The ChAdOx1 vectored vaccine, AZD2816, induces strong immunogenicity against SARS-CoV-2 beta (B.1.351) and other variants of concern in preclinical studies.


Journal

EBioMedicine
ISSN: 2352-3964
Titre abrégé: EBioMedicine
Pays: Netherlands
ID NLM: 101647039

Informations de publication

Date de publication:
Mar 2022
Historique:
received: 07 09 2021
revised: 07 02 2022
accepted: 10 02 2022
pubmed: 2 3 2022
medline: 5 4 2022
entrez: 1 3 2022
Statut: ppublish

Résumé

There is an ongoing global effort to design, manufacture, and clinically assess vaccines against SARS-CoV-2. Over the course of the ongoing pandemic a number of new SARS-CoV-2 virus isolates or variants of concern (VoC) have been identified containing mutations in key proteins. In this study we describe the generation and preclinical assessment of a ChAdOx1-vectored vaccine (AZD2816) which expresses the spike protein of the Beta VoC (B.1.351). We demonstrate that AZD2816 is immunogenic after a single dose. When AZD2816 is used as a booster dose in animals primed with a vaccine encoding the original spike protein (ChAdOx1 nCoV-19/ [AZD1222]), an increase in binding and neutralising antibodies against Beta (B.1.351), Gamma (P.1) and Delta (B.1.617.2) is observed following each additional dose. In addition, a strong and polyfunctional T cell response was measured all booster regimens. Real world data is demonstrating that one or more doses of licensed SARS-CoV-2 vaccines confer reduced protection against hospitalisation and deaths caused by divergent VoC, including Omicron. Our data support the ongoing clinical development and testing of booster vaccines to increase immunity against highly mutated VoC. This research was funded by AstraZeneca with supporting funds from MRC and BBSRC.

Sections du résumé

BACKGROUND BACKGROUND
There is an ongoing global effort to design, manufacture, and clinically assess vaccines against SARS-CoV-2. Over the course of the ongoing pandemic a number of new SARS-CoV-2 virus isolates or variants of concern (VoC) have been identified containing mutations in key proteins.
METHODS METHODS
In this study we describe the generation and preclinical assessment of a ChAdOx1-vectored vaccine (AZD2816) which expresses the spike protein of the Beta VoC (B.1.351).
FINDINGS RESULTS
We demonstrate that AZD2816 is immunogenic after a single dose. When AZD2816 is used as a booster dose in animals primed with a vaccine encoding the original spike protein (ChAdOx1 nCoV-19/ [AZD1222]), an increase in binding and neutralising antibodies against Beta (B.1.351), Gamma (P.1) and Delta (B.1.617.2) is observed following each additional dose. In addition, a strong and polyfunctional T cell response was measured all booster regimens.
INTERPRETATION CONCLUSIONS
Real world data is demonstrating that one or more doses of licensed SARS-CoV-2 vaccines confer reduced protection against hospitalisation and deaths caused by divergent VoC, including Omicron. Our data support the ongoing clinical development and testing of booster vaccines to increase immunity against highly mutated VoC.
FUNDING BACKGROUND
This research was funded by AstraZeneca with supporting funds from MRC and BBSRC.

Identifiants

pubmed: 35228013
pii: S2352-3964(22)00086-X
doi: 10.1016/j.ebiom.2022.103902
pmc: PMC8881183
pii:
doi:

Substances chimiques

COVID-19 Vaccines 0
ChAdOx1 nCoV-19 B5S3K2V0G8

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

103902

Subventions

Organisme : Biotechnology and Biological Sciences Research Council
ID : BBS/E/I/00007039
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BBS/E/I/00007038
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BBS/E/I/00007034
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_19055
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BBS/E/I/COV07001
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/W005611/1
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BBS/E/I/00007031
Pays : United Kingdom

Informations de copyright

Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests SCG is co-founder and board member of Vaccitech and named as an inventor on a patent covering use of ChAdOx1-vectored vaccines and a patent application covering the ChAdOx1 nCoV-19 (AZD1222) vaccine. TL is named as an inventor on a patent application covering the ChAdOx1 nCoV-19 (AZD1222) vaccine and was consultant to Vaccitech. PM was an employee of AstraZeneca, KR is an employee of AstraZeneca. HB was an employee of AstraZeneca and is a named inventor on a patent application covering the AZD2816 vaccine.

Auteurs

Alexandra J Spencer (AJ)

Nuffield Department of Medicine, The Jenner Institute, University of Oxford, ORCRB, Roosevelt Drive, Oxford OX3 7DQ, United Kingdom. Electronic address: alex.spencer@ndm.ox.ac.uk.

Susan Morris (S)

Nuffield Department of Medicine, The Jenner Institute, University of Oxford, ORCRB, Roosevelt Drive, Oxford OX3 7DQ, United Kingdom.

Marta Ulaszewska (M)

Nuffield Department of Medicine, The Jenner Institute, University of Oxford, ORCRB, Roosevelt Drive, Oxford OX3 7DQ, United Kingdom.

Claire Powers (C)

Nuffield Department of Medicine, The Jenner Institute, University of Oxford, ORCRB, Roosevelt Drive, Oxford OX3 7DQ, United Kingdom.

Reshma Kailath (R)

Nuffield Department of Medicine, The Jenner Institute, University of Oxford, ORCRB, Roosevelt Drive, Oxford OX3 7DQ, United Kingdom.

Cameron Bissett (C)

Nuffield Department of Medicine, The Jenner Institute, University of Oxford, ORCRB, Roosevelt Drive, Oxford OX3 7DQ, United Kingdom.

Adam Truby (A)

Nuffield Department of Medicine, The Jenner Institute, University of Oxford, ORCRB, Roosevelt Drive, Oxford OX3 7DQ, United Kingdom.

Nazia Thakur (N)

Nuffield Department of Medicine, The Jenner Institute, University of Oxford, ORCRB, Roosevelt Drive, Oxford OX3 7DQ, United Kingdom; The Pirbright Institute, Woking, Surrey, United Kingdom.

Joseph Newman (J)

The Pirbright Institute, Woking, Surrey, United Kingdom.

Elizabeth R Allen (ER)

Nuffield Department of Medicine, The Jenner Institute, University of Oxford, ORCRB, Roosevelt Drive, Oxford OX3 7DQ, United Kingdom.

Indra Rudiansyah (I)

Nuffield Department of Medicine, The Jenner Institute, University of Oxford, ORCRB, Roosevelt Drive, Oxford OX3 7DQ, United Kingdom.

Chang Liu (C)

The Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, United Kingdom; Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, United Kingdom.

Wanwisa Dejnirattisai (W)

The Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, United Kingdom.

Juthathip Mongkolsapaya (J)

The Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, United Kingdom.

Hannah Davies (H)

Nuffield Department of Medicine, The Jenner Institute, University of Oxford, ORCRB, Roosevelt Drive, Oxford OX3 7DQ, United Kingdom.

Francesca R Donnellan (FR)

Nuffield Department of Medicine, The Jenner Institute, University of Oxford, ORCRB, Roosevelt Drive, Oxford OX3 7DQ, United Kingdom.

David Pulido (D)

Nuffield Department of Medicine, The Jenner Institute, University of Oxford, ORCRB, Roosevelt Drive, Oxford OX3 7DQ, United Kingdom.

Thomas P Peacock (TP)

Department of Infectious Disease, Imperial College London, United Kingdom.

Wendy S Barclay (WS)

Department of Infectious Disease, Imperial College London, United Kingdom.

Helen Bright (H)

Virology and Vaccine Discovery, Microbial Sciences, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD United States.

Kuishu Ren (K)

Virology and Vaccine Discovery, Microbial Sciences, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD United States.

Gavin Screaton (G)

The Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, United Kingdom.

Patrick McTamney (P)

Virology and Vaccine Discovery, Microbial Sciences, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD United States.

Dalan Bailey (D)

The Pirbright Institute, Woking, Surrey, United Kingdom.

Sarah C Gilbert (SC)

Nuffield Department of Medicine, The Jenner Institute, University of Oxford, ORCRB, Roosevelt Drive, Oxford OX3 7DQ, United Kingdom.

Teresa Lambe (T)

Nuffield Department of Medicine, The Jenner Institute, University of Oxford, ORCRB, Roosevelt Drive, Oxford OX3 7DQ, United Kingdom; Chinese Academy of Medical Science (CAMS) Oxford Institute (COI), University of Oxford, United Kingdom.

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Classifications MeSH