1. Reactogenicity and immunogenicity after a late second dose or a third dose of ChAdOx1 nCoV-19 in the UK: a substudy of two randomised controlled trials (COV001 and COV002)
- Author
-
Jordan R. Barrett, Adam Finn, Julie Furze, Rajeka Lazarus, Robert Aley, Emma Plested, Nicholas Byard, Alison M. Lawrie, Jack E. Saunders, Catherine C. Smith, Katie J. Ewer, Hannah Davies, Amber Thompson, Jonathan Kwok, Danielle Woods, Luke Blackwell, M N Ramasamy, Wanwisa Dejnirattisai, Hannah Roberts, Conor Whelan, Elizabeth F Jones, Vincenzo Libri, Mutjaba Ghulam Farooq, D Jenkin, D Bellamy, Mimi M. Hou, Alexander D. Douglas, Sarah Kelly, Adrian V. S. Hill, Sarah C. Gilbert, Christine S. Rollier, Megan Baker, Matthew Rajan, Liaquat Khan, E. Thomson, Amy Boyd, Rebecca Beckley, Phillip Baker, Stanislava Koleva, Louise Bates, Simon Kerridge, David J. Smith, Emma Francis, Christina Dold, Brian Angus, Christopher J A Duncan, Raquel Lopez Ramon, Andrew Smith, Alice Bridges-Webb, Thomas C. Hart, R Song, O Mazur, L Silva-Reyes, Claudio Di Maso, Rabiullah Noristani, Patrick J. Lillie, Marco Polo Peralta Alvarez, Matthew D. Snape, Wendy E.M. Crocker, Patrick Kinch, Charles H. Brown, Jasmin Kinch, Angela M. Minassian, M Bittaye, Jilly Muller, Emma V. Sheehan, J Aboagye, Anna L. Goodman, Iain Turnbull, Julia L. Marshall, Kirsten Beadon, Tanya Dinesh, R Makinson, Hannah Sharpe, Indra Rudiansyah, Jade Keen, Yama F Mujadidi, Laura L. Walker, Marta Ulaszewska, Baktash Khozoee, Jonathan Bell, Cameron Bissett, Robert Shaw, E Howe, Amy Beveridge, Cheryl Turner, Holly Smith, Karly Tang, Federica Cappuccini, Syed Adlou, Juthathip Mongkolsapaya, Estée M. Török, Spyridoula Marinou, Joanne McEwan, Rachel Cooper, David P. J. Turner, Merin Thomas, Tonia M. Thomas, Nicola Greenwood, Gavin R. Screaton, Sally Felle, S Bibi, Carla Ferreira Da Silva, P M Folegatti, Jolynne Mokaya, Sophia Hawkins, Elizabeth A. Clutterbuck, Ian D. Poulton, Andy Yao, Reece Mabbett, Christopher A Green, Emma Marlow, Mark Toshner, Heather Bletchly, Alexandra J. Spencer, Rebecca K. Sutherland, Leila Godfrey, Eva P. Galiza, Sarah Williams, Andrew J. Pollard, Saul N. Faust, Grace Li, Mwila Kasanyinga, Nicola Howell, Aabidah Ali, Daisy Harrison, Thomas C. Darton, Samiullah Seddiqi, David J. Kerr, Gertraud Morshead, Rachael Drake-Brockman, Aline Linder, Jamie Fowler, Sandra Belij-Rammerstorfer, Susana Camara, Colin W. Larkworthy, Sophie Davies, Marion E. Watson, Parvinder K. Aley, Bryn Horsington, Sean C. Elias, Adam J. Ritchie, Nelly Owino, David Pulido-Gomez, Michelle Fuskova, Alastair McGregor, Hannah Robinson, Fei Long, Rachel Anslow, Karen J. Ford, Daniela M. Ferreira, Katherine R. W. Emary, Ella Morey, Amy Flaxman, Paul T. Heath, Katrina M Pollock, Liliana Cifuentes Gutierrez, Samuel Provstgaard-Morys, Arabella Stuart, Helen Sanders, Anna Szigeti, Rachel White, Francesca R. Donnellan, Catherine M. Green, Katherine Sanders, N G Marchevsky, Andrea M. Collins, Merryn Voysey, Kushalinii Hillson, Teresa Lambe, Philomena Mweu, Chris Williams, Iason Vichos, Daniel B. Wright, Carina Citra Dewi Joe, Tesfaye Demissie, Rose Trivett, Richard Morter, Helen Hill, Judith Davies, Emily A. Lees, Nisha Singh, Ana Gibertoni Cruz, P Cicconi, Abigail Platt, Fernando Ramos Lopez, Nguyen Tran, and group, Oxford COVID Vaccine Trial
- Subjects
Adult ,Male ,medicine.medical_specialty ,COVID-19 Vaccines ,Time Factors ,Coronavirus disease 2019 (COVID-19) ,VACCINE ,law.invention ,Medicine, General & Internal ,Immunogenicity, Vaccine ,Randomized controlled trial ,law ,Internal medicine ,ChAdOx1 nCoV-19 ,General & Internal Medicine ,medicine ,Humans ,11 Medical and Health Sciences ,Randomized Controlled Trials as Topic ,Reactogenicity ,Science & Technology ,business.industry ,Immunogenicity ,Comment ,Vaccination ,General Medicine ,Middle Aged ,Engineering and Physical Sciences ,United Kingdom ,Oxford COVID Vaccine Trial group ,Clinical research ,Cohort ,Leukocytes, Mononuclear ,Female ,business ,Life Sciences & Biomedicine - Abstract
Background COVID-19 vaccine supply shortages are causing concerns about compromised immunity in some countries as the interval between the first and second dose becomes longer. Conversely, countries with no supply constraints are considering administering a third dose. We assessed the persistence of immunogenicity after a single dose of ChAdOx1 nCoV-19 (AZD1222), immunity after an extended interval (44–45 weeks) between the first and second dose, and response to a third dose as a booster given 28–38 weeks after the second dose. Methods In this substudy, volunteers aged 18–55 years who were enrolled in the phase 1/2 (COV001) controlled trial in the UK and had received either a single dose or two doses of 5 × 1010 viral particles were invited back for vaccination. Here we report the reactogenicity and immunogenicity of a delayed second dose (44–45 weeks after first dose) or a third dose of the vaccine (28–38 weeks after second dose). Data from volunteers aged 18–55 years who were enrolled in either the phase 1/2 (COV001) or phase 2/3 (COV002), single-blinded, randomised controlled trials of ChAdOx1 nCoV-19 and who had previously received a single dose or two doses of 5 × 1010 viral particles are used for comparison purposes. COV001 is registered with ClinicalTrials.gov, NCT04324606, and ISRCTN, 15281137, and COV002 is registered with ClinicalTrials.gov, NCT04400838, and ISRCTN, 15281137, and both are continuing but not recruiting. Findings Between March 11 and 21, 2021, 90 participants were enrolled in the third-dose boost substudy, of whom 80 (89%) were assessable for reactogenicity, 75 (83%) were assessable for evaluation of antibodies, and 15 (17%) were assessable for T-cells responses. The two-dose cohort comprised 321 participants who had reactogenicity data (with prime-boost interval of 8–12 weeks: 267 [83%] of 321; 15–25 weeks: 24 [7%]; or 44–45 weeks: 30 [9%]) and 261 who had immunogenicity data (interval of 8–12 weeks: 115 [44%] of 261; 15–25 weeks: 116 [44%]; and 44–45 weeks: 30 [11%]). 480 participants from the single-dose cohort were assessable for immunogenicity up to 44–45 weeks after vaccination. Antibody titres after a single dose measured approximately 320 days after vaccination remained higher than the titres measured at baseline (geometric mean titre of 66·00 ELISA units [EUs; 95% CI 47·83–91·08] vs 1·75 EUs [1·60–1·93]). 32 participants received a late second dose of vaccine 44–45 weeks after the first dose, of whom 30 were included in immunogenicity and reactogenicity analyses. Antibody titres were higher 28 days after vaccination in those with a longer interval between first and second dose than for those with a short interval (median total IgG titre: 923 EUs [IQR 525–1764] with an 8–12 week interval; 1860 EUs [917–4934] with a 15–25 week interval; and 3738 EUs [1824–6625] with a 44–45 week interval). Among participants who received a third dose of vaccine, antibody titres (measured in 73 [81%] participants for whom samples were available) were significantly higher 28 days after a third dose (median total IgG titre: 3746 EUs [IQR 2047–6420]) than 28 days after a second dose (median 1792 EUs [IQR 899–4634]; Wilcoxon signed rank test p=0·0043). T-cell responses were also boosted after a third dose (median response increased from 200 spot forming units [SFUs] per million peripheral blood mononuclear cells [PBMCs; IQR 127–389] immediately before the third dose to 399 SFUs per milion PBMCs [314–662] by day 28 after the third dose; Wilcoxon signed rank test p=0·012). Reactogenicity after a late second dose or a third dose was lower than reactogenicity after a first dose. Interpretation An extended interval before the second dose of ChAdOx1 nCoV-19 leads to increased antibody titres. A third dose of ChAdOx1 nCoV-19 induces antibodies to a level that correlates with high efficacy after second dose and boosts T-cell responses. Funding UK Research and Innovation, Engineering and Physical Sciences Research Council, National Institute for Health Research, Coalition for Epidemic Preparedness Innovations, National Institute for Health Research Oxford Biomedical Research Centre, Chinese Academy of Medical Sciences Innovation Fund for Medical Science, Thames Valley and South Midlands NIHR Clinical Research Network, AstraZeneca, and Wellcome.
- Published
- 2021