Daniella Lynch, Stephen Lynch, Rea-Grace Maamari, Hannah Mabb, Louies Mabelin, Jessica Macaro, Kateryna Macconaill, Chloe Macdonald, Claire Macfadyen, James G Macfarlane, Jill Macfarlane, Laura Macfarlane, Lisa MacInnes, Iain MacIntyre, Jill MacIntyre, Kirsten Mack, Callum Mackay, Euan Mackay, Laura Mackay, Alexander Mackenzie, Matt Mackenzie, Robert MacKenzie Ross, Ami Mackey, Fiona Mackie, Robert Mackie, Carolyn Mackinlay, Claire Mackintosh, Katherine Mackintosh, Mary J MacLeod, Michael Macmahon, Andrew MacNair, Catherine Macphee, Iain Macpherson, Catriona Macrae, Allan MacRaild, Alannah Madden, Mary Madden, Norman Madeja, Pradeep Madhivathanan, Madhavi Madhusudhana, Alpha Madu, Lorraine Madziva, Marion Mafham, Nick Magee, Frederick Magezi, Negar Maghsoodi, Christopher Magier, Marios Magriplis, Natasha Mahabir, Subramanian 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Marcus, Maria Marecka, Gomathi Margabanthu, Jordi Margalef, Lavinia Margarit, Georgios Margaritopoulos, Mike Margarson, Fernandez M Maria del Rocio, Teresa Maria Pfyl, Victor Mariano, Ashleigh Maric, Grace Markham, Maria Marks, P Marks, Elisabeth Marouzet, Arran Marriott, Cheryl Marriott, Nemonie Marriott, Brian Marsden, Christopher Marsden, Karen Marsden, Paul Marsden, Sarah Marsden, Tracy Marsden, Robyn Marsh, Adam Marshall, Andrew Marshall, Gail Marshall, Henry Marshall, Jaimie Marshall, Jenna Marshall, Nicola Marshall, Riley Marshall, Jennifer Marshall, Emmeline Martin, Hayley Martin, Hope Martin, Jane Martin, Karen Martin, Kate Martin, Laila Martin, Michael Martin, Noelia Martin, Tim Martin, Winston Martin, Sarah Martin, Tim Martindale, Marcus Martineau, Lauren Martinez, Jose C Martinez Garrido, Juan Martin-Lazaro, Lucas Martins Ferreira, Vijay K Maruthamuthu, Gemma Maryan, Roman Mary-Genetu, Sam Maryosh, Vidan Masani, Diego Maseda, Sheila Mashate, Yasaman Mashhoudi, Al Mashta, Izhaq Masih, Sanna Masih, Nick Maskell, Perry Maskell, Matthew Masoli, Rebecca Mason, Richard Mason, Ruth Mason, Claire Mason, Mohammad Masood, Mohammad T Masood, Syed S M E Masood, Aaqib Masud, Lear Matapure, Cristina Matei, Ropafadzo Matewe, Manraj Matharu, Stephy Mathen, Alex Mather, Nicole Mather, Jonathan Mathers, Joanna Matheson, Amal Mathew, Anna Mathew, Moncy Mathew, Verghese Mathew, Jesha Mathews, Kate Mathias, Alexander Mathioudakis, Darwin Matila, Wadzanai Matimba-Mupaya, Nashaba Matin, Elina Matisa, Max Matonhodze, Elijah Matovu, Jaysankar Mattappillil, Alison J Matthews, Heather Matthews, Helen Matthews, Fiona Maxton, Adam Maxwell, Veronica Maxwell, James May, Joanne May, Philippa May, Irving Mayanagao, Matthew Maycock, Graham Mayers, Victoria Maynard, Shelley Mayor, Ibreaheim Mazen, Andrea Mazzella, Nyambura Mburu, Eleanor McAleese, Paul McAlinden, Audrey McAlpine, Graeme McAlpine, Jonathan McAndrew, Hamish McAuley, Sarah McAuliffe, Claire McBrearty, Erin McBride, Michael 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Abdelrahman Mohamed, Arez Mohamed, Osab Mohamed, Waheed Mohammad, Aliabdulla Mohammed, Omer Mohammed, Yaser N S Mohammed, Bilal A Mohamud, Amr Moharram, Hoi-Ping Mok, Jonathan Mok, Christine Moller-Christensen, Mateus Mollet, Malid Molloholli, Aoife Molloy, Linda Molloy, Andrew Molyneux, Tasnim Momoniat, Holly Monaghan, Krista Monaghan, Shiva Mongolu, Tesha Monika, Katelyn Monsell, Mahmoud Montasser, Alan Montgomery, Hugh Montgomery, Prebashan Moodley, Margaret Moody, Nick Moody, Angela Moon, James Moon, Ji-Hye Moon, Maria Moon, May Moonan, Parvez Moondi, Alex Moore, Christopher Moore, David A J Moore, Faye Moore, Judith Moore, Laura Moore, Sally Moore, Sonia Moore, Rachel Moores, Ed Morab, Jose Morales, Nuria Moramorell, Louise Moran, Grishma Moray, Jeronimo Moreno-Cuesta, Amy Morgan, Caitlin Morgan, Christine Morgan, Colin Morgan, Lauren Morgan, Leila Morgan, Matthew Morgan, Patrick Morgan, Katie Morgan-Jones, Emily Morgan-Smith, Anna Morley, Thomas Morley, Wendy Morley, Anna Morris, 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Gireesha Naik, Rishi Naik, Samir Naik, Devu S Nair, Rajiv Nair, Tanushree Nair, Jay Naisbitt, Kerry Naismith, Sri Nallapareddy, Soum Nallapeta, Arumugan Nallasivan, Uttam Nanda, Aarti Nandani, Ali Raza Naqvi, Asadullah Naqvi, Sara Naqvi, Sophia Nasa, Dominic Nash, Nader Nasheed, Abdul Nasimudeen, Umer Nasir, Tahir Nasser, Anuja Natarajan, Geetha Natarajan, Nalin Natarajan, Nikhila Natarajan, Rajkumar Natarajan, Noel Nathaniel, Mala Nathvani, Priyan Nathwani, George Nava, Neena Navaneetham, Jeya Navaratnam, Helen Navarra, Sadaf Naveed, John Navin, Khuteja Nawaz, Sarfaraz Nawaz, Shasta Nawaz, Bonilla Nayar, Suzanne Naylor, Moez Nayyar, Farrah Naz, Mobeena Naz, Babak Nazari, S Nazir, Sehar Nazir, Dumisani Ncomanzi, Onyine Ndefo, Alan Neal, Elaine Neary, Mostafa Negmeldin, Paula Neill, Hector E Neils, Avideah Nejad, Louise Nel, Marie Nelson, Richard Nelson, Scott Nelson, Erni Nelwan, Rajesh Nemane, Samiksha Nepal, Daniel Nethercott, Kimberley Netherton, Kimberley Nettleton, Alison Newby, Angela Newby, David Newby, Tracy Newcombe, Diana Newman, Julie Newman, Oscar Newman, Tabitha Newman, Thomas Newman, Rachel Newport, Maria Newton, Anthony Y K C Ng, Ka Wing Ng, Maxine Ng, Sarah Ng, Wee Jin Ng, Thomas Ngan, Gabriel CE Ngui, Alice Ngumo, Caoimhe Nic Fhogartaigh, Nathalie Nicholas, Philip Nicholas, Donna Nicholls, Lisa Nicholls, Alice Nicholson, Anne Nicholson, Annette Nicholson, Ian Nickson, Eileen Nicol, Elizabeth Nicol, Rebecca Nicol, Pantelis Nicola, Antony Nicoll, Pantzaris Nikolaos, Georgii Nikonovich, Annette Nilsson, Kofi Nimako, Louise Nimako, Camus Nimmo, Preethy Ninan, Mahesh Nirmalan, Muhammad Nisar, Toby Nisbett, Aksinya Nisha James, Sabaahat Nishat, Tomoko Nishiyama, Sara Nix, Jennifer Nixon, Maxine Nixon, Khwaja Nizam Ud Din, Maria Nizami, Lyrics Noba, Harriet Noble, Hsu M Noe, Jerry Nolan, Zahid Noor, Zaid Noori, Louis Norman, Rachel Norman, Karen Norris, Lillian Norris, Sally Ann Nortcliffe, Fiona North, Julie North, Thomas North, John Northfield, Samantha 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Kirandip Punia, Saleel Punnilath Abdulsamad, Laura Purandare, Daniel Purchase, Corrina Purdue, Bally Purewal, Molly Pursell, Gregory Purssord, Rory Purves, Sarah Purvis, Khairunnisa Puspatriani, Kathryn Puxty, Zoe Puyrigaud, Michael Pynn, Tariq Qadeer, Mohammad Qayum, Corrine Quah, Sheena Quaid, Nathaniel Quail, Charlotte Quamina, Alice Quayle, Eleanor Quek, Siobhan Quenby, Xinyi Qui, Vanessa Quick, Julie Quigley, Juan-Carlos Quijano-Campos, Andrew Quinn, James Quinn, Tom Quinn, Quratulain Quratulain, Danya Qureshi, Ehsaan Qureshi, Hasanain Qureshi, Khadija Qureshi, Nawaz Qureshi, Qurratulain Qurratulain, Saad Qutab, Muhammad S Rabbani, Simon Rabinowicz, Madalina Raceala, Raissa Rachman, Laura Rad, Jane Radford, Liz Radford, Jayachandran Radhakrishnan, Cecillia Rafique, Jethin Rafique, Muhammad Rafique, Ravi Ragatha, Aiswarya Raghunathan, Abigail Raguro, Shankho D Raha, Sana Rahama, Mutia Rahardjani, Karen Rahilly, Faisal Rahim, Abdul H Rahimi, Haseena R Rahimi, Muhammad Rahman, Salim Ur Rahman, Prajan Rai, Lenka Raisova, Arjun Raj, Pradeep Rajagopalan, Nithy Rajaiah, Kanendran Rajalingam, Arvind Rajasekaran, Aylur Rajasri, Sagar Rajbhandari, Thurkka Rajeswaran, Jyothi Rajeswary, Jeyanthy Rajkanna, Gayathri Rajmohan, Ruth Rallan, Katherine Ralston, Maximilian Ralston, Matsa Ram, Balaji Ramabhadran, Fathima Ramali, Mohamed Ramali, Athimalaipet Ramanan, Shashikira Ramanna, Maheshi Ramasamy, Irfah Rambe, Dhanishta Ramdin, Jozel Ramirez, Mylah Ramirez, Geshwin Ramnarain, Lidia Ramos, Tommy Rampling, Shanthi Ramraj, Alex Ramshaw, Aleem Rana, Ghulam F Rana, Rehman Rana, Abby Rand, James Rand, Harpal Randheva, Poonam Ranga, Manmeet Rangar, Harini Rangarajan, Sameer Ranjan, Hannah Rank, Poormina Ranka, Rajesh Rankhelawon, Anita Rao, Sandhya Rao, Sanjay Rao, Deepak Rao, Althaf A Rasheed, Khalid Rashid, Simbisai Ratcliff, Sam Ratcliffe, Sophy Ratcliffe, Sanjeev Rath, Mohmad I Rather, Selina Rathore, Aravinden Ratnakumar, Jonathan Ratoff, Deepa Rattehalli, Jason Raw, Rachael 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William Ricketts, Hannah Rickman, Anna Riddell, Mohamed Ridha, Carrie Ridley, Paul Ridley, Gudrun Rieck, Linsey Rigby, Samita Rijal, Hannah Riley, Matthew Riley, Phil Riley, Atika Rimainar, Zwesty V P Rimba, Dominic Rimmer, Robert Rintoul, Andrew Riordan, David Ripley, Naomi Rippon, Chloe Rishton, Michael Riste, David Ritchie, Jane Ritchie, Andy Ritchings, Pilar Rivera Ortega, Vanessa Rivers, Batool Rizvi, Syed AS Rizvi, Syed H M Rizvi, James Robb, David J Roberts, Ian Roberts, Jane Roberts, Jean Roberts, Karen Roberts, Mark Roberts, Nicky Roberts, Philip Roberts, Rebecca Roberts, Calum Robertson, James Robertson, Jamie Robertson, Nichola Robertson, Stuart Robertson, Nicole Robin, Caroline Robinson, Emma Robinson, Gisela Robinson, Hannah Robinson, Jemima Robinson, Kate Robinson, Matthew Robinson, Ryan Robinson, Sandra Robinson, Alexandra Robinson, Steve Robson, Lisa Roche, Samantha Roche, Natalie Rodden, Alistair Roddick, Jack Roddy, Marion Roderick, Alison Rodger, Faye Rodger, Megan 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Donna Watterson, Daniel Watts, John Watts, Merlin Watts, Victoria Waugh, Emma Wayman, Akhlaq Wazir, Mark Weatherhead, Nick Weatherly, Hayley Webb, Kathryn Webb, Kylie Webb, Stephen Webb, Cheryl Websdale, Deborah Webster, Ian Webster, Tim Webster, Ling Wee, Rebecca Weerakoon, Thanuja Weerasinghe, Janaka Weeratunga, Maria Weetman, Shuying Wei, Immo Weichert, David M Weinreich, Hugh Welch, James Welch, Leanne Welch, Steven Welch, A Welford, Samantha Weller, Lucy Wellings, Brian Wells, Susan Wellstead, Berni Welsh, Richard Welsh, Ingeborg Welters, Rachael Welton, Lauren Wentworth, Kate Wesseldine, Magdelena West, Raha West, Ruth West, Sophie West, Luke Western, Ruth Westhead, Heather Weston, Alice Westwood, Bill Wetherill, Sharon Wheaver, Helen Wheeler, Ben Whelan, Matthew Whelband, Amanda Whileman, Alison Whitcher, Andrew White, Benjamin White, Christopher White, Duncan White, Hannah White, James White, Jonathan White, Katie White, Marie White, Nick White, Sarah White, Sonia White, Tracey White, Catherine Whitehead, Anne Whitehouse, Claire Whitehouse, Tony Whitehouse, Julia Whiteley, Sophie Whiteley, Gabriel Whitlingum, David Whitmore, Elizabeth Whittaker, Lindsay Whittam, Ashley Whittington, Helen Whittle, Robert Whittle, Eunice Wiafe, Lou Wiblin, Olivia Wickens, John Widdrington, Jason Wieboldt, Hannah Wieringa, Cornelia Wiesender, Laura Wiffen, Andrew Wight, Christopher Wignall, Danielle Wilcock, Emma Wilcock, Louise Wilcox, Laura Wild, Stephen Wild, Michael Wilde, Peter Wilding, Tracey Wildsmith, Joe Wileman, Joy Wiles, Kate Wiles, Elva Wilhelmsen, Thomas Wiliams, Janet Wilkie, David Wilkin, Hannah Wilkins, Joy Wilkins, Suzanne Wilkins, Iain Wilkinson, Lesley Wilkinson, Nicola Wilkinson, Sophia Wilkinson, Susan Wilkinson, Tim Wilkinson, Sylvia Willetts, Aimee Williams, Alexandra Williams, Alison Williams, Angharad Williams, Ava Williams, Carl Williams, Caroline V Williams, Claire Williams, Dewi Williams, Gail Williams, Gemma Williams, Gina Williams, Hannah Williams, James Williams, Jennie Williams, John Williams, Joseph Williams, Karen Williams, Kathryn Williams, Marie Williams, Matthew Williams, Patricia Williams, Penny Williams, Rupert Williams, Samson Williams, Sarah Williams, Sophie Williams, Tamanna Williams, Annie Williamson, Cath Williamson, Catherine Williamson, Dawn Williamson, James D Williamson, Jodie Williamson, Rachel Williamson, Helen Williamson, Elizabeth Willis, Emily Willis, Heather Willis, Herika Willis, Joanna Willis, Louise Wills, Lucy Willsher, Catherine Willshire, Francesca Willson, Alison Wilson, Andrea Wilson, Antoinette Wilson, Billy Wilson, James Wilson, Karen Wilson, Kate Wilson, Lucinda Wilson, Mark Wilson, Toni Wilson, Marlar Win, Tin Tin Win, Wut Yee Win, Lucinda Winckworth, Laura Winder, Piers Winder, Helen Winmill, Simon Winn, Carmen Winpenny, Helen Winslow, Helen Winter, Jonathan Winter, Barbara Winter-Goodwin, Stephen Wisdom, Matthew Wise, Martin Wiselka, Rebecca Wiseman, Sophie Wiseman, Steven Wishart, Eric Witele, Nicholas Withers, Janet Wittes, Donna Wixted, Therese Wodehouse, Will Wolf, Nicola Wolff, Kirsten Wolffsohn, Rebecca Wolf-Roberts, Magda Wolna, Elena Wolodimeroff, Adam Wolstencroft, Alan Wong, Charlotte Wong, Chi-Hung Wong, Chi-Man Wong, Edwin Wong, Jessica Sue Yi Wong, Kit Y Wong, Mei Yin Wong, Nick Wong, Sam Wong, Amanda Wood, Caroline Wood, Dianne Wood, Fiona Wood, Hannah Wood, Jennifer Wood, Joe Wood, Lisa Wood, Louise Wood, Stephen Wood, Tracy Wood, Katharine Woodall, Rebecca Woodfield, Christopher Woodford, Elizabeth Woodford, Jill Woodford, Louise Woodhead, Timothy Woodhead, Philip Woodland, Marc Woodman, Jane Woods, Katherine Woods, Sarah Woods, Zoe Woodward, Megan Woolcock, Gemma Wooldridge, Rebecca Woolf, Chris Woollard, Christopher Woollard, Louisa Woollen, Emma Woolley, Jade Woolley, Daniel Woosey, Dan Wootton, Joanne Wootton, Daniel Worley, Stephy Worton, Jonathan Wraight, Maria Wray, Kim Wren, Lynn Wren, Caroline Wrey Brown, Catherine Wright, Demi Wright, Francesca Wright, Imogen Wright, Lianne Wright, Rachel Wright, Stephanie Wright, Tim Wright, Caroline Wroe, Hannah Wroe, Henry Wu, Peishan Wu, Pensee Wu, Jonathan Wubetu, Fitria Wulandari, Retno Wulandari, Craig Wyatt, Frederick Wyn-Griffiths, Inez Wynter, Bindhu Xavier, Arnold Xhikola, Zhongyang Xia, Huiyuan Xiao, Masseh Yakubi, May Yan, Freda Yang, Yingjia Yang, Michael Yanney, Woei Lin Yap, Nabil Yaqoob, Salima Yasmin, Bryan Yates, David Yates, Edward Yates, Helen Yates, Thomas Yates, Mark Yates, Charlotte Yearwood Martin, Khin Yein, Fiona Yelnoorkar, Peter Yew, Laura Ylquimiche, Laura Ylquimiche Melly, Inez Ynter, H Yong, Jemma Yorke, Jasmine Youens, Abdel Younes Ibrahim, Eoin Young, Gail Young, Louise Young, Asfand Yousafzar, Sajeda Youssouf, Ahmed Yousuf, Chrissie Yu, Bernard Yung, Daniel Yusef, Said Yusef, Intekhab Yusuf, Anna-Sophia Zafar, Silvia Zagalo, Su Zaher, Aqsa Zahoor, Kareem Zaki, Nabhan Zakir, Kasia Zalewska, Ane Zamalloa, Mohsin Zaman, Shakir Zaman, Julie Zamikula, Louise Zammit, Marie Zammit-Mangion, Esther Zebracki, Daniel Zehnder, Lisa Zeidan, Xiaobei Zhao, Dongling Zheng, Doreen Zhu, Madiha Zia, Omar Zibdeh, Rabia Zill-E-Huma, Ei Thankt Zin, Eleanor Zinkin, Vivian Zinyemba, Christos Zipitis, Arkadiusz Zmierczak, Azam Zubir, Naz Zuhra, Rasha Zulaikha, Sabrina Zulfikar, Carol Zullo, Ana Zuriaga-Alvaro, Sheba Zyengi, Apollo - University of Cambridge Repository, Group, RECOVERY Collaborative, University of St Andrews. School of Medicine, and University of St Andrews. Infection and Global Health Division

Subjects
Male, Antiviral agents/adverse effects, Drug therapy, combination, Antibodies, Monoclonal, Humanized, Antibodies, Viral, COVID-19/drug therapy, Antiviral Agents, SARS-CoV-2/immunology, SDG 3 - Good Health and Well-being, General & Internal Medicine, Infusions, intravenous, Humans, QR180 Immunology, Treatment outcome, Infusions, Intravenous, 11 Medical and Health Sciences, Aged, MCC, Medicine(all), Aged, 80 and over, SARS-CoV-2, Antibodies, monoclonal, humanized/adverse effects, COVID-19, General Medicine, 3rd-DAS, Antibodies, viral/blood, COVID-19 Drug Treatment, RECOVERY Collaborative Group, Hospitalization, Treatment Outcome, QR180, Drug Therapy, Combination, Female
Abstract

The RECOVERY trial is supported by grants to the University of Oxford (Oxford, UK) from UK Research and Innovation (UKRI; Medical Research Council) and the National Institute of Health Research (NIHR; MC_PC_19056), the Wellcome Trust (222406/Z/20/Z) through the COVID-19 Therapeutics Accelerator, and by core funding provided by the NIHR Oxford Biomedical Research Centre, the Wellcome Trust, the Bill and Melinda Gates Foundation, the Foreign, Commonwealth and Development Office, Health Data Research UK, the Medical Research Council Population Health Research Unit, the NIHR Health Protection Unit in Emerging and Zoonotic Infections, and NIHR Clinical Trials Unit Support Funding. TJ is supported by a grant from UK Medical Research Council (MC_UU_00002/14) and an NIHR Senior Research Fellowship (NIHR-SRF-2015-08-001). Background : Casirivimab and imdevimab are non-competing monoclonal antibodies that bind to two different sites on the receptor binding domain of the SARS-CoV-2 spike glycoprotein, blocking viral entry into host cells. We aimed to evaluate the efficacy and safety of casirivimab and imdevimab administered in combination in patients admitted to hospital with COVID-19. Methods : RECOVERY is a randomised, controlled, open-label platform trial comparing several possible treatments with usual care in patients admitted to hospital with COVID-19. 127 UK hospitals took part in the evaluation of casirivimab and imdevimab. Eligible participants were any patients aged at least 12 years admitted to hospital with clinically suspected or laboratory-confirmed SARS-CoV-2 infection. Participants were randomly assigned (1:1) to either usual standard of care alone or usual care plus casirivimab 4 g and imdevimab 4 g administered together in a single intravenous infusion. Investigators and data assessors were masked to analyses of the outcome data during the trial. The primary outcome was 28-day all-cause mortality assessed by intention to treat, first only in patients without detectable antibodies to SARS-CoV-2 infection at randomisation (ie, those who were seronegative) and then in the overall population. Safety was assessed in all participants who received casirivimab and imdevimab. The trial is registered with ISRCTN (50189673) and ClinicalTrials.gov (NCT04381936). Findings : Between Sept 18, 2020, and May 22, 2021, 9785 patients enrolled in RECOVERY were eligible for casirivimab and imdevimab, of which 4839 were randomly assigned to casirivimab and imdevimab plus usual care and 4946 to usual care alone. 3153 (32%) of 9785 patients were seronegative, 5272 (54%) were seropositive, and 1360 (14%) had unknown baseline antibody status. 812 (8%) patients were known to have received at least one dose of a SARS-CoV-2 vaccine. In the primary efficacy population of seronegative patients, 396 (24%) of 1633 patients allocated to casirivimab and imdevimab versus 452 (30%) of 1520 patients allocated to usual care died within 28 days (rate ratio [RR] 0·79, 95% CI 0·69-0·91; p=0·0009). In an analysis of all randomly assigned patients (regardless of baseline antibody status), 943 (19%) of 4839 patients allocated to casirivimab and imdevimab versus 1029 (21%) of 4946 patients allocated to usual care died within 28 days (RR 0·94, 95% CI 0·86-1·02; p=0·14). The proportional effect of casirivimab and imdevimab on mortality differed significantly between seropositive and seronegative patients (p value for heterogeneity=0·002). There were no deaths attributed to the treatment, or meaningful between-group differences in the pre-specified safety outcomes of cause-specific mortality, cardiac arrhythmia, thrombosis, or major bleeding events. Serious adverse reactions reported in seven (

Published
2022

12. COVID-19 vaccine coverage in health-care workers in England and effectiveness of BNT162b2 mRNA vaccine against infection (SIREN): a prospective, multicentre, cohort study

Author

Amanda Semper, P Burns, K Gajee, Amoolya Vusirikala, L Moore, S Joyce, Paul Klenerman, R Longfellow, R Matthews, Jacqueline Hewson, L Prentice, Alastair Grant, Edgar Wellington, A Tengbe, S Ambalkar, Alex Soriano, I Karagiannis, A Ashby, C Carr, O Kay, B Larru, Manjula Meda, T Lewis, H Aziz, R Chaudhuri, Ioannis Karagiannis, Martin S. Williams, J Conneely, Tim Planche, A M Moody, A Ho, Ashley Otter, K McLelland-Brooks, N Todd, J Alderton, Matthew T. G. Holden, A Boulos, T DeSilva, A Rajgopal, R Pritchard Jones, J Khawam, SC Bain, V J Hall, S Birch, Sarah Foulkes, MA Chand, CS Brown, P Cowling, K Hollinshead, M Halkes, M Ramsay, Cathy Rowe, Colin S Brown, Mark Joseph, N Slawson, Blanche Oguti, L Hall, J Russell, Ayoub Saei, Linda Partridge, Shahjahan Miah, L Coke, Steven Platt, Angie Lackenby, Victoria Hall, M Sartaj, L Keen, A Saei, T Chin, C Thomas, Louise Robinson, Christopher W Holmes, C Subudhi, M Beekes, R Laugharne, Diane Wycherley, R.J. Shorten, R Temple-Purcell, H Chenoweth, V Maxwell, A Atti, Padmasayee Papineni, J Giles, K. Black, M Booth, Jane Democratis, D McCracken, L Cromey, Peter Kirwan, D Delgado, D Hilton, R Crosby-Nwaobi, Susanna Dunachie, A Roebuck, G Sebbage, S Foulkes, K Tempeton, Edward M. Smith, J Murira, Ajay Chawla, Joanna Ellis, J Lopez-Bernal, S Jose, Nick Andrews, A Charlett, Bjl Burton, I Sinanovic, N Aldridge, Katie Jeffery, Gretchen A Stevens, Y Ellis, J Powell, Shân Davies, Alan Jackson, Jonathan L. Heeney, A Dave, B Oguti, A Swan, EA Sheridan, Sara Bennett, Susan Hopkins, T Donaghy, Sakib Rokadiya, Jasmin Islam, S Akhtar, J Mouland, P Domingos, J Harwood, Christian Gabriel, Christopher J A Duncan, Stephen R. Williams, S Hams, E Cameron, F Westwell, Keith D. James, Meaghan Kall, K Pagget, Justin Pepperell, Robert Tilley, A O'Kelly, S Horne, K Potts, S Gormley, F Sanderson, Sharen Painter, S. Stone, Mariyam Mirfenderesky, Tabitha Mahungu, S Baillon, R Kyffin, S Organ, S Brake, Andre Charlett, S Brand, D Browne, J Ledger, Meera Chand, Madhumita Shrotri, Michael J. Cole, Debra Padgett, M Lee, Martin Wiselka, A M O'Connell, Minal Patel, Katie Munro, L Haahr, T M Byrne, J Gunn, Naomi F. Walker, P Bakker, P Cieciwa, Stephen Winchester, N Chitalia, B Wadams, Michael P. Murphy, P Staves, Ken Agwuh, Cressida Auckland, Sarah Meisner, Ejm Monk, J Howard, C Duff, Susan R. Hopkins, N Andrews, J Elliott, K Braithwaite, AJ Plant, M Howard, Sharon Campbell, A Nissr, Stuart K. Roberts, D Pople, G Maloney, L Mabey, T Bailey, Simon Warren, S Orr, Alex Horsley, J Radmore, Lance Turtle, Helen V. Smith, Badrinathan Chandrasekaran, C Forsyth, R Lear, A Roynon, Claire Price, Ana Atti, Maria Zambon, Stephen R Knight, Jeremy N. Day, Katja Hoschler, Aarti Shah, Chetan Parmar, Rajeka Lazarus, M Lattimore, Julia Stowe, J Aeron-Thomas, J Tomlinson, L Allsop, A Abdelrazik, C Laven, Silvia D'Arcangelo, Z Naheed, A Cochrane, L Price, Emily MacNaughton, K Munro, E King, Chris Jones, S Mcwilliam, G Boyd, Caroline Kerrison, S Hamer, David W Eyre, T Trinick, J Marrs, F Adair, H Coles, Jameel Khawam, S Board, Gordon B. Mills, Mary Ramsay, Nada Ahmed, D Brooking, J Northfield, Jamie Lopez-Bernal, N Kalakonda, D Ironmonger, Shazaad Ahmad, S Taylor, A Watt, J Graves, D Flanagan, Helen Baxendale, R Penn, Louise Berry, D Corrigan, C Favager, M E Green, V Bateman, N Mahabir, J Osbourne, K Gray, Eleri Wilson-Davies, S Pai, I Knox, S Tonge, G Pottinger, M Brazil, Hayley Crawford, K Court, Daniel Harvey, Brendan A I Payne, A Arenas-Pinto, E Hanna, Robin Gopal, Henrietta U. Okafor, Frances L. Game, A Cross, Benjamin J. Stewart, Kevin K. Brown, Timothy M Reynolds, ED Lacey, V Irvine, Julie V. Robotham, A Lloyd, M Aga, D Brennan, C Loughrey, K Shipman, I Del Rosario, Stephen J. Fowler, H Hodgson, K Nimako, Ruth Simmons, Aditi Pai, S Stewart, R Druyeh, Nicholas J. White, A Bexley, E Defever, G Harrison, Trevor J. Barnes, N Wong, Natalie Gillson, S Khanduri, Sarah Wallace, M O'Kane, A Whileman, Arthur Taylor, A Houston, R Sierra, N Elumogo, Ezra Linley, A Higham, J Islam, J Ashcroft, E Underhill, D Camero, Stacey Donaldson, N Gillson, N Osuji, M Z Qazzafi, J Birch, C Sinclair, E Wellington, D Dhasmana, C Pegg, Reuben McGregor, C Norman, Alison Rodger, D Adeboyeku, L E Hughes, H Johnstone, L Gallego, Tim Brooks, Adrian Hawkins, A Selassi, P Swift, P Mercer, A Cowley, A Gibson, P Harrington, A Broadley, P Ridley, S Evans, Ywj Huang, Dunachie, SJ, and Group, SIREN Study

Subjects
medicine.medical_specialty, business.industry, Incidence (epidemiology), Hazard ratio, General Medicine, 030204 cardiovascular system & hematology, Asymptomatic, Vaccination, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Cohort, Medicine, Population study, 030212 general & internal medicine, medicine.symptom, business, Prospective cohort study, Cohort study
Abstract

Summary Background BNT162b2 mRNA and ChAdOx1 nCOV-19 adenoviral vector vaccines have been rapidly rolled out in the UK from December, 2020. We aimed to determine the factors associated with vaccine coverage for both vaccines and documented the vaccine effectiveness of the BNT162b2 mRNA vaccine in a cohort of health-care workers undergoing regular asymptomatic testing. Methods The SIREN study is a prospective cohort study among staff (aged ≥18 years) working in publicly-funded hospitals in the UK. Participants were assigned into either the positive cohort (antibody positive or history of infection [indicated by previous positivity of antibody or PCR tests]) or the negative cohort (antibody negative with no previous positive test) at the beginning of the follow-up period. Baseline risk factors were collected at enrolment, symptom status was collected every 2 weeks, and vaccination status was collected through linkage to the National Immunisations Management System and questionnaires. Participants had fortnightly asymptomatic SARS-CoV-2 PCR testing and monthly antibody testing, and all tests (including symptomatic testing) outside SIREN were captured. Data cutoff for this analysis was Feb 5, 2021. The follow-up period was Dec 7, 2020, to Feb 5, 2021. The primary outcomes were vaccinated participants (binary ever vacinated variable; indicated by at least one vaccine dose recorded by at least one of the two vaccination data sources) for the vaccine coverage analysis and SARS-CoV-2 infection confirmed by a PCR test for the vaccine effectiveness analysis. We did a mixed-effect logistic regression analysis to identify factors associated with vaccine coverage. We used a piecewise exponential hazard mixed-effects model (shared frailty-type model) using a Poisson distribution to calculate hazard ratios to compare time-to-infection in unvaccinated and vaccinated participants and estimate the impact of the BNT162b2 vaccine on all PCR-positive infections (asymptomatic and symptomatic). This study is registered with ISRCTN, number ISRCTN11041050, and is ongoing. Findings 23 324 participants from 104 sites (all in England) met the inclusion criteria for this analysis and were enrolled. Included participants had a median age of 46·1 years (IQR 36·0–54·1) and 19 692 (84%) were female; 8203 (35%) were assigned to the positive cohort at the start of the analysis period, and 15 121 (65%) assigned to the negative cohort. Total follow-up time was 2 calendar months and 1 106 905 person-days (396 318 vaccinated and 710 587 unvaccinated). Vaccine coverage was 89% on Feb 5, 2021, 94% of whom had BNT162b2 vaccine. Significantly lower coverage was associated with previous infection, gender, age, ethnicity, job role, and Index of Multiple Deprivation score. During follow-up, there were 977 new infections in the unvaccinated cohort, an incidence density of 14 infections per 10 000 person-days; the vaccinated cohort had 71 new infections 21 days or more after their first dose (incidence density of eight infections per 10 000 person-days) and nine infections 7 days after the second dose (incidence density four infections per 10 000 person-days). In the unvaccinated cohort, 543 (56%) participants had typical COVID-19 symptoms and 140 (14%) were asymptomatic on or 14 days before their PCR positive test date, compared with 29 (36%) with typical COVID-19 symptoms and 15 (19%) asymptomatic in the vaccinated cohort. A single dose of BNT162b2 vaccine showed vaccine effectiveness of 70% (95% CI 55–85) 21 days after first dose and 85% (74–96) 7 days after two doses in the study population. Interpretation Our findings show that the BNT162b2 vaccine can prevent both symptomatic and asymptomatic infection in working-age adults. This cohort was vaccinated when the dominant variant in circulation was B1.1.7 and shows effectiveness against this variant. Funding Public Health England, UK Department of Health and Social Care, and the National Institute for Health Research.

Published
2021

13. Implementation and extended evaluation of the Euroimmun Anti-SARS-CoV-2 IgG assay and its contribution to the United Kingdom’s COVID-19 public health response

Author

Angela Sweed, Heli Harvala, Nick Andrews, Heather Whitaker, Amanda Semper, Maria Zambon, Ezra Linley, Paul Klenerman, Jacqueline Hewson, Daniel Bailey, Alexander J. Mentzer, Jessica Jones, Julian C. Knight, Ashley Otter, Abbie Bown, Abigail A. Lamikanra, Gayatri Amirthalingam, Donal T. Skelly, Prem Perumal, Matthew Catton, Tim Brooks, Richard Vipond, Cathy Rowe, Stephen Taylor, and Silvia D'Arcangelo

Subjects
medicine.medical_specialty, 2019-20 coronavirus outbreak, Antibody response, Coronavirus disease 2019 (COVID-19), business.industry, Public health, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Emergency medicine, Medicine, Outbreak, Social care, business, Laboratory facility
Abstract

1.AbstractIn March 2020, the Rare and Imported Pathogens Laboratory at Public Health England, Porton Down, was tasked by the Department of Health and Social Care with setting up a national surveillance laboratory facility to study SARS-CoV-2 antibody responses and population-level sero-surveillance in response to the growing SARS-CoV-2 outbreak. In the following 12 months, the laboratory tested more than 160,000 samples, facilitating a wide range of research and informing PHE, DHSC and UK government policy. Here we describe the implementation and use of the Euroimmun anti-SARS-CoV-2 IgG assay and provide an extended evaluation of its performance. We present a markedly improved sensitivity of 91.39% (≥14 days 92.74%, ≥21 days 93.59%) compared to our small-scale early study, and a specificity of 98.56%. In addition, we detail extended characteristics of the Euroimmun assay: intra- and inter-assay precision, correlation to neutralisation and assay linearity.

Published
2021

14. mRNA vaccination in people over 80 years of age induces strong humoral immune responses against SARS-CoV-2 with cross neutralization of P.1 Brazilian variant

Author

Cathy Rowe, Christine Stephens, Emily Chiplin, Christopher Bentley, Katherine Hilyard, Sue Charlton, Naomi Coombes, Gokhan Tut, Bassam Hallis, Gayatri Amirthalingam, Alex G. Richter, Ashley Otter, Rachel Bruton, Elizabeth J Penn, Andrew Makin, Jianmin Zuo, Philip Saunders, Kevin R. Bewley, Stephanie Leung, Helen Parry, Rosie Watts, Sian E Faustini, Paul Moss, Silvia D'Arcangelo, and Kevin E. Brown

Subjects
Male, COVID-19 Vaccines, QH301-705.5, Science, Antibodies, Viral, General Biochemistry, Genetics and Molecular Biology, Neutralization, Serology, Immune system, Humans, Medicine, RNA, Messenger, Biology (General), BNT162 Vaccine, immunosenescence, Aged, 80 and over, Microbiology and Infectious Disease, Immunity, Cellular, General Immunology and Microbiology, biology, SARS-CoV-2, business.industry, General Neuroscience, Vaccination, Age Factors, COVID-19, General Medicine, Immunosenescence, Antibodies, Neutralizing, Immunity, Humoral, Titer, Spike Glycoprotein, Coronavirus, Immunology, Humoral immunity, biology.protein, Female, Antibody, business, Broadly Neutralizing Antibodies, Research Article, Human
Abstract

Age is the major risk factor for mortality after SARS-CoV-2 infection and older people have received priority consideration for COVID-19 vaccination. However, vaccine responses are often suboptimal in this age group and few people over the age of 80 years were included in vaccine registration trials. We determined the serological and cellular response to spike protein in 100 people aged 80–96 years at 2 weeks after the second vaccination with the Pfizer BNT162b2 mRNA vaccine. Antibody responses were seen in every donor with high titers in 98%. Spike-specific cellular immune responses were detectable in only 63% and correlated with humoral response. Previous SARS-CoV-2 infection substantially increased antibody responses after one vaccine and antibody and cellular responses remained 28-fold and 3-fold higher, respectively, after dual vaccination. Post-vaccine sera mediated strong neutralization of live Victoria infection and although neutralization titers were reduced 14-fold against the P.1 variant first discovered in Brazil they remained largely effective. These data demonstrate that the mRNA vaccine platform delivers strong humoral immunity in people up to 96 years of age and retains broad efficacy against the P.1 variant of concern.

Published
2021

15. Author response: mRNA vaccination in people over 80 years of age induces strong humoral immune responses against SARS-CoV-2 with cross neutralization of P.1 Brazilian variant

Author

Helen Parry, Gokhan Tut, Rachel Bruton, Sian Faustini, Christine Stephens, Philip Saunders, Christopher Bentley, Katherine Hilyard, Kevin Brown, Gayatri Amirthalingam, Sue Charlton, Stephanie Leung, Emily Chiplin, Naomi S Coombes, Kevin R Bewley, Elizabeth J Penn, Cathy Rowe, Ashley Otter, Rosie Watts, Silvia D'Arcangelo, Bassam Hallis, Andrew Makin, Alex Richter, Jianmin Zuo, and Paul Moss

Published
2021

16. Impact of COVID-19 vaccination program on seroprevalence in blood donors in England, 2021

Author

Eleanor Clarke, Cathy Rowe, Kevin E. Brown, Suzanne Elgohari, Gayatri Amirthalingam, Sonia Ribeiro, Camille Tsang, Jacqueline Hewson, Colin N J Campbell, Ezra Linley, Tim Brooks, Mary Ramsay, Ashley Otter, Heather Whitaker, Iain Hayden, and Anissa Lakhani

Subjects
0301 basic medicine, Microbiology (medical), medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 030106 microbiology, Population, COVID-19 vaccines, Blood Donors, Surveys, Antibodies, COVID-19 Serological Testing, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Medicine, Seroprevalence, 030212 general & internal medicine, Antibody prevalence, education, Letter to the Editor, Infection only, education.field_of_study, biology, business.industry, SARS-CoV-2, COVID-19, Virology, Vaccination, Infectious Diseases, biology.protein, Antibody, business
Abstract

The COVID-19 vaccination programme commenced in the UK on 8th December 2020 primarily based on age; by 24 February 2021 approximately 93% of the English population aged 70-79 years had received at least 1 dose of either the Pfizer BioNTech or AstraZeneca vaccines. Using a nucleoprotein assay that detects antibodies following natural infection only and a spike assay that detects both infection and vaccine-induced responses, we aim to describe the impact of vaccination on SARS-CoV-2 antibody prevalence in English blood donors.

Published
2021

17. Network for biomarker immunoprofiling for cancer immunotherapy: Cancer Immune Monitoring and Analysis Centers and Cancer Immunologic Data Commons (CIMAC-CIDC)

Author

Minkyung Song, Sean C. Bendall, Melissa D. Bowman, James Lindsay, Diane Marie Del Valle, J. Jack Lee, Cathy Rowe, Gerold Bongers, Jenny Peterson-Klaus, James H. Doroshow, Valerie M. Tatard-Leitman, F. Stephen Hodi, Holden T. Maecker, Chia-Chi Chang, Sacha Gnjatic, David Patton, Srinika Ranasinghe, Ethan Cerami, Lyndsay Harris, Jeffrey S. Abrams, Magdalena Thurin, Stacey J Adam, Ignacio I. Wistuba, Rebecca A. Enos, Helen X. Chen, Margaret M. Mooney, Sylvie Janssens, Robert R. Jenq, Elad Sharon, Howard Streicher, Chantale Bernatchez, Mina Pichavant, Joyce Yu, Stephen M. Hewitt, Catherine J. Wu, Beatriz Sanchez-Espiridion, Xiaole Shirley Liu, Radim Moravec, Ming Tang, and Gheath Alatrash

Subjects
0301 basic medicine, Cancer Research, medicine.medical_specialty, medicine.medical_treatment, MEDLINE, Immune monitoring, Article, 03 medical and health sciences, 0302 clinical medicine, Cancer immunotherapy, Monitoring, Immunologic, Neoplasms, medicine, Biomarkers, Tumor, Humans, Medical physics, business.industry, Cancer, Immunotherapy, medicine.disease, Clinical trial, 030104 developmental biology, Oncology, Informatics, Biomarker (medicine), business, 030217 neurology & neurosurgery
Abstract

Purpose: Immunoprofiling to identify biomarkers and integration with clinical trial outcomes are critical to improving immunotherapy approaches for patients with cancer. However, the translational potential of individual studies is often limited by small sample size of trials and the complexity of immuno-oncology biomarkers. Variability in assay performance further limits comparison and interpretation of data across studies and laboratories. Experimental Design: To enable a systematic approach to biomarker identification and correlation with clinical outcome across trials, the Cancer Immune Monitoring and Analysis Centers and Cancer Immunologic Data Commons (CIMAC-CIDC) Network was established through support of the Cancer MoonshotSM Initiative of the National Cancer Institute (NCI) and the Partnership for Accelerating Cancer Therapies (PACT) with industry partners via the Foundation for the NIH. Results: The CIMAC-CIDC Network is composed of four academic centers with multidisciplinary expertise in cancer immunotherapy that perform validated and harmonized assays for immunoprofiling and conduct correlative analyses. A data coordinating center (CIDC) provides the computational expertise and informatics platforms for the storage, integration, and analysis of biomarker and clinical data. Conclusions: This overview highlights strategies for assay harmonization to enable cross-trial and cross-site data analysis and describes key elements for establishing a network to enhance immuno-oncology biomarker development. These include an operational infrastructure, validation and harmonization of core immunoprofiling assays, platforms for data ingestion and integration, and access to specimens from clinical trials. Published in the same volume are reports of harmonization for core analyses: whole-exome sequencing, RNA sequencing, cytometry by time of flight, and IHC/immunofluorescence.

Published
2021

18. BNT162b2 Vaccination in People Over 80 Years of Age Induces Strong Humoral Immune Responses with Cross Neutralisation of P.1 Brazilian Variant

Author

Helen Marie Parry, Gokhan Tut, Sian Faustini, Christine Stephens, Philip Saunders, Christopher Bentley, Katherine Hilyard, Kevin Brown, Gayatri Amirthalingam, Sue Charlton, Stephanie Leung, Emily Chiplin, Naomi S. Coombes, Kevin R. Bewley, Elizabeth J. Penn, Cathy Rowe, Ashley Otter, Rosie Watts, Silvia D’Arcangelo, Bassam Hallis, Andrew Makin, Alex G. Richter, Jianmin Zuo, and Paul Moss

Published
2021

19. Performance characteristics of five immunoassays for SARS-CoV-2: a head-to-head benchmark comparison

Author

Andrew J Kwok, Eleanor Barnes, R Levin, Derrick W. Crook, D Crawford-Jones, Y Peng, E Perez, Marta Oliveira, Peto Tea., Nicole Stoesser, S Camara, K K Chau, Monique Andersson, Sally Beer, Matthew Catton, Y Warren, M Borak, L Blackwell, Tim James, Anita Justice, Abbie Bown, A Espinosa, Ashley Otter, Alex J. Richardson, M Emmenegger, Katie Jeffery, W Dejnirattsai, M Fernandez Mendoza, Julian C. Knight, A Linder, L Koukouflis, T Lockett, Rutger J. Ploeg, Tao Dong, Alison Howarth, J K Baillie, H P Tsang, Daniel Ebner, Gillian Rodger, L Silva-Reyes, Sarah Hoosdally, Timothy M Walker, Richard Vipond, S Fassih, Silvia D'Arcangelo, Alex Sienkiewicz, C Wilson, Aimee R. Taylor, Nicola A. Burgess-Brown, Sarah Oakley, Bassam Hallis, Alexander J. Mentzer, Tim Brooks, Cathy Rowe, L Martins Ferreira, Conor Feehily, Thomas G Ritter, S Marinou, N Gent, George Doherty, S Dimitriadis, Juthathip Mongkolsapaya, D Fox McKee, Christopher J. Groves, F Karpe, Kate E. Dingle, Prem Perumal, U Leuschner, Teresa L Street, P M Hammond, Carrow I. Wells, David W Eyre, James Kavanagh, Brian D. Marsden, Richard J. Cornall, Donal T. Skelly, J Pascoe, A Sobrino Diaz, Elizabeth A. Clutterbuck, V Gallardo Sanchez, Justine K. Rudkin, L Mason, R K Young, Susanna Dunachie, T Fordwoh, D S Kim, Dequaire Jmm., Mukhopadhyay Smm., B Horsington, Devender Roberts, E Y Jones, Kathryn Auckland, K Withycombe, Jennifer Hill, H Pickford, Christina Dold, Sheila F Lumley, Angela Sweed, Heli Harvala, A Beveridge, Rory Fairhead, K Paddon, Sadia Bibi, John Frater, Lisa Stockdale, J Morrow, David I. Stuart, Matt J. Neville, M K Verheul, T H Foord, Stuart Cox, Alejandra Fernández-Cid, Christine S. Rollier, L Stafford, Andrew J. Pollard, Susan Wareing, R Kirton, Jesse Coker, Malcolm G Semple, Paul Klenerman, A Mobbs, Thomas Christott, H Thraves, D Georgiou, Gavin R. Screaton, S Felle, José William Martínez, Philippa C Matthews, Stephanie B Hatch, and Mark A. Ainsworth

Subjects
0301 basic medicine, medicine.medical_specialty, medicine.diagnostic_test, Receiver operating characteristic, Head to head, business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Assay sensitivity, Articles, Serology, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Infectious Diseases, Immunoassay, Internal medicine, medicine, 030212 general & internal medicine, Symptom onset, business
Abstract

Summary Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic in 2020. Testing is crucial for mitigating public health and economic effects. Serology is considered key to population-level surveillance and potentially individual-level risk assessment. However, immunoassay performance has not been compared on large, identical sample sets. We aimed to investigate the performance of four high-throughput commercial SARS-CoV-2 antibody immunoassays and a novel 384-well ELISA. Methods We did a head-to-head assessment of SARS-CoV-2 IgG assay (Abbott, Chicago, IL, USA), LIAISON SARS-CoV-2 S1/S2 IgG assay (DiaSorin, Saluggia, Italy), Elecsys Anti-SARS-CoV-2 assay (Roche, Basel, Switzerland), SARS-CoV-2 Total assay (Siemens, Munich, Germany), and a novel 384-well ELISA (the Oxford immunoassay). We derived sensitivity and specificity from 976 pre-pandemic blood samples (collected between Sept 4, 2014, and Oct 4, 2016) and 536 blood samples from patients with laboratory-confirmed SARS-CoV-2 infection, collected at least 20 days post symptom onset (collected between Feb 1, 2020, and May 31, 2020). Receiver operating characteristic (ROC) curves were used to assess assay thresholds. Findings At the manufacturers' thresholds, for the Abbott assay sensitivity was 92·7% (95% CI 90·2–94·8) and specificity was 99·9% (99·4–100%); for the DiaSorin assay sensitivity was 96·2% (94·2–97·7) and specificity was 98·9% (98·0–99·4); for the Oxford immunoassay sensitivity was 99·1% (97·8–99·7) and specificity was 99·0% (98·1–99·5); for the Roche assay sensitivity was 97·2% (95·4–98·4) and specificity was 99·8% (99·3–100); and for the Siemens assay sensitivity was 98·1% (96·6–99·1) and specificity was 99·9% (99·4–100%). All assays achieved a sensitivity of at least 98% with thresholds optimised to achieve a specificity of at least 98% on samples taken 30 days or more post symptom onset. Interpretation Four commercial, widely available assays and a scalable 384-well ELISA can be used for SARS-CoV-2 serological testing to achieve sensitivity and specificity of at least 98%. The Siemens assay and Oxford immunoassay achieved these metrics without further optimisation. This benchmark study in immunoassay assessment should enable refinements of testing strategies and the best use of serological testing resource to benefit individuals and population health. Funding Public Health England and UK National Institute for Health Research.

Published
2020
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20. COVID-19: Rapid antigen detection for SARS-CoV-2 by lateral flow assay: A national systematic evaluation of sensitivity and specificity for mass-testing

Author

Siobhan Campbell, Susan Hopkins, Richard Sedgewick, Kelly Hollier, Wendy Byrne, Ashley Pegg, Scott Nicol, Kimerbley Webster, Suzannah Pegler, Lottie Rawden, Gillian Rodger, Beverley Buck, Richard Clarke, Tom G. Ritter, Sally Hammond, Derrick W. Crook, Sulaksan Panchalingam, Deborah Wright, Victoria Hardy, Kathryn J Saunders, Matthew Catton, Sarah Mckee, Mark Pinkerton, Gloria Calderon, Joanne Waldron, Andrew Harris, Rishab Balaji, Dominic Affron, Penny Carter, Bea Choi, Ian Wickens, Chris D. Turnbull, Elena Hazell, Silvia D'Arcangelo, Tillie Graham, Alex Sienkiewicz, Louise Oliver, Arabella Legard, Freddie Mellor, Rima Colston, Geeta Ghadiali, Ella Baldwin, Stephen W. Wilson, Tim Brooks, Kate Webberley, T Peto, Pam Devall, Jenny Wang, Daniel P. Carter, Elena Turek, Shaolin Chidavaenzi, Gemma Nanson, Kate Allen, James Connolly, Mary-Anne Darby, Caroline Coulson, May Havinden-Williams, Emma Marshall, Mark Driver, Pauline Brown, Beinn Khulusi, Iman Aurfan, Codie Fahey, Zoe Lampshire, Emily A. Protheroe, Antoinette McNulty, Alison Vaughan, T Lockett, Sally-Anne Hurford, Juan Dobaldo Pavon, Rangeni Zinyama, John I. Bell, Toi Neibler, Heena Mistry, Helen Permain, Lorraine Archer, Neil McLeod, Amelia Sterry, Susan Johnston, Alexander Grassam-Rowe, Ruth Johns, Sian Tiley, Olivia Carr, Carly Tibbins, Arro Peace, Christopher H. Logue, Narindar Ghuman, Ellena Badenoch, Carla Bratten, Ashley Price, Patrick Robinson, Sophie Barraclough, Bertie Rowell, Marie Corcoran, Mollie French, Daniel Myers, Emily Eaton, Sophie Moore, Anna Sherkat, Julie Miller, Susan Ridge, Hellen Purnell, Tanzina Chaudary, Juliet Jones, Laura Seeney, Jim Chadwick, Julie Timmins, Sarah Hoosdally, Des Markham, John Vertannes, Sami Tatar, Richard Vipond, Lennard Y. W. Lee, Sara Read, Anita Agasu, Rosaline de Koning, Tegan Gumsley-Read, Ben Holloway, Thomas Knight, Cathy Rowe, Beth Hanney, Herika Willis, Shelha Siddiqui, Aleksander Stawiarski, Kevin K Chau, Ellie Watson, Simon Clark, Babak Afrough, Cara Tomas-Smith, Margaret Broughton-Smith, James O. Robinson, Joy Edwards, Ranoromanana Evans, Thomas Starkey, Anna Gronert, Graham Ellis, Lavanya Sinha, Jane Willcocks, Miriam Avery, Collette Allen, Natasha Ashbridge, Jane Mitchell, Natalie Draper, Anuradha Krishna, Kate Trigg-Hogarth, Bindhu Xavier, Joe Stevens, Leon Peto, Anila Sukumaran, Joseph Gernon, Emma Stanton, Alice Field, Rachel Evans, Vindhya Maripuri, Iftikhar Khan, Justin Liu, Jewel Jones Nwanaforo, Samatha Chilcott, Eloïse Cook, Sharon Kempson, Tom Foord, Lucy Hughes, Vanessa Lucas, Ben Corley, Chris Bridgeman, Grace Westland, David W Eyre, Sally Gordon, Peter Hammond, Kayleigh Collins, Priya Bagga, Gurvinder Gill, Claire Hall, Philippa C Matthews, Dominic Britton, Pauline Derbyshire, Jasmine Gan, Steve Hurdowar, Lloyd Shail, Harry Nuttall, Sheila F Lumley, Becky Evans, Mika Erik Moeser, Dimitris Papoulidis, Lucy Sheppard, Zarina Mirza, Rachel Michel, David Chapman, Kate Ellis, Bassam Hallis, Hannah Fuchs, Jodie Owen, Dawn Clarke, Joanne Henry, Sue Elwell, Rosie Boulton, Vanessa Fenech, Laura Costello, Alison Allanson, Mike Newbury, Prem Perumal, Mary Walters, Angela Bloss, Kate Gilmour, Charles Reynard, Mark A. Ainsworth, Jennifer Smith, Philip Walker, Tim E. A. Peto, Amanda Selassie, Lisa Zeidan, Jane Shallcross, Oliver Topping, Linda Wagstaff, Liam J Peck, Ella Smith, Karen Pearson, Thanh Pham, John Davis, Elizabeth Truelove, Kerry Gibbons, David Tyrrell, David Green, Wendy Osbourne, Anika Goel, Harriet Jackson, Michelle Platton, Daniel Lasserson, Barbara Wilson, Susan Bird, Mark Dolman, Tracy Benford, Joanne Jackman, Marion Evans, Nicole Stoesser, Jackie Sears, Alex Mighiu, Elaine Butcher, Ashley Otter, Akhila Muthuswamy, Tom Fowler, Janet Field, Angela Sweed, Katie Keating-Fedders, Megan Cathrall, Richard Body, Abbie Bown, Gabriella Harker, Richard Clayton, Kim Hicklin, Ant Crook, Sarah Sampson, Sarah Dyas, Cristina Leggio, Hannah Claasen, Rachel Sayers, Louise Woodhead, Carol Beane, Fiona Yelnoorkar, Jake Osbourne, Marina Bishop, Tinashe Kanyowa, Hema Thomas, Ruth Elderfield, H Pickford, Alexandra Rowlands, Patrick Lahert, Kirsten Lee, Ann Sarah Walker, Mark Stockbridge, and Deborah F. McKee

Subjects
VIral antigen detection, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), LFD, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Testing, Population, National evaluation, 01 natural sciences, 03 medical and health sciences, 0302 clinical medicine, Antigen, Lateralflow devices, Lateral flow tests, Medicine, Sampling (medicine), 030212 general & internal medicine, 0101 mathematics, education, Lateral flow, Public health, education.field_of_study, SARS-CoV-2, business.industry, 010102 general mathematics, COVID-19, General Medicine, Coronavirus, United kingdom, Cohort, Emergency medicine, False positive rate, business, Research Paper
Abstract

Background Lateral flow device (LFD) viral antigen immunoassays have been developed around the world as diagnostic tests for SARS-CoV-2 infection. They have been proposed to deliver an infrastructure-light, cost-economical solution giving results within half an hour. Methods LFDs were initially reviewed by a Department of Health and Social Care team, part of the UK government, from which 64 were selected for further evaluation from 1st August to 15th December 2020. Standardised laboratory evaluations, and for those that met the published criteria, field testing in the Falcon-C19 research study and UK pilots were performed (UK COVID-19 testing centres, hospital, schools, armed forces). Findings 4/64 LFDs so far have desirable performance characteristics (orient Gene, Deepblue, Abbott and Innova SARS-CoV-2 Antigen Rapid Qualitative Test). All these LFDs have a viral antigen detection of >90% at 100,000 RNA copies/ml. 8951 Innova LFD tests were performed with a kit failure rate of 5.6% (502/8951, 95% CI: 5.1–6.1), false positive rate of 0.32% (22/6954, 95% CI: 0.20–0.48). Viral antigen detection/sensitivity across the sampling cohort when performed by laboratory scientists was 78.8% (156/198, 95% CI 72.4–84.3). Interpretation Our results suggest LFDs have promising performance characteristics for mass population testing and can be used to identify infectious positive individuals. The Innova LFD shows good viral antigen detection/sensitivity with excellent specificity, although kit failure rates and the impact of training are potential issues. These results support the expanded evaluation of LFDs, and assessment of greater access to testing on COVID-19 transmission. Funding Department of Health and Social Care. University of Oxford. Public Health England Porton Down, Manchester University NHS Foundation Trust, National Institute of Health Research.

Published
2021

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