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Tolerability and Immunogenicity After a Late Second Dose or a Third Dose of ChAdOx1 nCoV-19 (AZD1222)

35 Pages Posted: 28 Jun 2021

See all articles by Amy Flaxman

Amy Flaxman

University of Oxford - The Jenner Institute

Natalie Marchevsky

University of Oxford - Oxford Vaccine Group

Daniel Jenkin

University of Oxford - The Jenner Institute

Jeremy Aboagye

University of Oxford - The Jenner Institute

Parvinder K. Aley

University of Oxford - Oxford Vaccine Group

Brian John Angus

University of Oxford - The Jenner Institute; University of Oxford - Oxford Vaccine Group

Sandra Belij-Rammerstorfer

University of Oxford - The Jenner Institute

Sagida Bibi

University of Oxford - Oxford Vaccine Group

Mustapha Bittaye

University of Oxford - The Jenner Institute

Federica Cappuccini

University of Oxford - The Jenner Institute

Paola Cicconi

University of Oxford - The Jenner Institute; University of Oxford - Oxford Vaccine Group

Elizabeth Clutterbuck

University of Oxford - Oxford Vaccine Group

Sophie Davies

University of Oxford - The Jenner Institute

Wanwisa Dejnirattisai

University of Oxford - Wellcome Centre for Human Genetics

Christina Dold

University of Oxford - Oxford Vaccine Group

Katie Ewer

University of Oxford - The Jenner Institute

Pedro M. Folegatti

University of Oxford - The Jenner Institute

Jamie Fowler

University of Oxford - The Jenner Institute

Adrian V. S. Hill

University of Oxford - The Jenner Institute; University of Oxford - Wellcome Trust Centre for Human Genetics; University of Oxford - Centre for Clinical Vaccinology and Tropical Medicine

Simon Kerridge

University of Oxford - Oxford Vaccine Group

Angela M. Minassian

University of Oxford - The Jenner Institute

Juthathip Mongkolspaya

University of Oxford - Wellcome Centre for Human Genetics

Yama Farooq Mujadidi

University of Oxford - Oxford Vaccine Group

Emma Plested

University of Oxford - Oxford Vaccine Group

Maheshi N. Ramasamy

University of Oxford - Oxford Vaccine Group

Hannah Robinson

University of Oxford - Oxford Vaccine Group

Helen Sanders

University of Oxford - The Jenner Institute

Emma Sheehan

University of Oxford - The Jenner Institute

Holly Smith

University of Oxford - The Jenner Institute

Matthew D. Snape

University of Oxford - Oxford Vaccine Group

Rinn Song

University of Oxford - Oxford Vaccine Group

Danielle Woods

University of Oxford - The Jenner Institute

Gavin R. Screaton

University of Oxford - Wellcome Centre for Human Genetics

Sarah C. Gilbert

University of Oxford - The Jenner Institute

Merryn Voysey

University of Oxford - Oxford Vaccine Group

Andrew Pollard

University of Oxford - Oxford Vaccine Group

Teresa Lambe

University of Oxford - The Jenner Institute

The Oxford COVID Vaccine Group

More...

Abstract

Background: COVID-19 vaccine supply shortages are causing concerns about compromised immunity in some countries as the interval between first and second dose extends. Conversely, countries with no supply constraints are considering administering a third dose. We assessed the persistence of immunogenicity after a single dose, the immunity after an extended interval between the first and second dose of ChAdOx1 nCoV-19(AZD1222), and the response to a third dose as a late booster.

Methods: Volunteers aged 18-55 years who were enrolled in a Phase 1/2 or Phase 2/3 clinical trial of ChAdOx1 nCoV-19 and had received either a single dose or two doses of 5×10 10 viral particles were invited back for vaccination. Reactogenicity and immunogenicity of a delayed second dose or a third dose are reported here.

Findings: Antibody titres after a single dose and measured on d362 remain higher than the titres measured on d0 (62.61 EU; 95% CI 47.43-82.64 vs 1 EU 95% CI 1-16). 30 participants received a late second dose of ChAdOx1 nCoV-19 (median 44 weeks after first dose), antibody titres were higher in those with a longer interval between first and second dose (median EU for 8-12, 15-25, and 44-46 weeks were 923 [IQR 525-1764], 1860 [IQR 917-4934] and 3738 [IQR 1824-6625] respectively). 90 participants received a third dose and antibody titres were significantly higher following a third dose (FRNT50 612 [IQR 351-920]) when compared with the response 28 days after a second dose (FRNT 50 319 [IQR 176-591]. T-cell responses were also boosted after a third dose. Reactogenicity after a late second dose or a third dose was lower than reactogenicity after a first dose.

Interpretation: A longer delay before the second dose of ChAdOx1 nCoV-19 leads to an increased antibody titre after the second dose. A third dose of ChAdOx1 nCoV-19 induces antibodies to a level that correlate with high efficacy after second dose and boosts T-cell responses.

Funding: UK Research and Innovation (MC_PC_19055), Engineering and Physical Sciences Research Council (EP/R013756/1), National Institute for Health Research (COV19 OxfordVacc-01), Coalition for Epidemic Preparedness Innovations (Outbreak Response To Novel Coronavirus (COVID-19)), National Institute for Health Research Oxford Biomedical Research Centre (BRC4 Vaccines Theme), Thames Valley and South Midland’s NIHR Clinical Research Network, and AstraZeneca. 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.

Declaration of Interest: Oxford University has entered into a partnership with AstraZeneca for further development of ChAdOx1 nCoV-19. AstraZeneca reviewed the data from the study and the final manuscript before submission, but the authors retained editorial control. SCG and AVSH are cofounders of and shareholders in Vaccitech (collaborators in the early development of this vaccine candidate) and named as inventors on a patent covering use of ChAdOx1-vectored vaccines (PCT/GB2012/000467) and a patent application covering this SARS-CoV-2 vaccine (SCG only). TL is named as an inventor on a patent covering use of ChAdOx1-vectored vaccines (PCT/GB2012/000467) and was a consultant to Vaccitech. PMF is a consultant to Vaccitech. AJP is Chair of the UK Department of Health and Social Care’s JCVI, but does not participate in policy advice on coronavirus vaccines, and is a member of the WHO Strategic Advisory Group of Experts (SAGE). AJP is a NIHR Senior Investigator.

Ethical Approval: In the UK, the COV001 and COV002 studies were approved by the South Central Berkshire Research Ethics Committee (COV001 reference 20/SC/0145, March 23, 2020; and COV002 reference 20/SC/0179; conditional approval April 8, full approval April 19, 2020).

Suggested Citation

Flaxman, Amy and Marchevsky, Natalie and Jenkin, Daniel and Aboagye, Jeremy and Aley, Parvinder K. and Angus, Brian John and Belij-Rammerstorfer, Sandra and Bibi, Sagida and Bittaye, Mustapha and Cappuccini, Federica and Cicconi, Paola and Clutterbuck, Elizabeth and Davies, Sophie and Dejnirattisai, Wanwisa and Dold, Christina and Ewer, Katie and Folegatti, Pedro M. and Fowler, Jamie and Hill, Adrian V. S. and Kerridge, Simon and Minassian, Angela M. and Mongkolspaya, Juthathip and Farooq Mujadidi, Yama and Plested, Emma and Ramasamy, Maheshi N. and Robinson, Hannah and Sanders, Helen and Sheehan, Emma and Smith, Holly and Snape, Matthew D. and Song, Rinn and Woods, Danielle and Screaton, Gavin R. and Gilbert, Sarah C. and Voysey, Merryn and Pollard, Andrew and Lambe, Teresa and Group, The Oxford COVID Vaccine, Tolerability and Immunogenicity After a Late Second Dose or a Third Dose of ChAdOx1 nCoV-19 (AZD1222). Available at SSRN: https://ssrn.com/abstract=3873839 or http://dx.doi.org/10.2139/ssrn.3873839

Amy Flaxman

University of Oxford - The Jenner Institute ( email )

Old Road Campus Research Building Roosevelt Drive
Oxford, Oxfordshire OX3 7DQ
United Kingdom

Natalie Marchevsky

University of Oxford - Oxford Vaccine Group

Mansfield Road
Oxford, OX1 4AU
United Kingdom

Daniel Jenkin

University of Oxford - The Jenner Institute

Mansfield Road
Oxford, OX1 4AU
United Kingdom

Jeremy Aboagye

University of Oxford - The Jenner Institute

Old Road Campus Research Building Roosevelt Drive
Oxford, Oxfordshire OX3 7DQ
United Kingdom

Parvinder K. Aley

University of Oxford - Oxford Vaccine Group

Mansfield Road
Oxford, OX1 4AU
United Kingdom

Brian John Angus

University of Oxford - The Jenner Institute

University of Oxford - Oxford Vaccine Group ( email )

Oxford
United Kingdom

Sandra Belij-Rammerstorfer

University of Oxford - The Jenner Institute ( email )

Mansfield Road
Oxford, Oxfordshire OX1 4AU
United Kingdom

Sagida Bibi

University of Oxford - Oxford Vaccine Group

Mansfield Road
Oxford, OX1 4AU
United Kingdom

Mustapha Bittaye

University of Oxford - The Jenner Institute ( email )

Mansfield Road
Oxford, Oxfordshire OX1 4AU
United Kingdom

Federica Cappuccini

University of Oxford - The Jenner Institute ( email )

Old Road Campus Research Building Roosevelt Drive
Oxford, Oxfordshire OX3 7DQ
United Kingdom

Paola Cicconi

University of Oxford - The Jenner Institute

Mansfield Road
Oxford, OX1 4AU
United Kingdom

University of Oxford - Oxford Vaccine Group ( email )

Oxford
United Kingdom

Elizabeth Clutterbuck

University of Oxford - Oxford Vaccine Group

Sophie Davies

University of Oxford - The Jenner Institute ( email )

Old Road Campus Research Building Roosevelt Drive
Oxford, Oxfordshire OX3 7DQ
United Kingdom

Wanwisa Dejnirattisai

University of Oxford - Wellcome Centre for Human Genetics ( email )

Oxford, OX3 7BN
United Kingdom

Christina Dold

University of Oxford - Oxford Vaccine Group ( email )

Oxford
United Kingdom

Katie Ewer

University of Oxford - The Jenner Institute ( email )

Old Road Campus Research Building Roosevelt Drive
Oxford, Oxfordshire OX3 7DQ
United Kingdom

Pedro M. Folegatti

University of Oxford - The Jenner Institute

Mansfield Road
Oxford, OX1 4AU
United Kingdom

Jamie Fowler

University of Oxford - The Jenner Institute ( email )

Old Road Campus Research Building Roosevelt Drive
Oxford, Oxfordshire OX3 7DQ
United Kingdom

Adrian V. S. Hill

University of Oxford - The Jenner Institute

Old Road Campus Research Building Roosevelt Drive
Oxford, Oxfordshire OX3 7DQ
United Kingdom

University of Oxford - Wellcome Trust Centre for Human Genetics ( email )

Old Road Campus
Roosevelt Drive
Oxford, OX3 7FZ
United Kingdom

University of Oxford - Centre for Clinical Vaccinology and Tropical Medicine ( email )

Oxford
United Kingdom

Simon Kerridge

University of Oxford - Oxford Vaccine Group

Mansfield Road
Oxford, OX1 4AU
United Kingdom

Angela M. Minassian

University of Oxford - The Jenner Institute

Mansfield Road
Oxford, OX1 4AU
United Kingdom

Juthathip Mongkolspaya

University of Oxford - Wellcome Centre for Human Genetics ( email )

Oxford, OX3 7BN
United Kingdom

Yama Farooq Mujadidi

University of Oxford - Oxford Vaccine Group

Emma Plested

University of Oxford - Oxford Vaccine Group

Mansfield Road
Oxford, OX1 4AU
United Kingdom

Maheshi N. Ramasamy

University of Oxford - Oxford Vaccine Group

Mansfield Road
Oxford, OX1 4AU
United Kingdom

Hannah Robinson

University of Oxford - Oxford Vaccine Group

Helen Sanders

University of Oxford - The Jenner Institute ( email )

Old Road Campus Research Building Roosevelt Drive
Oxford, Oxfordshire OX3 7DQ
United Kingdom

Emma Sheehan

University of Oxford - The Jenner Institute ( email )

Old Road Campus Research Building Roosevelt Drive
Oxford, Oxfordshire OX3 7DQ
United Kingdom

Holly Smith

University of Oxford - The Jenner Institute ( email )

Old Road Campus Research Building Roosevelt Drive
Oxford, Oxfordshire OX3 7DQ
United Kingdom

Matthew D. Snape

University of Oxford - Oxford Vaccine Group

Mansfield Road
Oxford, OX1 4AU
United Kingdom

Rinn Song

University of Oxford - Oxford Vaccine Group

Mansfield Road
Oxford, OX1 4AU
United Kingdom

Danielle Woods

University of Oxford - The Jenner Institute ( email )

Old Road Campus Research Building Roosevelt Drive
Oxford, Oxfordshire OX3 7DQ
United Kingdom

Gavin R. Screaton

University of Oxford - Wellcome Centre for Human Genetics ( email )

Oxford, OX3 7BN
United Kingdom

Sarah C. Gilbert

University of Oxford - The Jenner Institute ( email )

Old Road Campus Research Building Roosevelt Drive
Oxford, Oxfordshire OX3 7DQ
United Kingdom

Merryn Voysey

University of Oxford - Oxford Vaccine Group

Andrew Pollard

University of Oxford - Oxford Vaccine Group ( email )

United Kingdom

Teresa Lambe (Contact Author)

University of Oxford - The Jenner Institute ( email )

Old Road Campus Research Building Roosevelt Drive
Oxford, Oxfordshire OX3 7DQ
United Kingdom

No contact information is available for The Oxford COVID Vaccine Group

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