The ChAdOx1 vectored vaccine, AZD2816, induces strong immunogenicity against SARS-CoV-2 beta (B.1.351) and other variants of concern in preclinical studies
Alexandra J Spencer,
Susan Morris,
Marta Ulaszewska,
Claire Powers,
Reshma Kailath,
Cameron Bissett,
Adam Truby,
Nazia Thakur,
Joseph Newman,
Elizabeth R Allen,
Indra Rudiansyah,
Chang Liu,
Wanwisa Dejnirattisai,
Juthathip Mongkolsapaya,
Hannah Davies,
Francesca R Donnellan,
David Pulido,
Thomas P. Peacock,
Wendy S. Barclay,
Helen Bright,
Kuishu Ren,
Gavin Screaton,
Patrick McTamney,
Dalan Bailey,
Sarah C Gilbert,
Teresa Lambe
Affiliations
Alexandra J Spencer
Nuffield Department of Medicine, The Jenner Institute, University of Oxford, ORCRB, Roosevelt Drive, Oxford OX3 7DQ, United Kingdom; Corresponding author.
Susan Morris
Nuffield Department of Medicine, The Jenner Institute, University of Oxford, ORCRB, Roosevelt Drive, Oxford OX3 7DQ, United Kingdom
Marta Ulaszewska
Nuffield Department of Medicine, The Jenner Institute, University of Oxford, ORCRB, Roosevelt Drive, Oxford OX3 7DQ, United Kingdom
Claire Powers
Nuffield Department of Medicine, The Jenner Institute, University of Oxford, ORCRB, Roosevelt Drive, Oxford OX3 7DQ, United Kingdom
Reshma Kailath
Nuffield Department of Medicine, The Jenner Institute, University of Oxford, ORCRB, Roosevelt Drive, Oxford OX3 7DQ, United Kingdom
Cameron Bissett
Nuffield Department of Medicine, The Jenner Institute, University of Oxford, ORCRB, Roosevelt Drive, Oxford OX3 7DQ, United Kingdom
Adam Truby
Nuffield Department of Medicine, The Jenner Institute, University of Oxford, ORCRB, Roosevelt Drive, Oxford OX3 7DQ, United Kingdom
Nazia Thakur
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
The Pirbright Institute, Woking, Surrey, United Kingdom
Elizabeth R Allen
Nuffield Department of Medicine, The Jenner Institute, University of Oxford, ORCRB, Roosevelt Drive, Oxford OX3 7DQ, United Kingdom
Indra Rudiansyah
Nuffield Department of Medicine, The Jenner Institute, University of Oxford, ORCRB, Roosevelt Drive, Oxford OX3 7DQ, United Kingdom
Chang Liu
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
The Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, United Kingdom
Juthathip Mongkolsapaya
The Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, United Kingdom
Hannah Davies
Nuffield Department of Medicine, The Jenner Institute, University of Oxford, ORCRB, Roosevelt Drive, Oxford OX3 7DQ, United Kingdom
Francesca R Donnellan
Nuffield Department of Medicine, The Jenner Institute, University of Oxford, ORCRB, Roosevelt Drive, Oxford OX3 7DQ, United Kingdom
David Pulido
Nuffield Department of Medicine, The Jenner Institute, University of Oxford, ORCRB, Roosevelt Drive, Oxford OX3 7DQ, United Kingdom
Thomas P. Peacock
Department of Infectious Disease, Imperial College London, United Kingdom
Wendy S. Barclay
Department of Infectious Disease, Imperial College London, United Kingdom
Helen Bright
Virology and Vaccine Discovery, Microbial Sciences, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD United States
Kuishu Ren
Virology and Vaccine Discovery, Microbial Sciences, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD United States
Gavin Screaton
The Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, United Kingdom
Patrick McTamney
Virology and Vaccine Discovery, Microbial Sciences, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD United States
Dalan Bailey
The Pirbright Institute, Woking, Surrey, United Kingdom
Sarah C Gilbert
Nuffield Department of Medicine, The Jenner Institute, University of Oxford, ORCRB, Roosevelt Drive, Oxford OX3 7DQ, United Kingdom
Teresa Lambe
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
Summary: 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: 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: 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: 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: This research was funded by AstraZeneca with supporting funds from MRC and BBSRC.
