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

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

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.

Adolescent, Adult, Antibodies, Neutralizing/immunology, Antibody Formation/immunology, COVID-19/immunology, COVID-19 Vaccines/immunology, Dose-Response Relationship, Drug, Genetic Vectors/immunology, Humans, Immunization, Secondary, Middle Aged, SARS-CoV-2/immunology, Spike Glycoprotein, Coronavirus/immunology, Time Factors, Young Adult
1078-8956
279-288
Barrett, Jordan R
125813b4-dea2-45ee-a8b0-4f586347e9f6
Belij-Rammerstorfer, Sandra
a1f3ac56-807a-4221-9a1f-053fb02470b3
Dold, Christina
2c5f1a88-035f-4eca-8839-4b20b2146b24
Ewer, Katie J
069f04d6-b524-45c7-ad26-ac830b990860
Folegatti, Pedro M
23e5cd74-8076-45e5-9d16-9856641e1e01
Gilbride, Ciaran
a00fd3fe-3978-44cd-85b1-b0ef4a2234fd
Green, Catherine M
74bf353e-9630-408f-9f8e-ec96a54b5771
et al.,
ae4903c5-41d6-4d6f-a17f-317750752b09
Gilbert, Sarah C.
10c23e1c-6e46-4fe8-ae0b-3a1f5cf074f4
Pollard, Andrew J.
f54083f3-c730-4ecb-937e-6fb11fdd6a21
Oxford COVID Vaccine Trial Group
Barrett, Jordan R
125813b4-dea2-45ee-a8b0-4f586347e9f6
Belij-Rammerstorfer, Sandra
a1f3ac56-807a-4221-9a1f-053fb02470b3
Dold, Christina
2c5f1a88-035f-4eca-8839-4b20b2146b24
Ewer, Katie J
069f04d6-b524-45c7-ad26-ac830b990860
Folegatti, Pedro M
23e5cd74-8076-45e5-9d16-9856641e1e01
Gilbride, Ciaran
a00fd3fe-3978-44cd-85b1-b0ef4a2234fd
Green, Catherine M
74bf353e-9630-408f-9f8e-ec96a54b5771
et al.,
ae4903c5-41d6-4d6f-a17f-317750752b09
Gilbert, Sarah C.
10c23e1c-6e46-4fe8-ae0b-3a1f5cf074f4
Pollard, Andrew J.
f54083f3-c730-4ecb-937e-6fb11fdd6a21

Barrett, Jordan R, Belij-Rammerstorfer, Sandra, Dold, Christina, Ewer, Katie J, Folegatti, Pedro M, Gilbride, Ciaran, Green, Catherine M, et al., , Gilbert, Sarah C. and Pollard, Andrew J. , Oxford COVID Vaccine Trial Group (2020) Phase 1/2 trial of SARS-CoV-2 vaccine ChAdOx1 nCoV-19 with a booster dose induces multifunctional antibody responses. Nature Medicine, 27 (2), 279-288. (doi:10.1038/s41591-020-01179-4).

Record type: Article

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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More information

Accepted/In Press date: 16 November 2020
e-pub ahead of print date: 17 December 2020
Additional Information: Acknowledgements The funder had no role in the design, execution or analysis of this study. This report is independent research funded by the National Institute for Health Research (NIHR). The views expressed in this publication are those of the authors and not necessarily those of the NIHR or the UK Department of Health and Social Care (DHSC). Additional resources for study delivery were provided by NIHR Southampton Clinical Research Facility and NIHR Southampton Biomedical Research Centre; University Hospital Southampton NHS Foundation Trust; the NIHR Imperial Clinical Research Facility; and NIHR North West London, South London, Wessex and West of England Local Clinical Research Networks; and NIHR Oxford Health Biomedical Research Centre. P.M.F. received funding from the Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior, Brazil (finance code 001). The control vaccine was provided free of charge by the UK DHSC. The authors are grateful to the volunteers who participated in this study. The investigators express their gratitude for the contribution of all the trial participants, the invaluable advice of the international DSMB (Supplementary Information) and the independent members of the trial steering committee. We are grateful for the advice and intellectual support from K.S. Campbell (Institute for Cancer Research, Philadelphia) with the NK cell line culture and use. The authors are grateful to the senior management at AstraZeneca for facilitating and funding the manufacture of the AZD1222 vaccine candidate, the pseudovirus neutralization assays and Meso Scale antibody assay used in this study. AstraZeneca reviewed the data from the study and the final manuscript before submission, but the authors retained editorial control. Finally, we acknowledge UKRI, NIHR, CEPI, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland’s NIHR Clinical Research Network and AstraZeneca.
Keywords: Adolescent, Adult, Antibodies, Neutralizing/immunology, Antibody Formation/immunology, COVID-19/immunology, COVID-19 Vaccines/immunology, Dose-Response Relationship, Drug, Genetic Vectors/immunology, Humans, Immunization, Secondary, Middle Aged, SARS-CoV-2/immunology, Spike Glycoprotein, Coronavirus/immunology, Time Factors, Young Adult

Identifiers

Local EPrints ID: 450682
URI: http://eprints.soton.ac.uk/id/eprint/450682
ISSN: 1078-8956
PURE UUID: 9ba4c42c-bb9e-49de-a6ff-4469bc67a31a

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Date deposited: 06 Aug 2021 16:31
Last modified: 27 Apr 2022 08:11

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Contributors

Author: Jordan R Barrett
Author: Sandra Belij-Rammerstorfer
Author: Christina Dold
Author: Katie J Ewer
Author: Pedro M Folegatti
Author: Ciaran Gilbride
Author: Catherine M Green
Author: et al.
Author: Sarah C. Gilbert
Author: Andrew J. Pollard
Corporate Author: Oxford COVID Vaccine Trial Group

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