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

Author

Helen Ratcliffe, Karen S. Tiley, Stephanie Longet, Claire Tonry, Cathal Roarty, Chris Watson, Gayatri Amirthalingam, Iason Vichos, Ella Morey, Naomi L. Douglas, Spyridoula Marinou, Emma Plested, Parvinder K. Aley, Eva Galiza, Saul N. Faust, Stephen Hughes, Clare Murray, Marion R. Roderick, Fiona Shackley, Sam Oddie, Tim W.R. Lee, David P.J. Turner, Mala Raman, Stephen Owens, Paul J. Turner, Helen Cockerill, Jamie Lopez Bernal, Samreen Ijaz, John Poh, Justin Shute, Ezra Linley, Ray Borrow, Katja Hoschler, Kevin E. Brown, Miles W. Carroll, Paul Klenerman, Susanna J. Dunachie, Mary Ramsay, Merryn Voysey, Thomas Waterfield, and Matthew D. Snape

Subjects
Health sciences, Medicine, Medical specialty, Immunology, Virology, Science
Abstract

Summary: SARS-CoV-2 infections in children are generally asymptomatic or mild and rarely progress to severe disease and hospitalization. Why this is so remains unclear. Here we explore the potential for protection due to pre-existing cross-reactive seasonal coronavirus antibodies and compare the rate of antibody decline for nucleocapsid and spike protein in serum and oral fluid against SARS-CoV-2 within the pediatric population. No differences in seasonal coronaviruses antibody concentrations were found at baseline between cases and controls, suggesting no protective effect from pre-existing immunity against seasonal coronaviruses. Antibodies against seasonal betacoronaviruses were boosted in response to SARS-CoV-2 infection. In serum, anti-nucleocapsid antibodies fell below the threshold of positivity more quickly than anti-spike protein antibodies. These findings add to our understanding of protection against infection with SARS-CoV-2 within the pediatric population, which is important when considering pediatric SARS-CoV-2 immunization policies.

Published
2023
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2. Optimising the timing of whooping cough immunisation in mums (OpTIMUM) through investigating pertussis vaccination in pregnancy: an open-label, equivalence, randomised controlled trial

Author

Anna Calvert, Gayatri Amirthalingam, Nick Andrews, Sneha Basude, Matthew Coleman, Hannah Cuthbertson, Anna England, Vanessa Greening, Bassam Hallis, Edward Johnstone, Christine E Jones, Konstantinos Karampatsas, Asma Khalil, Kirsty Le Doare, Mary Matheson, Elisabeth Peregrine, Matthew D Snape, Manu Vatish, Paul T Heath, Agnieszka Burtt, Wendy Byrne, Angelika Capp, Lotoyah Carty, Krina Chawla, Sarah Collins, Emily Cornish, Olwenn Daniel, Jessica Fretwell, Andrew Gorringe, Teresa Gubbins, Tom Hall, Susan Johnston, Uzma Khan, Suzy Lim, Nicki Martin, Ella Morey, Jude Mossop, Katie O'Brien, Nelly Owino, Deborah Powell, Laxmee Ramkhelawon, Helen Ratcliffe, Hannah Roberts, Fenella Roseman, Laura Sparks, Lorraine Stapley, Stephen Taylor, Fiona Walbridge, Rosie Watts, Susan J. Wellstead, and Tabitha Wishlade

Subjects
Microbiology (medical), Infectious Diseases, Virology, Microbiology
Abstract

Background: pertussis vaccination in pregnancy is recommended in many countries to provide protection to young infants. The best timing for this vaccination is uncertain. In the UK, vaccination is recommended between 16 weeks and 32 weeks of gestation. In this trial we aimed to investigate the equivalence of three time periods for pertussis vaccination in pregnancy.Methods: in this open-label, equivalence, randomised controlled trial to investigate equivalence of different time windows for pertussis vaccination in pregnancy, participants were randomly assigned (1:1:1 ratio) to receive a pertussis-containing vaccine (Boostrix-inactivated poliovirus vaccine) in one of three gestational age groups, comprising group 1 (≤23 weeks + 6 days), group 2 (24-27 weeks + 6 days), and group 3 (28-31 weeks + 6 days) using a computer-generated randomisation list. The primary outcome was concentration of pertussis-specific antibodies in the infant born at term at birth. Maternal blood sampling was done before and 2 weeks after vaccination and at delivery, together with a cord sample, and an infant sample was collected at least 4 weeks after primary vaccination. Reactogenicity was assessed for 7 days after vaccination. This trial was registered with ClinicalTrials.gov (NCT03908164).Findings: between May 7, 2019, and Feb 13, 2020, of 1010 women assessed for eligibility, 364 women were recruited and 351 received the intervention (120 in group 1, 119 in group 2, and 112 in group 3). Equivalence of time periods was demonstrated for anti-pertussis toxin and anti-pertactin IgG concentrations. The cord blood geometric mean concentrations of anti-filamentous haemagglutinin IgG were higher with increasing gestational age at vaccination, such that for infants in group 1 (≤23 weeks + 6 days), equivalence to group 3 (28-31 weeks + 6 days) was not shown. Reported rates of fever were similar between study groups.Interpretation: pertussis vaccination at three different time intervals in pregnancy resulted in equivalent concentrations of IgG antibodies in infants against two of the three pertussis antigens assessed. Overall, these findings support recommendations to vaccinate any time between 16 weeks and 32 weeks of gestation.Funding: the Thrasher Research Fund and the National Immunisation Schedule Evaluation Consortium through the National Institute for Health and Care Research policy research programme.

Published
2023
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3. Nasopharyngeal Carriage of Pneumococcus in Children in England up to 10 Years After 13-Valent Pneumococcal Conjugate Vaccine Introduction: Persistence of Serotypes 3 and 19A and Emergence of 7C

Author

Karen S Tiley, Helen Ratcliffe, Merryn Voysey, Kimberley Jefferies, Gemma Sinclair, Melanie Carr, Rachel Colin-Jones, David Smith, Jaclyn Bowman, Thomas Hart, Rama Kandasamy, Jason Hinds, Katherine Gould, Guy Berbers, Irina Tcherniaeva, Hannah Robinson, Emma Plested, Parvinder Aley, and Matthew D Snape

Subjects
Infectious Diseases, Immunology and Allergy
Abstract

Background Monitoring changes in pharyngeal carriage of pneumococcus in children following 13-valent pneumococcal conjugate vaccine (PCV13) introduction in the United Kingdom in 2010 informs understanding of patterns of invasive pneumococcal disease (IPD) incidence. Methods Nasopharyngeal swabs from healthy children vaccinated with PCV13 according to schedule (2, 4, and 12 months) were cultured and serotyped. Results for children aged 13–48 months were compared between 2014–2015 and 2017–2019 and with children aged 6–12 months (2017–2020). Blood was obtained from a subset of children for pneumococcal serotype-specific immunoglobulin G (IgG). Results Total pneumococcal carriage at 13–48 months was 47.9% (473/988) in 2014–2015 and 51.8% (412/795) in 2017–2019 (P = .10); at age 6–12 months this value was 44.6% (274/615). In 2017–2019, 2.9% (95% confidence interval, 1.8%–4.3%) of children aged 13–48 months carried PCV13 serotypes (mainly 3 [1.5%] and 19A [0.8%]) and >20% carried the additional 20-valent PCV (PCV20) serotypes. Similar proportions of children had IgG ≥0.35 IU/mL for each serotype in 2014–2015 and 2017–2019. Serotype 7C carriage increased significantly (P < .01) between 2014–2015 and 2017–2019. Carriage of PCV20 serotypes 8 and 12F, both major causes of IPD, was rare. Conclusions Introduction of PCV20, if licensed for children, could significantly change the composition of pneumococcal serotypes carried in the pharynx of UK children. Clinical Trials Registration NCT03102840.

Published
2022
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4. Nasopharyngeal carriage of pneumococcus in children in England up to ten years after PCV13 introduction: persistence of serotypes 3 and 19A and emergence of 7C

Author

Karen S, Tiley, Helen, Ratcliffe, Merryn, Voysey, Kimberley, Jefferies, Gemma, Sinclair, Melanie, Carr, Rachel, Colin-Jones, David, Smith, Jaclyn, Bowman, Thomas, Hart, Rama, Kandasamy, Jason, Hinds, Katherine, Gould, Guy, Berbers, Irina, Tcherniaeva, Hannah, Robinson, Emma, Plested, Parvinder, Aley, and Matthew D, Snape

Abstract

Monitoring changes in pharyngeal carriage of pneumococcus in children following 13-valent pneumococcal conjugate vaccine (PCV13) introduction in the UK in 2010 informs understanding of patterns of invasive pneumococcal disease (IPD) incidence.Nasopharyngeal swabs from healthy children vaccinated with PCV13 according to schedule (2, 4, 12 months) were cultured and serotyped. Results for children aged 13-48 months were compared between 2014/15 and 2017/19, and with children aged 6-12 months (2017/20). Blood was obtained from a subset of children for pneumococcal serotype-specific IgG.Total pneumococcal carriage at 13-48 months was 47.9% (473/988) in 2014/15 and 51.8% (412/795) in 2017/19 (p = 0.10); at age 6-12 months this value was 44.6% (274/615). In 2017/19, 2.9% (95% CI 1.8-4.3%) of children aged 13-48 months carried PCV13 serotypes (mainly 3 (1.5%) and 19A (0.8%)) and over 20% carried the additional PCV20 serotypes. Similar proportions of children had IgG ≥0.35 IU/mL for each serotype in 2014/15 and 2017/19.Serotype 7C carriage increased significantly (p 0.01) between 2014/15 and 2017/19. Carriage of PCV20 serotypes 8 and 12F, both major causes of IPD, was rare.Introduction of PCV20, if licensed for children, could significantly change the composition of pneumococcal serotypes carried in the pharynx of UK children.

Published
2022

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

Author

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

Subjects
Pediatrics, Perinatology and Child Health
Abstract

ObjectiveTo understand community seroprevalence of SARS-CoV-2 in children and adolescents. This is vital to understanding the susceptibility of this cohort to COVID-19 and to inform public health policy for disease control such as immunisation.DesignWe conducted a community-based cross-sectional seroprevalence study in participants aged 0–18 years old recruiting from seven regions in England between October 2019 and June 2021 and collecting extensive demographic and symptom data. Serum samples were tested for antibodies against SARS-CoV-2 spike and nucleocapsid proteins using Roche assays processed at UK Health Security Agency laboratories. Prevalence estimates were calculated for six time periods and were standardised by age group, ethnicity and National Health Service region.ResultsPost-first wave (June–August 2020), the (anti-spike IgG) adjusted seroprevalence was 5.2%, varying from 0.9% (participants 10–14 years old) to 9.5% (participants 5–9 years old). By April–June 2021, this had increased to 19.9%, varying from 13.9% (participants 0–4 years old) to 32.7% (participants 15–18 years old). Minority ethnic groups had higher risk of SARS-CoV-2 seropositivity than white participants (OR 1.4, 95% CI 1.0 to 2.0), after adjusting for sex, age, region, time period, deprivation and urban/rural geography. In children ConclusionsApproximately one-third of participants aged 15–18 years old had evidence of antibodies against SARS-CoV-2 prior to the introduction of widespread vaccination. These data demonstrate that ethnic background is independently associated with risk of SARS-CoV-2 infection in children.Trial registration numberNCT04061382.

Published
2022

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

Author

Merryn Voysey, Sue Ann Costa Clemens, Shabir A Madhi, Lily Y Weckx, Pedro M Folegatti, Parvinder K Aley, Brian Angus, Vicky L Baillie, Shaun L Barnabas, Qasim E Bhorat, Sagida Bibi, Carmen Briner, Paola Cicconi, Andrea M Collins, Rachel Colin-Jones, Clare L Cutland, Thomas C Darton, Keertan Dheda, Christopher J A Duncan, Katherine R W Emary, Katie J Ewer, Lee Fairlie, Saul N Faust, Shuo Feng, Daniela M Ferreira, Adam Finn, Anna L Goodman, Catherine M Green, Christopher A Green, Paul T Heath, Catherine Hill, Helen Hill, Ian Hirsch, Susanne H C Hodgson, Alane Izu, Susan Jackson, Daniel Jenkin, Carina C D Joe, Simon Kerridge, Anthonet Koen, Gaurav Kwatra, Rajeka Lazarus, Alison M Lawrie, Alice Lelliott, Vincenzo Libri, Patrick J Lillie, Raburn Mallory, Ana V A Mendes, Eveline P Milan, Angela M Minassian, Alastair McGregor, Hazel Morrison, Yama F Mujadidi, Anusha Nana, Peter J O’Reilly, Sherman D Padayachee, Ana Pittella, Emma Plested, Katrina M Pollock, Maheshi N Ramasamy, Sarah Rhead, Alexandre V Schwarzbold, Nisha Singh, Andrew Smith, Rinn Song, Matthew D Snape, Eduardo Sprinz, Rebecca K Sutherland, Richard Tarrant, Emma C Thomson, M Estée Török, Mark Toshner, David P J Turner, Johan Vekemans, Tonya L Villafana, Marion E E Watson, Christopher J Williams, Alexander D Douglas, Adrian V S Hill, Teresa Lambe, Sarah C Gilbert, Andrew J Pollard, Marites Aban, Fatola Abayomi, Kushala Abeyskera, Jeremy Aboagye, Matthew Adam, Kirsty Adams, James Adamson, Yemi A. Adelaja, Gbadebo Adewetan, Syed Adlou, Khatija Ahmed, Yasmeen Akhalwaya, Saajida Akhalwaya, Andrew Alcock, Aabidah Ali, Elizabeth R. Allen, Lauren Allen, Thamires C. D. S. C Almeida, Mariana P.S. Alves, Fabio Amorim, Foteini Andritsou, Rachel Anslow, Matthew Appleby, Edward H. Arbe-Barnes, Mark P. Ariaans, Beatriz Arns, Laiana Arruda, Paula Azi, Lorena Azi, Gavin Babbage, Catherine Bailey, Kenneth F. Baker, Megan Baker, Natalie Baker, Philip Baker, Lisa Baldwin, Ioana Baleanu, Danieli Bandeira, Anna Bara, Marcella A.S. Barbosa, Debbie Barker, Gavin D. Barlow, Eleanor Barnes, Andrew S. Barr, Jordan R. Barrett, Jessica Barrett, Louise Bates, Alexander Batten, Kirsten Beadon, Emily Beales, Rebecca Beckley, Sandra Belij-Rammerstorfer, Jonathan Bell, Duncan Bellamy, Nancy Bellei, Sue Belton, Adam Berg, Laura Bermejo, Eleanor Berrie, Lisa Berry, Daniella Berzenyi, Amy Beveridge, Kevin R. Bewley, Helen Bexhell, Sutika Bhikha, Asad E. Bhorat, Zaheda E. Bhorat, Else Bijker, Geeta Birch, Sarah Birch, Adam Bird, Olivia Bird, Karen Bisnauthsing, Mustapha Bittaye, Katherine Blackstone, Luke Blackwell, Heather Bletchly, Caitlin L. Blundell, Susannah R. Blundell, Pritesh Bodalia, Bruno C. Boettger, Emma Bolam, Elena Boland, Daan Bormans, Nicola Borthwick, Francesca Bowring, Amy Boyd, Penny Bradley, Tanja Brenner, Phillip Brown, Claire Brown, Charlie Brown-O'Sullivan, Scott Bruce, Emily Brunt, Ruaridh Buchan, William Budd, Yusuf A. Bulbulia, Melanie Bull, Jamie Burbage, Hassan Burhan, Aileen Burn, Karen R. Buttigieg, Nicholas Byard, Ingrid Cabera Puig, Gloria Calderon, Anna Calvert, Susana Camara, Michelangelo Cao, Federica Cappuccini, João R. Cardoso, Melanie Carr, Miles W. Carroll, Andrew Carson-Stevens, Yasmin de M. Carvalho, José A.M. Carvalho, Helen R. Casey, Paul Cashen, Thais Castro, Lucia Carratala Castro, Katrina Cathie, Ana Cavey, José Cerbino-Neto, Jim Chadwick, David Chapman, Sue Charlton, Irina Chelysheva, Oliver Chester, Sunder Chita, Jee-Sun Cho, Liliana Cifuentes, Elizabeth Clark, Matthew Clark, Andrea Clarke, Elizabeth A. Clutterbuck, Sarah L.K. Collins, Christopher P. Conlon, Sean Connarty, Naomi Coombes, Cushla Cooper, Rachel Cooper, Lynne Cornelissen, Tumena Corrah, Catherine Cosgrove, Tony Cox, Wendy E.M. Crocker, Sarah Crosbie, Lorraine Cullen, Dan Cullen, Debora R.M.F. Cunha, Christina Cunningham, Fiona C. Cuthbertson, Suzete N. Farias Da Guarda, Larissa P. da Silva, Brad E. Damratoski, Zsofia Danos, Maria T.D.C. Dantas, Paula Darroch, Mehreen S. Datoo, Chandrabali Datta, Malika Davids, Sarah L. Davies, Hannah Davies, Elizabeth Davis, Judith Davis, John Davis, Maristela M.D. De Nobrega, Lis Moreno De Oliveira Kalid, David Dearlove, Tesfaye Demissie, Amisha Desai, Stefania Di Marco, Claudio Di Maso, Maria I.S. Dinelli, Tanya Dinesh, Claire Docksey, Christina Dold, Tao Dong, Francesca R. Donnellan, Tannyth Dos Santos, Thainá G. dos Santos, Erika Pachecho Dos Santos, Naomi Douglas, Charlotte Downing, Jonathan Drake, Rachael Drake-Brockman, Kimberley Driver, Ruth Drury, Susanna J. Dunachie, Benjamin S. Durham, Lidiana Dutra, Nicholas J.W. Easom, Samual van Eck, Mandy Edwards, Nick J. Edwards, Omar M. El Muhanna, Sean C. Elias, Mike Elmore, Marcus English, Alisgair Esmail, Yakub Moosa Essack, Eoghan Farmer, Mutjaba Farooq, Madi Farrar, Leonard Farrugia, Beverley Faulkner, Sofiya Fedosyuk, Sally Felle, Carla Ferreira Da Silva, Samantha Field, Richard Fisher, Amy Flaxman, James Fletcher, Hazel Fofie, Henry Fok, Karen J. Ford, Jamie Fowler, Pedro H.A. Fraiman, Emma Francis, Marilia M. Franco, John Frater, Marilúcia S.M. Freire, Samantha H. Fry, Sabrina Fudge, Julie Furze, Michelle Fuskova, Pablo Galian-Rubio, Eva Galiza, Harriet Garlant, Madita Gavrila, Ailsa Geddes, Karyna A. Gibbons, Ciaran Gilbride, Hardeep Gill, Sharon Glynn, Kerry Godwin, Karishma Gokani, Ursula Carvalho Goldoni, Maria Goncalves, Isabela G.S. Gonzalez, Jayne Goodwin, Amina Goondiwala, Katherine Gordon-Quayle, Giacomo Gorini, Janet Grab, Lara Gracie, Melanie Greenland, Nicola Greenwood, Johann Greffrath, Marisa M. Groenewald, Leonardo Grossi, Gaurav Gupta, Mark Hackett, Bassam Hallis, Mainga Hamaluba, Elizabeth Hamilton, Joseph Hamlyn, Daniel Hammersley, Aidan T. Hanrath, Brama Hanumunthadu, Stephanie A. Harris, Clair Harris, Tara Harris, Thomas D. Harrison, Daisy Harrison, Thomas C. Hart, Birgit Hartnell, Shadin Hassan, John Haughney, Sophia Hawkins, Jodie Hay, Ian Head, John Henry, Macarena Hermosin Herrera, David B. Hettle, Jennifer Hill, Gina Hodges, Elizea Horne, Mimi M. Hou, Catherine Houlihan, Elizabeth Howe, Nicola Howell, Jonathan Humphreys, Holly E. Humphries, Katrina Hurley, Claire Huson, Angela Hyder-Wright, Catherine Hyams, Sabina Ikram, Alka Ishwarbhai, Monica Ivan, Poppy Iveson, Vidyashankara Iyer, Frederic Jackson, Jeanne De Jager, Shameem Jaumdally, Helen Jeffers, Natasha Jesudason, Bryony Jones, Kathryn Jones, Elizabeth Jones, Christopher Jones, Marianna Rocha Jorge, Aylin Jose, Amar Joshi, Eduardo A.M.S. Júnior, Joanne Kadziola, Reshma Kailath, Faeeza Kana, Konstantinos Karampatsas, Mwila Kasanyinga, Jade Keen, Elizabeth J. Kelly, Dearbhla M. Kelly, Debbie Kelly, Sarah Kelly, David Kerr, Renato de Ávila Kfouri, Liaquat Khan, Baktash Khozoee, Sarah Kidd, Annabel Killen, Jasmin Kinch, Patrick Kinch, Lloyd D.W. King, Thomas B. King, Lucy Kingham, Paul Klenerman, Francesca Knapper, Julian C. Knight, Daniel Knott, Stanislava Koleva, Matilda Lang, Gail Lang, Colin W. Larkworthy, Jessica P.J. Larwood, Rebecca Law, Erica M. Lazarus, Amanda Leach, Emily A. Lees, Nana-Marie Lemm, Alvaro Lessa, Stephanie Leung, Yuanyuan Li, Amelia M. Lias, Kostas Liatsikos, Aline Linder, Samuel Lipworth, Shuchang Liu, Xinxue Liu, Adam Lloyd, Stephanie Lloyd, Lisa Loew, Raquel Lopez Ramon, Leandro Lora, Vicki Lowthorpe, Kleber Luz, Jonathan C. MacDonald, Gordon MacGregor, Meera Madhavan, David O. Mainwaring, Edson Makambwa, Rebecca Makinson, Mookho Malahleha, Ross Malamatsho, Garry Mallett, Kushal Mansatta, Takalani Maoko, Katlego Mapetla, Natalie G. Marchevsky, Spyridoula Marinou, Emma Marlow, Gabriela N. Marques, Paula Marriott, Richard P. Marshall, Julia L. Marshall, Flávia J. Martins, Masebole Masenya, Mduduzi Masilela, Shauna K. Masters, Moncy Mathew, Hosea Matlebjane, Kedidimetse Matshidiso, Olga Mazur, Andrea Mazzella, Hugh McCaughan, Joanne McEwan, Joanna McGlashan, Lorna McInroy, Zoe McIntyre, Daniela McLenaghan, Nicky McRobert, Steve McSwiggan, Clare Megson, Savviz Mehdipour, Wilma Meijs, Renata N.Á. Mendonça, Alexander J. Mentzer, Neginsadat Mirtorabi, Celia Mitton, Sibusiso Mnyakeni, Fiona Moghaddas, Kgaogelo Molapo, Mapule Moloi, Maria Moore, M. Isabel Moraes-Pinto, Marni Moran, Ella Morey, Róisín Morgans, Susan Morris, Sheila Morris, Helen C. Morris, Franca Morselli, Gertraud Morshead, Richard Morter, Lynelle Mottal, Andrew Moultrie, Nathifa Moya, Mushiya Mpelembue, Sibekezelo Msomi, Yvonne Mugodi, Ekta Mukhopadhyay, Jilly Muller, Alasdair Munro, Claire Munro, Sarah Murphy, Philomena Mweu, Celia Hatsuko Myasaki, Gurudutt Naik, Kush Naker, Eleni Nastouli, Abida Nazir, Bongani Ndlovu, Fabio Neffa, Cecilia Njenga, Helena Noal, Andrés Noé, Gabrielle Novaes, Fay L. Nugent, Géssika Nunes, Katie O'Brien, Daniel O'Connor, Miranda Odam, Suzette Oelofse, Blanche Oguti, Victoria Olchawski, Neil J. Oldfield, Marianne G. Oliveira, Catarina Oliveira, Angela Oosthuizen, Paula O'Reilly, Piper Osborne, David R.J. Owen, Lydia Owen, Daniel Owens, Nelly Owino, Mihaela Pacurar, Brenda V.B. Paiva, Edna M.F. Palhares, Susan Palmer, Sivapriyai Parkinson, Helena M.R.T. Parracho, Karen Parsons, Dipak Patel, Bhumika Patel, Faeezah Patel, Kelly Patel, Maia Patrick-Smith, Ruth O. Payne, Yanchun Peng, Elizabeth J. Penn, Anna Pennington, Marco Polo Peralta Alvarez, James Perring, Nicola Perry, Rubeshan Perumal, Sahir Petkar, Tricia Philip, Daniel J. Phillips, Jennifer Phillips, Mary Kgomotso Phohu, Lorinda Pickup, Sonja Pieterse, Jo Piper, Dimitra Pipini, Mary Plank, Joan Du Plessis, Samuel Pollard, Jennifer Pooley, Anil Pooran, Ian Poulton, Claire Powers, Fernando B. Presa, David A. Price, Vivien Price, Marcelo Primeira, Pamela C. Proud, Samuel Provstgaard-Morys, Sophie Pueschel, David Pulido, Sheena Quaid, Ria Rabara, Alexandra Radford, Kajal Radia, Durga Rajapaska, Thurkka Rajeswaran, Alberto San Francisco Ramos, Fernando Ramos Lopez, Tommy Rampling, Jade Rand, Helen Ratcliffe, Tom Rawlinson, David Rea, Byron Rees, Jesús Reiné, Mila Resuello-Dauti, Emilia Reyes Pabon, Carla M. Ribiero, Marivic Ricamara, Alex Richter, Neil Ritchie, Adam J. Ritchie, Alexander J. Robbins, Hannah Roberts, Ryan E. Robinson, Hannah Robinson, Talita T. Rocchetti, Beatriz Pinho Rocha, Sophie Roche, Christine Rollier, Louisa Rose, Amy L. Ross Russell, Lindie Rossouw, Simon Royal, Indra Rudiansyah, Sarah Ruiz, Stephen Saich, Claudia Sala, Jessica Sale, Ahmed M. Salman, Natalia Salvador, Stephannie Salvador, Milla Sampaio, Annette D. Samson, Amada Sanchez-Gonzalez, Helen Sanders, Katherine Sanders, Erika Santos, Mayara F.S. Santos Guerra, Iman Satti, Jack E. Saunders, Caroline Saunders, Aakifah Sayed, Ina Schim van der Loeff, Annina B. Schmid, Ella Schofield, Gavin Screaton, Samiullah Seddiqi, Rameswara R. Segireddy, Roberta Senger, Sonia Serrano, Rajiv Shah, Imam Shaik, Hannah E. Sharpe, Katherine Sharrocks, Robert Shaw, Adam Shea, Amy Shepherd, James G. Shepherd, Farah Shiham, Emad Sidhom, Sarah E. Silk, Antonio Carlos da Silva Moraes, Gilberto Silva-Junior, Laura Silva-Reyes, Anderson D. Silveira, Mariana B.V. Silveira, Jaisi Sinha, Donal T. Skelly, Daniel C. Smith, Nick Smith, Holly E. Smith, David J. Smith, Catherine C. Smith, Airanuédida Soares, Tiago Soares, Carla Solórzano, Guilherme L. Sorio, Kim Sorley, Tiffany Sosa-Rodriguez, Cinthia M.C.D.L. Souza, Bruno S.D.F. Souza, Alessandra R. Souza, Alexandra J. Spencer, Fernanda Spina, Louise Spoors, Lizzie Stafford, Imogen Stamford, Igor Starinskij, Ricardo Stein, Jill Steven, Lisa Stockdale, Lisa V. Stockwell, Louise H. Strickland, Arabella C. Stuart, Ann Sturdy, Natalina Sutton, Anna Szigeti, Abdessamad Tahiri-Alaoui, Rachel Tanner, Carol Taoushanis, Alexander W. Tarr, Keja Taylor, Ursula Taylor, Iona Jennifer Taylor, Justin Taylor, Rebecca te Water Naude, Yrene Themistocleous, Andreas Themistocleous, Merin Thomas, Kelly Thomas, Tonia M. Thomas, Asha Thombrayil, Fawziyah Thompson, Amber Thompson, Kevin Thompson, Ameeka Thompson, Julia Thomson, Viv Thornton-Jones, Patrick J. Tighe, Lygia Accioly Tinoco, Gerlynn Tiongson, Bonolo Tladinyane, Michele Tomasicchio, Adriana Tomic, Susan Tonks, James Towner, Nguyen Tran, Julia Tree, Gerry Trillana, Charlotte Trinham, Rose Trivett, Adam Truby, Betty Lebogang Tsheko, Aadil Turabi, Richard Turner, Cheryl Turner, Marta Ulaszewska, Benjamin R. Underwood, Rachel Varughese, Dennis Verbart, Marije Verheul, Iason Vichos, Taiane Vieira, Claire S. Waddington, Laura Walker, Erica Wallis, Matthew Wand, Deborah Warbick, Theresa Wardell, George Warimwe, Sarah C. Warren, Bridget Watkins, Ekaterina Watson, Stewart Webb, Alice Webb-Bridges, Angela Webster, Jessica Welch, Jeanette Wells, Alison West, Caroline White, Rachel White, Paul Williams, Rachel L. Williams, Rebecca Winslow, Mark Woodyer, Andrew T. Worth, Danny Wright, Marzena Wroblewska, Andy Yao, Rafael Zimmer, Dalila Zizi, Peter Zuidewind, Group, Oxford COVID Vaccine Trial, Toshner, Mark [0000-0002-3969-6143], and Apollo - University of Cambridge Repository

Subjects
Male, COVID-19/prevention & control, 030204 cardiovascular system & hematology, law.invention, South Africa, 0302 clinical medicine, Randomized controlled trial, law, Oxford COVID Vaccine Trial Group, wc_505, Single-Blind Method, 030212 general & internal medicine, Young adult, 11 Medical and Health Sciences, wa_105, Covid19, General Medicine, Articles, Middle Aged, Treatment Outcome, Cohort, Perspective, Female, Brazil, Adult, medicine.medical_specialty, COVID-19 Vaccines, Adolescent, qw_806, qw_805, 03 medical and health sciences, Young Adult, Double-Blind Method, Conjugate vaccine, Internal medicine, General & Internal Medicine, ChAdOx1 nCoV-19, medicine, Humans, Adverse effect, Aged, business.industry, SARS-CoV-2, COVID-19, Viral Vaccines, Vaccine efficacy, Interim analysis, United Kingdom, Clinical trial, bf023de6, business, COVID-19 Vaccines/adverse effects
Abstract

BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. \ud \ud \ud METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. \ud \ud \ud FINDINGS: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. \ud \ud \ud INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. \ud \ud \ud FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca.

Published
2020
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7. Safety and immunogenicity of ChAdOx1 nCoV-19 vaccine administered in a prime-boost regimen in young and old adults (COV002): a single-blind, randomised, controlled, phase 2/3 trial

Author

Maheshi N Ramasamy, Angela M Minassian, Katie J Ewer, Amy L Flaxman, Pedro M Folegatti, Daniel R Owens, Merryn Voysey, Parvinder K Aley, Brian Angus, Gavin Babbage, Sandra Belij-Rammerstorfer, Lisa Berry, Sagida Bibi, Mustapha Bittaye, Katrina Cathie, Harry Chappell, Sue Charlton, Paola Cicconi, Elizabeth A Clutterbuck, Rachel Colin-Jones, Christina Dold, Katherine R W Emary, Sofiya Fedosyuk, Michelle Fuskova, Diane Gbesemete, Catherine Green, Bassam Hallis, Mimi M Hou, Daniel Jenkin, Carina C D Joe, Elizabeth J Kelly, Simon Kerridge, Alison M Lawrie, Alice Lelliott, May N Lwin, Rebecca Makinson, Natalie G Marchevsky, Yama Mujadidi, Alasdair P S Munro, Mihaela Pacurar, Emma Plested, Jade Rand, Thomas Rawlinson, Sarah Rhead, Hannah Robinson, Adam J Ritchie, Amy L Ross-Russell, Stephen Saich, Nisha Singh, Catherine C Smith, Matthew D Snape, Rinn Song, Richard Tarrant, Yrene Themistocleous, Kelly M Thomas, Tonya L Villafana, Sarah C Warren, Marion E E Watson, Alexander D Douglas, Adrian V S Hill, Teresa Lambe, Sarah C Gilbert, Saul N Faust, Andrew J Pollard, Jeremy Aboagye, Kelly Adams, Aabidah Ali, Elizabeth R. Allen, Lauren Allen, Jennifer L. Allison, Foteini Andritsou, Rachel Anslow, Edward H. Arbe-Barnes, Megan Baker, Natalie Baker, Philip Baker, Ioana Baleanu, Debbie Barker, Eleanor Barnes, Jordan R. Barrett, Kelly Barrett, Louise Bates, Alexander Batten, Kirsten Beadon, Rebecca Beckley, Duncan Bellamy, Adam Berg, Laura Bermejo, Eleanor Berrie, Amy Beveridge, Kevin Bewley, Else M. Bijker, Geeta Birch, Luke Blackwell, Heather Bletchly, Caitlin L. Blundell, Susannah R. Blundell, Emma Bolam, Elena Boland, Daan Bormans, Nicola Borthwick, Konstantinos Boukas, Thomas Bower, Francesca Bowring, Amy Boyd, Tanja Brenner, Phillip Brown, Charlie Brown-O'Sullivan, Scott Bruce, Emily Brunt, Jamie Burbage, Joshua Burgoyne, Karen R. Buttigieg, Nicholas Byard, Ingrid Cabera Puig, Susana Camara, Michelangelo Cao, Federica Cappuccini, Melanie Carr, Miles W. Carroll, Paul Cashen, Ana Cavey, Jim Chadwick, Ruth Challis, David Chapman, David Charles, Irina Chelysheva, Jee-Sun Cho, Liliana Cifuentes, Elizabeth Clark, Sarah Collins, Christopher P. Conlon, Naomi S. Coombes, Rachel Cooper, Cushla Cooper, Wendy E.M. Crocker, Sarah Crosbie, Dan Cullen, Christina Cunningham, Fiona Cuthbertson, Brad E. Datoo, Lynne Dando, Mehreen S. Datoo, Chandrabali Datta, Hannah Davies, Sarah Davies, Elizabeth J. Davis, Judith Davis, David Dearlove, Tesfaye Demissie, Stefania Di Marco, Claudio Di Maso, Danielle DiTirro, Claire Docksey, Tao Dong, Francesca R. Donnellan, Naomi Douglas, Charlotte Downing, Jonathan Drake, Rachael Drake-Brockman, Ruth E. Drury, Susanna J. Dunachie, Christopher J. Edwards, Nick J. Edwards, Omar El Muhanna, Sean C. Elias, Ryan S. Elliott, Michael J. Elmore, Marcus Rex English, Sally Felle, Shuo Feng, Carla Ferreira Da Silva, Samantha Field, Richard Fisher, Carine Fixmer, Karen J. Ford, Jamie Fowler, Emma Francis, John Frater, Julie Furze, Pablo Galian-Rubio, Celine Galloway, Harriet Garlant, Madita Gavrila, Felicity Gibbons, Karyna Gibbons, Ciaran Gilbride, Hardeep Gill, Kerry Godwin, Katherine Gordon-Quayle, Giacomo Gorini, Lyndsey Goulston, Caroline Grabau, Lara Gracie, Nichola Graham, Nicola Greenwood, Oliver Griffiths, Gaurav Gupta, Elizabeth Hamilton, Brama Hanumunthadu, Stephanie A. Harris, Tara Harris, Daisy Harrison, Thomas C. Hart, Birgit Hartnell, Louise Haskell, Sophia Hawkins, John Aaron Henry, Macarena Hermosin Herrera, David Hill, Jennifer Hill, Gina Hodges, Susanne H.C. Hodgson, Katie L. Horton, Elizabeth Howe, Nicola Howell, Jessica Howes, Ben Huang, Jonathan Humphreys, Holly E. Humphries, Poppy Iveson, Frederic Jackson, Susan Jackson, Sam Jauregui, Helen Jeffers, Bryony Jones, Christine E. Jones, Elizabeth Jones, Kathryn Jones, Amar Joshi, Reshma Kailath, Jade Keen, Dearbhla M. Kelly, Sarah Kelly, Debbie Kelly, David Kerr, Liaquat Khan, Baktash Khozoee, Annabel Killen, Jasmin Kinch, Lloyd D.W. King, Thomas B. King, Lucy Kingham, Paul Klenerman, Julian C. Knight, Daniel Knott, Stanislava Koleva, Gail Lang, Colin W. Larkworthy, Jessica P.J. Larwood, Rebecca Law, Arlene Lee, Kim Y.N. Lee, Emily A. Lees, Stephanie Leung, Yuanyuan Li, Amelia M. Lias, Aline Linder, Samuel Lipworth, Shuchang Liu, Xinxue Liu, Stephanie Lloyd, Lisa Loew, Raquel Lopez Ramon, Meera Madhavan, David O. Mainwaring, Garry Mallett, Kushal Mansatta, Spyridoula Marinou, Phedra Marius, Emma Marlow, Paula Marriott, Julia L. Marshall, Jane Martin, Shauna Masters, Joanne McEwan, Joanna L. McGlashan, Lorna McInroy, Nicky McRobert, Clare Megson, Alexander J. Mentzer, Neginsadat Mirtorabi, Celia Mitton, Maria Moore, Marni Moran, Ella Morey, Róisín Morgans, Susan J. Morris, Hazel Morrison Morrison, Gertraud Morshead, Richard Morter, Nathifa A. Moya, Ekta Mukhopadhyay, Jilly Muller, Claire Munro, Sarah Murphy, Philomena Mweu, Andrés Noé, Fay L. Nugent, Katie O'Brien, Daniel O'Connor, Blanché Oguti, Victoria Olchawski, Catarina Oliveira, Peter John O'Reilly, Piper Osborne, Lydia Owen, Nelly Owino, Panagiotis Papageorgiou, Helena Parracho, Karen Parsons, Bhumika Patel, Maia Patrick-Smith, Yanchun Peng, Elizabeth J. Penn, Marco Polo Peralta-Alvarez, James Perring, Christos Petropoulos, Daniel J. Phillips, Dimitra Pipini, Samuel Pollard, Ian Poulton, Danny Pratt, Laura Presland, Pamela C. Proud, Samuel Provstgaard-Morys, Sophie Pueschel, David Pulido, Ria Rabara, Kajal Radia, Durga Rajapaska, Fernando Ramos Lopez, Helen Ratcliffe, Sara Rayhan, Byron Rees, Emilia Reyes Pabon, Hannah Roberts, Isla Robertson, Sophie Roche, Christine S. Rollier, Rossana Romani, Zoe Rose, Indra Rudiansyah, Sabeha Sabheha, Stephannie Salvador, Helen Sanders, Katherine Sanders, Iman Satti, Chloe Sayce, Annina B. Schmid, Ella Schofield, Gavin Screaton, Cynthia Sedik, Samiullah Seddiqi, Rameswara R. Segireddy, Beatrice Selby, Imam Shaik, Hannah R. Sharpe, Robert Shaw, Adam Shea, Sarah Silk, Laura Silva-Reyes, Donal T. Skelly, David J. Smith, Daniel C. Smith, Nicholas Smith, Alexandra J. Spencer, Louise Spoors, Elizabeth Stafford, Imogen Stamford, Lisa Stockdale, David Stockley, Lisa V. Stockwell, Matthew Stokes, Louise H. Strickland, Arabella Stuart, Sulaiman Sulaiman, Eloise Summerton, Zoe Swash, Anna Szigeti, Abdessamad Tahiri-Alaoui, Rachel Tanner, Iona Taylor, Keja Taylor, Ursula Taylor, Rebecca te Water Naude, Andreas Themistocleous, Merin Thomas, Tonia M. Thomas, Amber Thompson, Kevin Thompson, Viv Thornton-Jones, Lan Tinh, Adriana Tomic, Susan Tonks, James Towner, Nguyen Tran, Julian A. Tree, Adam Truby, Cheryl Turner, Richard Turner, Marta Ulaszewska, Rachel Varughese, Dennis Verbart, Marije K. Verheul, Iason Vichos, Laura Walker, Matthew E. Wand, Bridget Watkins, Jessica Welch, Alison J. West, Caroline White, Rachel White, Paul Williams, Mark Woodyer, Andrew T. Worth, Daniel Wright, Terri Wrin, Xin Li Yao, Diana-Andreea Zbarcea, and Dalila Zizi

Subjects
Adult, Male, Pediatrics, medicine.medical_specialty, COVID-19 Vaccines, Adolescent, Immunization, Secondary, Department of Error, 030204 cardiovascular system & hematology, law.invention, Young Adult, 03 medical and health sciences, Immunogenicity, Vaccine, 0302 clinical medicine, Randomized controlled trial, law, ChAdOx1 nCoV-19, medicine, Humans, Single-Blind Method, 030212 general & internal medicine, Young adult, Adverse effect, Aged, Aged, 80 and over, Reactogenicity, SARS-CoV-2, business.industry, Age Factors, COVID-19, Articles, General Medicine, Middle Aged, Clinical trial, Vaccination, Regimen, Immunoglobulin G, Cohort, Female, business
Abstract

BACKGROUND: Older adults (aged ≥70 years) are at increased risk of severe disease and death if they develop COVID-19 and are therefore a priority for immunisation should an efficacious vaccine be developed. Immunogenicity of vaccines is often worse in older adults as a result of immunosenescence. We have reported the immunogenicity of a novel chimpanzee adenovirus-vectored vaccine, ChAdOx1 nCoV-19, in young adults, and now describe the safety and immunogenicity of this vaccine in a wider range of participants, including adults aged 70 years and older. METHODS: In this report of the phase 2 component of a single-blind, randomised, controlled, phase 2/3 trial (COV002), healthy adults aged 18 years and older were enrolled at two UK clinical research facilities, in an age-escalation manner, into 18-55 years, 56-69 years, and 70 years and older immunogenicity subgroups. Participants were eligible if they did not have severe or uncontrolled medical comorbidities or a high frailty score (if aged ≥65 years). First, participants were recruited to a low-dose cohort, and within each age group, participants were randomly assigned to receive either intramuscular ChAdOx1 nCoV-19 (2·2 × 1010 virus particles) or a control vaccine, MenACWY, using block randomisation and stratified by age and dose group and study site, using the following ratios: in the 18-55 years group, 1:1 to either two doses of ChAdOx1 nCoV-19 or two doses of MenACWY; in the 56-69 years group, 3:1:3:1 to one dose of ChAdOx1 nCoV-19, one dose of MenACWY, two doses of ChAdOx1 nCoV-19, or two doses of MenACWY; and in the 70 years and older, 5:1:5:1 to one dose of ChAdOx1 nCoV-19, one dose of MenACWY, two doses of ChAdOx1 nCoV-19, or two doses of MenACWY. Prime-booster regimens were given 28 days apart. Participants were then recruited to the standard-dose cohort (3·5-6·5 × 1010 virus particles of ChAdOx1 nCoV-19) and the same randomisation procedures were followed, except the 18-55 years group was assigned in a 5:1 ratio to two doses of ChAdOx1 nCoV-19 or two doses of MenACWY. Participants and investigators, but not staff administering the vaccine, were masked to vaccine allocation. The specific objectives of this report were to assess the safety and humoral and cellular immunogenicity of a single-dose and two-dose schedule in adults older than 55 years. Humoral responses at baseline and after each vaccination until 1 year after the booster were assessed using an in-house standardised ELISA, a multiplex immunoassay, and a live severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) microneutralisation assay (MNA80). Cellular responses were assessed using an ex-vivo IFN-γ enzyme-linked immunospot assay. The coprimary outcomes of the trial were efficacy, as measured by the number of cases of symptomatic, virologically confirmed COVID-19, and safety, as measured by the occurrence of serious adverse events. Analyses were by group allocation in participants who received the vaccine. Here, we report the preliminary findings on safety, reactogenicity, and cellular and humoral immune responses. This study is ongoing and is registered with ClinicalTrials.gov, NCT04400838, and ISRCTN, 15281137. FINDINGS: Between May 30 and Aug 8, 2020, 560 participants were enrolled: 160 aged 18-55 years (100 assigned to ChAdOx1 nCoV-19, 60 assigned to MenACWY), 160 aged 56-69 years (120 assigned to ChAdOx1 nCoV-19: 40 assigned to MenACWY), and 240 aged 70 years and older (200 assigned to ChAdOx1 nCoV-19: 40 assigned to MenACWY). Seven participants did not receive the boost dose of their assigned two-dose regimen, one participant received the incorrect vaccine, and three were excluded from immunogenicity analyses due to incorrectly labelled samples. 280 (50%) of 552 analysable participants were female. Local and systemic reactions were more common in participants given ChAdOx1 nCoV-19 than in those given the control vaccine, and similar in nature to those previously reported (injection-site pain, feeling feverish, muscle ache, headache), but were less common in older adults (aged ≥56 years) than younger adults. In those receiving two standard doses of ChAdOx1 nCoV-19, after the prime vaccination local reactions were reported in 43 (88%) of 49 participants in the 18-55 years group, 22 (73%) of 30 in the 56-69 years group, and 30 (61%) of 49 in the 70 years and older group, and systemic reactions in 42 (86%) participants in the 18-55 years group, 23 (77%) in the 56-69 years group, and 32 (65%) in the 70 years and older group. As of Oct 26, 2020, 13 serious adverse events occurred during the study period, none of which were considered to be related to either study vaccine. In participants who received two doses of vaccine, median anti-spike SARS-CoV-2 IgG responses 28 days after the boost dose were similar across the three age cohorts (standard-dose groups: 18-55 years, 20 713 arbitrary units [AU]/mL [IQR 13 898-33 550], n=39; 56-69 years, 16 170 AU/mL [10 233-40 353], n=26; and ≥70 years 17 561 AU/mL [9705-37 796], n=47; p=0·68). Neutralising antibody titres after a boost dose were similar across all age groups (median MNA80 at day 42 in the standard-dose groups: 18-55 years, 193 [IQR 113-238], n=39; 56-69 years, 144 [119-347], n=20; and ≥70 years, 161 [73-323], n=47; p=0·40). By 14 days after the boost dose, 208 (>99%) of 209 boosted participants had neutralising antibody responses. T-cell responses peaked at day 14 after a single standard dose of ChAdOx1 nCoV-19 (18-55 years: median 1187 spot-forming cells [SFCs] per million peripheral blood mononuclear cells [IQR 841-2428], n=24; 56-69 years: 797 SFCs [383-1817], n=29; and ≥70 years: 977 SFCs [458-1914], n=48). INTERPRETATION: ChAdOx1 nCoV-19 appears to be better tolerated in older adults than in younger adults and has similar immunogenicity across all age groups after a boost dose. Further assessment of the efficacy of this vaccine is warranted in all age groups and individuals with comorbidities. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midlands NIHR Clinical Research Network, and AstraZeneca.

Published
2020

8. Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial

Author

Pedro M Folegatti, Katie J Ewer, Parvinder K Aley, Brian Angus, Stephan Becker, Sandra Belij-Rammerstorfer, Duncan Bellamy, Sagida Bibi, Mustapha Bittaye, Elizabeth A Clutterbuck, Christina Dold, Saul N Faust, Adam Finn, Amy L Flaxman, Bassam Hallis, Paul Heath, Daniel Jenkin, Rajeka Lazarus, Rebecca Makinson, Angela M Minassian, Katrina M Pollock, Maheshi Ramasamy, Hannah Robinson, Matthew Snape, Richard Tarrant, Merryn Voysey, Catherine Green, Alexander D Douglas, Adrian V S Hill, Teresa Lambe, Sarah C Gilbert, Andrew J Pollard, Jeremy Aboagye, Kelly Adams, Aabidah Ali, Elizabeth Allen, Jennifer L. Allison, Rachel Anslow, Edward H. Arbe-Barnes, Gavin Babbage, Kenneth Baillie, Megan Baker, Natalie Baker, Philip Baker, Ioana Baleanu, Juliana Ballaminut, Eleanor Barnes, Jordan Barrett, Louise Bates, Alexander Batten, Kirsten Beadon, Rebecca Beckley, Eleanor Berrie, Lisa Berry, Amy Beveridge, Kevin R. Bewley, Else Margreet Bijker, Tracey Bingham, Luke Blackwell, Caitlin L. Blundell, Emma Bolam, Elena Boland, Nicola Borthwick, Thomas Bower, Amy Boyd, Tanja Brenner, Philip D. Bright, Charlie Brown-O'Sullivan, Emily Brunt, Jamie Burbage, Sharon Burge, Karen R. Buttigieg, Nicholas Byard, Ingrid Cabera Puig, Anna Calvert, Susana Camara, Michelangelo Cao, Federica Cappuccini, Melanie Carr, Miles W. Carroll, Victoria Carter, Katrina Cathie, Ruth J. Challis, Sue Charlton, Irina Chelysheva, Jee-Sun Cho, Paola Cicconi, Liliana Cifuentes, Helen Clark, Elizabeth Clark, Tom Cole, Rachel Colin-Jones, Christopher P. Conlon, Aislinn Cook, Naomi S. Coombes, Rachel Cooper, Catherine A. Cosgrove, Karen Coy, Wendy E.M. Crocker, Christina J. Cunningham, Brad E. Damratoski, Lynne Dando, Mehreen S. Datoo, Hannah Davies, Hans De Graaf, Tesfaye Demissie, Claudio Di Maso, Isabelle Dietrich, Tao Dong, Francesca R. Donnellan, Naomi Douglas, Charlotte Downing, Jonathan Drake, Rachael Drake-Brockman, Ruth Elizabeth Drury, Susanna Jane Dunachie, Nick J. Edwards, Frances D.L. Edwards, Chris J. Edwards, Sean C. Elias, Michael J. Elmore, Katherine R.W. Emary, Marcus Rex English, Susanne Fagerbrink, Sally Felle, Shuo Feng, Samantha Field, Carine Fixmer, Clare Fletcher, Karen J. Ford, Jamie Fowler, Polly Fox, Emma Francis, John Frater, Julie Furze, Michelle Fuskova, Eva Galiza, Diane Gbesemete, Ciaran Gilbride, Kerry Godwin, Giacomo Gorini, Lyndsey Goulston, Caroline Grabau, Lara Gracie, Zoe Gray, Lucy Belle Guthrie, Mark Hackett, Sandro Halwe, Elizabeth Hamilton, Joseph Hamlyn, Brama Hanumunthadu, Irasha Harding, Stephanie A. Harris, Andrew Harris, Daisy Harrison, Clare Harrison, Thomas C. Hart, Louise Haskell, Sophia Hawkins, Ian Head, John Aaron Henry, Jennifer Hill, Susanne H.C. Hodgson, Mimi M. Hou, Elizabeth Howe, Nicola Howell, Cecilia Hutlin, Sabina Ikram, Catherine Isitt, Poppy Iveson, Susan Jackson, Frederic Jackson, Sir William James, Megan Jenkins, Elizabeth Jones, Kathryn Jones, Christine E. Jones, Bryony Jones, Reshma Kailath, Konstantinos Karampatsas, Jade Keen, Sarah Kelly, Dearbhla Kelly, David Kerr, Simon Kerridge, Liaquat Khan, Uzma Khan, Annabel Killen, Jasmin Kinch, Thomas B. King, Lloyd King, Jade King, Lucy Kingham-Page, Paul Klenerman, Francesca Knapper, Julian C. Knight, Daniel Knott, Stanislava Koleva, Alexandra Kupke, Colin W. Larkworthy, Jessica P.J. Larwood, Anna Laskey, Alison M. Lawrie, Arlene Lee, Kim Yee Ngan Lee, Emily A Lees, Helen Legge, Alice Lelliott, Nana-Marie Lemm, Amelia M. Lias, Aline Linder, Samuel Lipworth, Xinxue Liu, Shuchang Liu, Raquel Lopez Ramon, May Lwin, Francesca Mabesa, Meera Madhavan, Garry Mallett, Kushal Mansatta, Ines Marcal, Spyridoula Marinou, Emma Marlow, Julia L. Marshall, Jane Martin, Joanne McEwan, Lorna McInroy, Gretchen Meddaugh, Alexander J. Mentzer, Neginsadat Mirtorabi, Maria Moore, Edward Moran, Ella Morey, Victoria Morgan, Susan Jane Morris, Hazel Morrison, Gertraud Morshead, Richard Morter, Yama F. Mujadidi, Jilly Muller, Tatiana Munera-Huertas, Claire Munro, Alasdair Munro, Sarah Murphy, Vincent J. Munster, Philomena Mweu, Andrés Noé, Fay L. Nugent, Elizabeth Nuthall, Katie O'Brien, Daniel O'Connor, Blanché Oguti, Jennifer L. Oliver, Catarina Oliveira, Peter John O'Reilly, Mairead Osborn, Piper Osborne, Cathy Owen, Daniel Owens, Nelly Owino, Mihaela Pacurar, Kaye Parker, Helena Parracho, Maia Patrick-Smith, Victoria Payne, Jennifer Pearce, Yanchun Peng, Marco Polo Peralta Alvarez, James Perring, Katja Pfafferott, Dimitra Pipini, Emma Plested, Helen Pluess-Hall, Katrina Pollock, Ian Poulton, Laura Presland, Samuel Provstgaard-Morys, David Pulido, Kajal Radia, Fernando Ramos Lopez, Jade Rand, Helen Ratcliffe, Thomas Rawlinson, Sarah Rhead, Amy Riddell, Adam John Ritchie, Hannah Roberts, Joanna Robson, Sophie Roche, Cornelius Rohde, Christine S. Rollier, Rossana Romani, Indra Rudiansyah, Stephen Saich, Sara Sajjad, Stephannie Salvador, Lidia Sanchez Riera, Helen Sanders, Katherine Sanders, Shari Sapaun, Chloe Sayce, Ella Schofield, Gavin Screaton, Beatrice Selby, Calum Semple, Hannah R. Sharpe, Imam Shaik, Adam Shea, Holly Shelton, Sarah Silk, Laura Silva-Reyes, Donal T. Skelly, Heather Smee, Catherine C. Smith, David J. Smith, Rinn Song, Alexandra J. Spencer, Elizabeth Stafford, Amy Steele, Elena Stefanova, Lisa Stockdale, Anna Szigeti, Abdessamad Tahiri-Alaoui, Moira Tait, Helen Talbot, Rachel Tanner, Iona Jennifer Taylor, Victoria Taylor, Rebecca Te Water Naude, Nazia Thakur, Yrene Themistocleous, Andreas Themistocleous, Merin Thomas, Tonia M. Thomas, Amber Thompson, Samantha Thomson-Hill, Jennifer Tomlins, Susan Tonks, James Towner, Nguyen Tran, Julia A. Tree, Adam Truby, Kate Turkentine, Cheryl Turner, Nicola Turner, Sally Turner, Toby Tuthill, Marta Ulaszewska, Rachel Varughese, Neeltje Van Doremalen, Kristin Veighey, Marije K. Verheul, Iason Vichos, Elia Vitale, Laura Walker, Marion E.E. Watson, Benjamin Welham, Julie Wheat, Caroline White, Rachel White, Andrew T. Worth, Danny Wright, Suzie Wright, Xin Li Yao, Yasmine Yau, and Hodgson, S

Subjects
Male, T-Lymphocytes, Booster dose, 030204 cardiovascular system & hematology, Antibodies, Viral, law.invention, 0302 clinical medicine, Immunogenicity, Vaccine, Randomized controlled trial, law, Oxford COVID Vaccine Trial Group, Medicine, Single-Blind Method, 030212 general & internal medicine, 11 Medical and Health Sciences, Viral Vaccine, Immunogenicity, Covid19, General Medicine, Analgesics, Non-Narcotic, Vaccination, Spike Glycoprotein, Coronavirus, Female, Coronavirus Infections, Life Sciences & Biomedicine, Adult, medicine.medical_specialty, COVID-19 Vaccines, UNCOVER, Genetic Vectors, Pneumonia, Viral, Immunization, Secondary, Department of Error, Article, 03 medical and health sciences, Betacoronavirus, Medicine, General & Internal, Internal medicine, General & Internal Medicine, Humans, Adverse effect, Pandemics, Acetaminophen, Reactogenicity, Science & Technology, business.industry, SARS-CoV-2, COVID-19, Viral Vaccines, Antibodies, Neutralizing, United Kingdom, Clinical trial, Immunoglobulin G, Adenoviruses, Simian, business, ACUTE RESPIRATORY SYNDROME
Abstract

Background: The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) might be curtailed by vaccination. We assessed the safety, reactogenicity, and immunogenicity of a viral vectored coronavirus vaccine that expresses the spike protein of SARS-CoV-2. Methods: We did a phase 1/2, single-blind, randomised controlled trial in five trial sites in the UK of a chimpanzee adenovirus-vectored vaccine (ChAdOx1 nCoV-19) expressing the SARS-CoV-2 spike protein compared with a meningococcal conjugate vaccine (MenACWY) as control. Healthy adults aged 18–55 years with no history of laboratory confirmed SARS-CoV-2 infection or of COVID-19-like symptoms were randomly assigned (1:1) to receive ChAdOx1 nCoV-19 at a dose of 5 × 10 10 viral particles or MenACWY as a single intramuscular injection. A protocol amendment in two of the five sites allowed prophylactic paracetamol to be administered before vaccination. Ten participants assigned to a non-randomised, unblinded ChAdOx1 nCoV-19 prime-boost group received a two-dose schedule, with the booster vaccine administered 28 days after the first dose. Humoral responses at baseline and following vaccination were assessed using a standardised total IgG ELISA against trimeric SARS-CoV-2 spike protein, a muliplexed immunoassay, three live SARS-CoV-2 neutralisation assays (a 50% plaque reduction neutralisation assay [PRNT 50]; a microneutralisation assay [MNA 50, MNA 80, and MNA 90]; and Marburg VN), and a pseudovirus neutralisation assay. Cellular responses were assessed using an ex-vivo interferon-γ enzyme-linked immunospot assay. The co-primary outcomes are to assess efficacy, as measured by cases of symptomatic virologically confirmed COVID-19, and safety, as measured by the occurrence of serious adverse events. Analyses were done by group allocation in participants who received the vaccine. Safety was assessed over 28 days after vaccination. Here, we report the preliminary findings on safety, reactogenicity, and cellular and humoral immune responses. The study is ongoing, and was registered at ISRCTN, 15281137, and ClinicalTrials.gov, NCT04324606. Findings: Between April 23 and May 21, 2020, 1077 participants were enrolled and assigned to receive either ChAdOx1 nCoV-19 (n=543) or MenACWY (n=534), ten of whom were enrolled in the non-randomised ChAdOx1 nCoV-19 prime-boost group. Local and systemic reactions were more common in the ChAdOx1 nCoV-19 group and many were reduced by use of prophylactic paracetamol, including pain, feeling feverish, chills, muscle ache, headache, and malaise (all p80 and in 35 (100%) participants when measured in PRNT 50. After a booster dose, all participants had neutralising activity (nine of nine in MNA 80 at day 42 and ten of ten in Marburg VN on day 56). Neutralising antibody responses correlated strongly with antibody levels measured by ELISA (R 2=0·67 by Marburg VN; p

Published
2020
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10. Biotech branding: Victoria’s plan to cash in on the ‘Biotechnology Revolution’

Author

Helen Ratcliffe

Subjects
International investment, business.industry, Project commissioning, media_common.quotation_subject, Cornerstone, Plan (drawing), Biotechnology, State (polity), Publishing, Management of Technology and Innovation, Cash, Economics, Marketing, business, media_common, Strategic development
Abstract

Industry policy for the development of knowledge and new-technology based industries increasingly builds on international investment as its cornerstone. This paper examines the Victorian state government's biotechnology strategic development plan, using a state-driven branding exercise, as an example of this policy. Policy suggestions are developed to fill major strategic gaps in the state plan.

Published
2002
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11. Fit For Purpose And Cost Effective Integrated Operations Implementation For Mature Assets In Maersk Oil North Sea UK Limited

Author

Helen Ratcliffe and Claus G. Bjerregaard

Subjects
Operations management, Business, Integrated operations, Manufacturing engineering
Abstract

Integrated Operation (IO) is often perceived as a long term, high cost commitment for an organisation. This perception often makes it difficult to gain the senior sponsorship required to get a programme off the ground for mature assets. This paper outlines how Maersk Oil North Sea UK Limited (Maersk Oil UK) designed and delivered a project, which generated real business value for mature assets within a short timeframe. Key focus in the justification, design and implementation of the project, was the ability to deliver a solution that fitted the business needs and gave immediate value without compromising future opportunities. The project was designed and implemented as the first step towards and proof of the concept for Integration Operations solutions with focus on production optimisation and reservoir management within Maersk Oil UK. The key business process focus was on well test automation, well and reservoir monitoring and production optimisation. All technologies used were readily available and only mature software solutions were used. Part of the required technology was already available in the company however without using the full potential. The paper describes the approach to, and how senior business sponsorship was obtained and retained, how business needs were identified and addressed, how the technology requirements were satisfied and how this influenced the work flow and operation. The paper includes what made the project succeed and why some of the initiatives were less successful. Most importantly, the paper explains how the capabilities developed and delivered in excess of the investment within the projects implementation phase and how Maersk Oil UK continues to gain value of the mature assets. Summary: Full project cycle 1.5 yearsScope includes 3 subsea operated hubs for 8 fields with a total of 45 producers, 13 water injectors and 2 gas injectorsPayback within the project lifecycle.

Published
2011
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12. Change Management Made Easy, A Practical Approach to Change Management for Digital Oil Field Programmes

Author

Gary McMillan and Fiona Helen Ratcliffe

Subjects
Process management, Change management, Business
Abstract

Change management means different things to different people. Essentially change management should be an iterative process that utilises a set of organisation-specific tools and techniques to help an entity and its people transition from a current state to a sustainable desired state. When executed effectively, change management will minimise management risk and maximise return on investment (ROI). Although every change initiative is unique, this paper aims to provide you with an insight into what activities and deliverables could be considered at each phase to maximise the benefits obtained from a clear and practical approach to change management and how the approach can be tailored and or scaled. Our proven approach is practical, heavily integrated with good programme/project management, and focused on the delivery of tangible business benefits. We will exam in greater detail the five "Es" that underpin our methodology: Explore, Expose, Engage, Educate and Embed. Multiple common reasons for failure will be explored and practical steps to mitigate these will be explained. A demonstration of Science Applications International Corporation's (SAIC's) Practical Approach to Change Management is covered as a case study and noted throughout. This is based on a programme we recently worked on with a major North Sea operator. This was a digital oil field programme that has been recognised as the pacesetter within a global network of related initiatives. The intended audience for this paper is people who are planning, designing and carrying out change and communication efforts in support of the digital oil field project, primarily the project team and commissioning manager. However, the principles of this practical approach to change management are applicable to any organisational change activity in any industry. Many myths exist about change management, and we aim to address at least ten of these throughout this paper in an attempt to debunk them for you.

Published
2008
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