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Cited by 1,324SARS-CoV-2 and COVID-19 ResearchCOVID-19 Clinical Research StudiesImmune responses and vaccinations

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

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Ramasamy, Maheshi N, Minassian, Angela M, Ewer, Katie J, Flaxman, Amy L, Folegatti, Pedro M, Owens, Daniel R, Voysey, Merryn, Aley, Parvinder K +413 more·2020·The Lancet
DOI 10.1016/s0140-6736(20)32466-1PMC PMC7674972
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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 (AZD1222), 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 × 10 10 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 × 10 10 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 (MNA 80 ). 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

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  1. [2]Wu Z McGoogan JM Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases From the Chinese Center for Disease Control and Prevention JAMA 323 2020 1239 1242 32091533
  2. [10]Walsh EE Frenck RW Jr Falsey AR Safety and immunogenicity of two RNA-based COVID-19 vaccine candidates N Engl J Med 2020 published online Oct 14. 10.1056/NEJMoa2027906 PMC7583697 33053279 · DOI · Paper page
  3. [14]Xia S Duan K Zhang Y Effect of an inactivated vaccine against SARS-CoV-2 on safety and immunogenicity outcomes: interim analysis of 2 randomized clinical trials JAMA 324 2020 951 960 32789505 PMC7426884
  4. [23]Tapia MD Sow SO Mbaye KD Safety, reactogenicity, and immunogenicity of a chimpanzee adenovirus vectored Ebola vaccine in children in Africa: a randomised, observer-blind, placebo-controlled, phase 2 trial Lancet Infect Dis 20 2020 719 730 32199492

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Ramasamy, M. N., Minassian, A. M., Ewer, K. J., Flaxman, A. L., Folegatti, P. M., Owens, D. R., Voysey, M., Aley, P. K., Angus, B., Babbage, G., Belij-Rammerstorfer, S., Berry, L., Bibi, S., Bittaye, M., Cathie, K., Chappell, H., Charlton, S., Cicconi, P., Clutterbuck, E. A., Colin-Jones, R., Dold, C., Emary, K. R. W., Fedosyuk, S., Fuskova, M., Gbesemete, D., Green, C., Hallis, B., Hou, M. M., Jenkin, D., Joe, C. C. D., Kelly, E. J., Kerridge, S., Lawrie, A. M., Lelliott, A., Lwin, M. N., Makinson, R., Marchevsky, N. G., Mujadidi, Y., Munro, A. P. S., Pacurar, M., Plested, E., Rand, J., Rawlinson, T., Rhead, S., Robinson, H., Ritchie, A. J., Ross-Russell, A. L., Saich, S., Singh, N., Smith, C. C., Snape, M. D., Song, R., Tarrant, R., Themistocleous, Y., Thomas, K. M., Villafana, T. L., Warren, S. C., Watson, M. E. E., Douglas, A. D., Hill, A. V. S., Lambe, T., Gilbert, S. C., Faust, S. N., Pollard, A. J., Aboagye, J., Adams, K., Ali, A., Allen, E. R., Allen, L., Allison, J. L., Andritsou, F., Anslow, R., Arbe-Barnes, E. H., Baker, M., Baker, N., Baker, P., Baleanu, I., Barker, D., Barnes, E., Barrett, J. R., Barrett, K., Bates, L., Batten, A., Beadon, K., Beckley, R., Bellamy, D., Berg, A., Bermejo, L., Berrie, E., Beveridge, A., Bewley, K., Bijker, E. M., Birch, G., Blackwell, L., Bletchly, H., Blundell, C. L., Blundell, S. R., Bolam, E., Boland, E., Bormans, D., Borthwick, N., Boukas, K., Bower, T., Bowring, F., Boyd, A., Brenner, T., Brown, P., Brown-O'Sullivan, C., Bruce, S., Brunt, E., Burbage, J., Burgoyne, J., Buttigieg, K. R., Byard, N., Cabera Puig, I., Camara, S., Cao, M., Cappuccini, F., Carr, M., Carroll, M. W., Cashen, P., Cavey, A., Chadwick, J., Challis, R., Chapman, D., Charles, D., Chelysheva, I., Cho, J.-S., Cifuentes, L., Clark, E., Collins, S., Conlon, C. P., Coombes, N. S., Cooper, R., Cooper, C., Crocker, W. E. M., Crosbie, S., Cullen, D., Cunningham, C., Cuthbertson, F., Datoo, B. E., Dando, L., Datoo, M. S., Datta, C., Davies, H., Davies, S., Davis, E. J., Davis, J., Dearlove, D., Demissie, T., Di Marco, S., Di Maso, C., DiTirro, D., Docksey, C., Dong, T., Donnellan, F. R., Douglas, N., Downing, C., Drake, J., Drake-Brockman, R., Drury, R. E., Dunachie, S. J., Edwards, C. J., Edwards, N. J., El Muhanna, O., Elias, S. C., Elliott, R. S., Elmore, M. J., English, M. R., Felle, S., Feng, S., Ferreira Da Silva, C., Field, S., Fisher, R., Fixmer, C., Ford, K. J., Fowler, J., Francis, E., Frater, J., Furze, J., Galian-Rubio, P., Galloway, C., Garlant, H., Gavrila, M., Gibbons, F., Gibbons, K., Gilbride, C., Gill, H., Godwin, K., Gordon-Quayle, K., Gorini, G., Goulston, L., Grabau, C., Gracie, L., Graham, N., Greenwood, N., Griffiths, O., Gupta, G., Hamilton, E., Hanumunthadu, B., Harris, S. A., Harris, T., Harrison, D., Hart, T. C., Hartnell, B., Haskell, L., Hawkins, S., Henry, J. A., Hermosin Herrera, M., Hill, D., Hill, J., Hodges, G., Hodgson, S. H. C., Horton, K. L., Howe, E., Howell, N., Howes, J., Huang, B., Humphreys, J., Humphries, H. E., Iveson, P., Jackson, F., Jackson, S., Jauregui, S., Jeffers, H., Jones, B., Jones, C. E., Jones, E., Jones, K., Joshi, A., Kailath, R., Keen, J., Kelly, D. M., Kelly, S., Kelly, D., Kerr, D., Khan, L., Khozoee, B., Killen, A., Kinch, J., King, L. D. W., King, T. B., Kingham, L., Klenerman, P., Knight, J. C., Knott, D., Koleva, S., Lang, G., Larkworthy, C. W., Larwood, J. P. J., Law, R., Lee, A., Lee, K. Y. N., Lees, E. A., Leung, S., Li, Y., Lias, A. M., Linder, A., Lipworth, S., Liu, S., Liu, X., Lloyd, S., Loew, L., Lopez Ramon, R., Madhavan, M., Mainwaring, D. O., Mallett, G., Mansatta, K., Marinou, S., Marius, P., Marlow, E., Marriott, P., Marshall, J. L., Martin, J., Masters, S., McEwan, J., McGlashan, J. L., McInroy, L., McRobert, N., Megson, C., Mentzer, A. J., Mirtorabi, N., Mitton, C., Moore, M., Moran, M., Morey, E., Morgans, R., Morris, S. J., Morrison, H. M., Morshead, G., Morter, R., Moya, N. A., Mukhopadhyay, E., Muller, J., Munro, C., Murphy, S., Mweu, P., Noé, A., Nugent, F. L., O'Brien, K., O'Connor, D., Oguti, B., Olchawski, V., Oliveira, C., O'Reilly, P. J., Osborne, P., Owen, L., Owino, N., Papageorgiou, P., Parracho, H., Parsons, K., Patel, B., Patrick-Smith, M., Peng, Y., Penn, E. J., Peralta-Alvarez, M. P., Perring, J., Petropoulos, C., Phillips, D. J., Pipini, D., Pollard, S., Poulton, I., Pratt, D., Presland, L., Proud, P. C., Provstgaard-Morys, S., Pueschel, S., Pulido, D., Rabara, R., Radia, K., Rajapaska, D., Ramos Lopez, F., Ratcliffe, H., Rayhan, S., Rees, B., Reyes Pabon, E., Roberts, H., Robertson, I., Roche, S., Rollier, C. S., Romani, R., Rose, Z., Rudiansyah, I., Sabheha, S., Salvador, S., Sanders, H., Sanders, K., Satti, I., Sayce, C., Schmid, A. B., Schofield, E., Screaton, G., Sedik, C., Seddiqi, S., Segireddy, R. R., Selby, B., Shaik, I., Sharpe, H. R., Shaw, R., Shea, A., Silk, S., Silva-Reyes, L., Skelly, D. T., Smith, D. J., Smith, D. C., Smith, N., Spencer, A. J., Spoors, L., Stafford, E., Stamford, I., Stockdale, L., Stockley, D., Stockwell, L. V., Stokes, M., Strickland, L. H., Stuart, A., Sulaiman, S., Summerton, E., Swash, Z., Szigeti, A., Tahiri-Alaoui, A., Tanner, R., Taylor, I., Taylor, K., Taylor, U., te Water Naude, R., Themistocleous, A., Thomas, M., Thomas, T. M., Thompson, A., Thompson, K., Thornton-Jones, V., Tinh, L., Tomic, A., Tonks, S., Towner, J., Tran, N., Tree, J. A., Truby, A., Turner, C., Turner, R., Ulaszewska, M., Varughese, R., Verbart, D., Verheul, M. K., Vichos, I., Walker, L., Wand, M. E., Watkins, B., Welch, J., West, A. J., White, C., White, R., Williams, P., Woodyer, M., Worth, A. T., Wright, D., Wrin, T., Yao, X. L., Zbarcea, D.-A., & Zizi, D.
Affiliations
  • University of Oxford (GB)
  • University Hospital Southampton NHS Foundation Trust (GB)
  • University of Southampton (GB)
  • Public Health England (GB)
  • AstraZeneca (United States) (US)
  • Boston Children's Hospital (US)
  • NIHR Oxford Biomedical Research Centre (GB)
Corresponding author
Ramasamy, Maheshi N
ORCID
Venue
The Lancet
Publisher
Elsevier BV
Published
2020-12
Volume
396
Issue
10267
Pages
1979-1993
ISSN
  • 0099-5355 (ISSN-L)
  • 0140-6736
DOI
10.1016/s0140-6736(20)32466-1
PMC
PMC7674972
OpenAlex
W3104989674
Cited by
1,324
References
20
Citations by year
2026: 23 · 2025: 61 · 2024: 87 · 2023: 184 · 2022: 404 · 2021: 544 · 2020: 20
FWCI
37.82
Type
journal article
Language
en
Update notices
Open access
Licence
Locations
  • The Lancet (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
  • ePrints Soton (University of Southampton) (acceptedVersion)
  • Open Research (University of Surrey) (submittedVersion, cc-by)
  • Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by-nc-nd)
Funders
  • National Institute for Health Research
  • Coalition for Epidemic Preparedness Innovations
  • UK Research and Innovation
Topics
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
  • Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
  • Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
Keywords
ChAdOx1 nCoV-19 vaccine, AZD1222, COVID-19 vaccines, chimpanzee adenovirus vector, prime-boost regimen, immunogenicity, vaccine safety, older adults, immunosenescence, SARS-CoV-2, low-dose vaccine, SARS-CoV-2 spike protein
MeSH terms
Immunogenicity, Vaccine, COVID-19, SARS-CoV-2, COVID-19 Vaccines, ChAdOx1 nCoV-19, Adolescent, Adult, Age Factors, Aged, Aged, 80 and over, Female, Humans, Immunoglobulin G, Immunization, Secondary, Male, Middle Aged, Single-Blind Method, Young Adult

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