TY - JOUR
AU - Flaxman, Amy
AU - Marchevsky, Natalie G.
AU - Jenkin, Daniel
AU - Aboagye, Jeremy
AU - Aley, Parvinder K.
AU - Angus, Brian
AU - Belij-Rammerstorfer, Sandra
AU - Bibi, Sagida
AU - Bittaye, Mustapha
AU - Cappuccini, Federica
AU - Cicconi, Paola
AU - Clutterbuck, Elizabeth A.
AU - Davies, Sophie
AU - Dejnirattisai, Wanwisa
AU - Dold, Christina
AU - Ewer, Katie J.
AU - Folegatti, Pedro M.
AU - Fowler, Jamie
AU - Hill, Adrian V.S.
AU - Kerridge, Simon
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AU - Mongkolsapaya, Juthathip
AU - Mujadidi, Yama F.
AU - Plested, Emma
AU - Ramasamy, Maheshi N.
AU - Robinson, Hannah
AU - Sanders, Helen
AU - Sheehan, Emma
AU - Smith, Holly
AU - Snape, Matthew D
AU - Song, Rinn
AU - Woods, Danielle
AU - Screaton, Gavin
AU - Gilbert, Sarah C.
AU - Voysey, Merryn
AU - Pollard, Andrew J.
AU - Lambe, Teresa
AU - Adlou, Syed
AU - Aley, Robert
AU - Ali, Aabidah
AU - Anslow, Rachel
AU - Baker, Megan
AU - Baker, Phillip
AU - Barrett, Jordan R.
AU - Bates, Louise
AU - Beadon, Kirsten
AU - Beckley, Rebecca
AU - Bell, Jonathan
AU - Bellamy, Duncan
AU - Beveridge, Amy
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AU - Bridges-Webb, Alice
AU - Brown, Charlie
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AU - Collins, Andrea M.
AU - Cooper, Rachel
AU - Crocker, Wendy E.M.
AU - Darton, Thomas C.
AU - Davies, Hannah
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AU - Demissie, Tesfaye
AU - Di Maso, Claudio
AU - Dinesh, Tanya
AU - Donnellan, Francesca R.
AU - Douglas, Alexander D.
AU - Drake-Brockman, Rachael
AU - Duncan, Christopher J.A.
AU - Elias, Sean C.
AU - Emary, Katherine R.W.
AU - Ghulam Farooq, Mutjaba
AU - Faust, Saul N.
AU - Felle, Sally
AU - Ferreira, Daniela M.
AU - Ferreira Da Silva, Carla
AU - Finn, Adam
AU - Ford, Karen J.
AU - Francis, Emma
AU - Furze, Julie
AU - Fuskova, Michelle
AU - Galiza, Eva
AU - Gibertoni Cruz, Ana
AU - Godfrey, Leila
AU - Goodman, Anna L.
AU - Green, Catherine M.
AU - Green, Christopher A.
AU - Greenwood, Nicola
AU - Harrison, Daisy
AU - Hart, Thomas
AU - Hawkins, Sophia
AU - Heath, Paul T.
AU - Hill, Helen C.
AU - Hillson, Kushalinii
AU - Horsington, Bryn
AU - Hou, Mimi M.
AU - Howe, Elizabeth
AU - Howell, Nicola
AU - Joe, Carina
AU - Jones, Elizabeth
AU - Kasanyinga, Mwila
AU - Keen, Jade
AU - Kelly, Sarah
AU - Kerr, David
AU - Khan, Liaquat
AU - Khozoee, Baktash
AU - Kinch, Jasmin
AU - Kinch, Patrick
AU - Koleva, Stanislava
AU - Kwok, Jonathan
AU - Larkworthy, Colin W.
AU - Lawrie, Alison M.
AU - Lazarus, Rajeka
AU - Lees, Emily A.
AU - Li, Grace
AU - Libri, Vincenzo
AU - Lillie, Patrick J.
AU - Linder, Aline
AU - Long, Fei
AU - Lopez Ramon, Raquel
AU - Mabbett, Reece
AU - Makinson, Rebecca
AU - Marinou, Spyridoula
AU - Marlow, Emma
AU - Marshall, Julia L.
AU - Mazur, Olga
AU - McEwen, Jo
AU - McGregor, Alastair C.
AU - Mokaya, Jolynne
AU - Morey, Ella
AU - Morshead, Gertraud
AU - Morter, Richard
AU - Muller, Jilly
AU - Mweu, Philomena
AU - Noristani, Rabiullah
AU - Owino, Nelly
AU - Polo Peralta Alvarez, Marco
AU - Platt, Abigail
AU - Pollock, Katrina M.
AU - Poulton, Ian
AU - Provstgaard-Morys, Samuel
AU - Pulido-Gomez, David
AU - Rajan, Matthew
AU - Ramos Lopez, Fernando
AU - Ritchie, Adam
AU - Roberts, Hannah
AU - Rollier, Christine
AU - Rudiansyah, Indra
AU - Sanders, Katherine
AU - Saunders, Jack E.
AU - Seddiqi, Samiullah
AU - Sharpe, Hannah R.
AU - Shaw, Robert
AU - Silva-Reyes, Laura
AU - Singh, Nisha
AU - Smith, David J.
AU - Smith, Catherine C.
AU - Smith, Andrew
AU - Spencer, Alexandra J.
AU - Stuart, Arabella S.V.
AU - Sutherland, Rebecca
AU - Szigeti, Anna
AU - Tang, Karly
AU - Thomas, Merin
AU - Thomas, Tonia M.
AU - Thompson, Amber
AU - Thomson, Emma C.
AU - Török, Estée M.
AU - Toshner, Mark
AU - Tran, Nguyen
AU - Trivett, Rose
AU - Turnbull, Iain
AU - Turner, Cheryl
AU - Turner, David P.J.
AU - Ulaszewska, Marta
AU - Vichos, Iason
AU - Walker, Laura
AU - Watson, Marion E. E.
AU - Whelan, Conor
AU - White, Rachel
AU - Williams, Sarah J.
AU - Williams, Christopher J.A.
AU - Wright, Daniel
AU - Yao, Andy
PY - 2021
DA - September
TI - 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)
JO - Lancet
EP - 990
VL - 398
IS - 10304
DO - http://dx.doi.org/10.1016/S0140-6736(21)01699-8
AB - 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.
PB - Elsevier
UR - http://eprints.gla.ac.uk/260578/
KW - Coronavirus (COVID-19)
ER