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Cited by 315SARS-CoV-2 and COVID-19 ResearchAnimal Virus Infections StudiesCOVID-19 Clinical Research Studies

Phase 1/2 trial of SARS-CoV-2 vaccine ChAdOx1 nCoV-19 with a booster dose induces multifunctional antibody responses

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Barrett, Jordan R., Belij-Rammerstorfer, Sandra, Dold, Christina, Ewer, Katie J., Folegatti, Pedro M., Gilbride, Ciaran, Halkerston, Rachel, Hill, Jennifer +295 more·2021·Nature Medicine
DOI 10.1038/s41591-020-01179-4
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Abstract

More than 190 vaccines are currently in development to prevent infection by the novel severe acute respiratory syndrome coronavirus 2. Animal studies suggest that while neutralizing antibodies against the viral spike protein may correlate with protection, additional antibody functions may also be important in preventing infection. Previously, we reported early immunogenicity and safety outcomes of a viral vector coronavirus vaccine, ChAdOx1 nCoV-19 (AZD1222), in a single-blinded phase 1/2 randomized controlled trial of healthy adults aged 18-55 years ( NCT04324606 ). Now we describe safety and exploratory humoral and cellular immunogenicity of the vaccine, from subgroups of volunteers in that trial, who were subsequently allocated to receive a homologous full-dose (SD/SD D56; n = 20) or half-dose (SD/LD D56; n = 32) ChAdOx1 booster vaccine 56 d following prime vaccination. Previously reported immunogenicity data from the open-label 28-d interval prime-boost group (SD/SD D28; n = 10) are also presented to facilitate comparison. Additionally, we describe volunteers boosted with the comparator vaccine (MenACWY; n = 10). In this interim report, we demonstrate that a booster dose of ChAdOx1 nCoV-19 is safe and better tolerated than priming doses. Using a systems serology approach we also demonstrate that anti-spike neutralizing antibody titers, as well as Fc-mediated functional antibody responses, including antibody-dependent neutrophil/monocyte phagocytosis, complement activation and natural killer cell activation, are substantially enhanced by a booster dose of vaccine. A booster dose of vaccine induced stronger antibody responses than a dose-sparing half-dose boost, although the magnitude of T cell responses did not increase with either boost dose. These data support the two-dose vaccine regime that is now being evaluated in phase 3 clinical trials.

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References 58 · Cited by 315

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Authors
Barrett, J. R., Belij-Rammerstorfer, S., Dold, C., Ewer, K. J., Folegatti, P. M., Gilbride, C., Halkerston, R., Hill, J., Jenkin, D., Stockdale, L., Verheul, M. K., Aley, P. K., Angus, B., Bellamy, D., Berrie, E., Bibi, S., Bittaye, M., Carroll, M. W., Cavell, B., Clutterbuck, E. A., Edwards, N., Flaxman, A., Fuskova, M., Gorringe, A., Hallis, B., Kerridge, S., Lawrie, A. M., Linder, A., Liu, X., Madhavan, M., Makinson, R., Mellors, J., Minassian, A., Moore, M., Mujadidi, Y., Plested, E., Poulton, I., Ramasamy, M. N., Robinson, H., Rollier, C. S., Song, R., Snape, M. D., Tarrant, R., Taylor, S., Thomas, K. M., Voysey, M., Watson, M. E. E., Wright, D., Douglas, A. D., Green, C. M., Hill, A. V. S., Lambe, T., Gilbert, S., Pollard, A. J., the Oxford COVID Vaccine Trial Group, Aboagye, J., Alderson, J., Ali, A., Allen, E., Allen, L., Anslow, R., Arancibia-Cárcamo, C. V., Arbe-Barnes, E. H., Baker, M., Baker, P., Baker, N., Baleanu, I., Barnes, E., Bates, L., Batten, A., Beadon, K., Beckley, R., Beveridge, A., Bewley, K. R., Bijker, E. M., Blackwell, L., Blundell, C. L., Bolam, E., Boland, E., Borthwick, N., Boyd, A., Brenner, T., Brown, P., Brown-O’Sullivan, C., Brunt, E., Burbage, J., Buttigieg, K. R., Byard, N., Cabrera Puig, I., Camara, S., Cao, M., Cappuccini, F., Carr, M., Carroll, M. W., Chadwick, J., Chelysheva, I., Cho, J.-S., Cifuentes, L., Clark, E., Colin-Jones, R., Conlon, C. P., Coombes, N. S., Cooper, R., Crocker, W. E. M., Cunningham, C. J., Damratoski, B. E., Datoo, M. S., Datta, C., Davies, H., Demissie, T., Di Maso, C., DiTirro, D., Dong, T., Donnellan, F. R., Douglas, N., Downing, C., Drake, J., Drake-Brockman, R., Drury, R. E., Dunachie, S. J., Muhanna, O. E., Elias, S. C., Elmore, M. J., Emary, K. R. W., English, M. R., Felle, S., Feng, S., Da Silva, C. F., Field, S., Fisher, R., Ford, K. J., Fowler, J., Francis, E., Frater, J., Furze, J., Galian-Rubio, P., Garlant, H., Godwin, K., Gorini, G., Gracie, L., Gupta, G., Hamilton, E., Hamlyn, J., Hanumunthadu, B., Harris, S. A., Harrison, D., Hart, T. C., Hawkins, S., Henry, J. A., Hodges, G., Hodgson, S. H. C., Hou, M. M., Howe, E., Howell, N., Huang, B., Humphries, H., Iveson, P., Jackson, S., Jackson, F., Jauregui, S., Jeffery, K., Jones, E., Jones, K., Kailath, R., Keen, J., Kelly, S., Kelly, D., Kelly, E., Kerr, D., Khan, L., Khozoee, B., Killen, A., Kinch, J., King, T. B., King, L., Kingham-Page, L., Klenerman, P., Knight, J. C., Knott, D., Koleva, S., Larkworthy, C. W., Larwood, J. P. J., Lees, E. A., Lelliott, A., Leung, S., Li, Y., Lias, A. M., Lipworth, S., Liu, S., Loew, L., Lopez Ramon, R., Mallett, G., Mansatta, K., Marchevsky, N. G., Marinou, S., Marlow, E., Marshall, J. L., Matthews, P., McEwan, J., McGlashan, J., McInroy, L., Meddaugh, G., Mentzer, A. J., Mirtorabi, N., Morey, E., Morgans, R., Morris, S. J., Morrison, H., Morshead, G., Morter, R., Moya, N., Mukhopadhyay, E., Muller, J., Munro, C., Murphy, S., Mweu, P., Noé, A., Nugent, F. L., Nuthall, E., O’Brien, K., O’Connor, D., O’Donnell, D., Oguti, B., Olchawski, V., Oliveria, C., O’Reilly, P. J., Osborne, P., Owino, N., Parker, K., Parracho, H., Patrick-Smith, M., Peng, Y., Penn, E., Peralta Alvarez, M. P., Perring, J., Petropoulos, C., Pfafferott, K., Pipini, D., Phillips, D., Proud, P., Provstgaard-Morys, S., Pulido, D., Radia, K., Rajapaksa, D., Ramos Lopez, F., Ratcliffe, H., Rawlinson, T., Pabon, E. R., Rhead, S., Ritchie, A. J., Roberts, H., Roche, S., Rudiansyah, I., Salvador, S., Sanders, H., Sanders, K., Satti, I., Schmid, A., Schofield, E., Screaton, G., Sedik, C., Shaik, I., Sharpe, H. R., Shea, A., Silk, S., Silva-Reyes, L., Skelly, D. T., Smith, C. C., Smith, D. J., Spencer, A. J., Stafford, E., Szigeti, A., Tahiri-Alaoui, A., Tanner, R., Taylor, I. J., Taylor, K., te Water Naude, R., Themistocleous, Y., Themistocleous, A., Thomas, M., Thomas, T. M., Thompson, A., Tinh, L., Tomic, A., Tonks, S., Towner, J., Tran, N., Tree, J. A., Truby, A., Turner, C., Turner, N., Ulaszewska, M., Varughese, R., Vichos, I., Walker, L., Wand, M., White, C., White, R., Williams, P., Worth, A. T., Wrin, T., Yao, X. L., & Zizi, D.
Affiliations
  • University of Oxford (GB)
  • Public Health England (GB)
  • LabCorp (United States) (US)
  • Centre for Human Genetics (GB)
Corresponding author
  • Jenkin, Daniel
  • Pollard, Andrew J.
ORCID
Venue
Nature Medicine
Publisher
Springer Science and Business Media LLC
Published
2020-12-17
Volume
27
Issue
2
Pages
279-288
ISSN
  • 1078-8956 (ISSN-L)
  • 1546-170X
DOI
10.1038/s41591-020-01179-4
OpenAlex
W3111128314
Cited by
315
References
58
Citations by year
2026: 10 · 2025: 18 · 2024: 27 · 2023: 51 · 2022: 99 · 2021: 108 · 2020: 2
FWCI
8.54
Type
journal article
Language
en
Update notices
correction (2021-05-06)
Open access
Licence
Locations
  • Nature Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • Open Research (University of Surrey) (submittedVersion, cc-by)
  • ePrints Soton (University of Southampton) (submittedVersion)
Funders
  • AstraZeneca
  • University of Pennsylvania
  • Wellcome Trust (110,110z/15/Z, 095541/A/11/Z, 109965/Z/15/Z)
  • University Hospital Southampton NHS Foundation Trust
  • UK Research and Innovation
  • Coalition for Epidemic Preparedness Innovations
  • National Institute for Health and Care Research (CL-2018-13-007, CL-2016-13-008, NIHR202437, ACF-2018-13-005, NIHR300791, NF-SI-0515-10005, COV19OxfordVaccine01, NF-SI-0617-10139)
  • Department of Health and Social Care
  • Academy of Medical Sciences (SGL023\1089)
  • University of Oxford
  • Public Health England
  • Chinese Academy of Medical Sciences
  • Oxford University Hospitals NHS Foundation Trust
  • National Institute for Health Research Southampton Biomedical Research Centre
  • Medical Research Council (MR/L006588/1, MR/T001151/1, MC_UU_00008/11, MR/L018942/1)
  • Engineering and Physical Sciences Research Council (EP/R013756/1)
  • NIHR Oxford Biomedical Research Centre
Topics
  • Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
  • Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
  • Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
Keywords
ChAdOx1 nCoV-19 vaccine, AZD1222, COVID-19 vaccines, booster vaccination, viral vector vaccines, humoral immunogenicity, antibody-dependent phagocytosis, complement activation, NK cell activation, T cell response, vaccine safety
MeSH terms
COVID-19, SARS-CoV-2, COVID-19 Vaccines, ChAdOx1 nCoV-19, Adolescent, Adult, Antibody Formation, Dose-Response Relationship, Drug, Genetic Vectors, Humans, Immunization, Secondary, Middle Aged, Time Factors, Young Adult, Antibodies, Neutralizing, Spike Glycoprotein, Coronavirus

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