The vaccine developed by the University of Oxford and AstraZeneca has the potential to slow the transmission of the virus, according to a new paper:
Single Dose Administration, And The Influence Of The Timing Of The Booster Dose On Immunogenicity and Efficacy Of ChAdOx1 nCoV-19 (AZD1222) Vaccine

37 Pages Posted: 1 Feb 2021
Merryn Voysey

University of Oxford – Oxford Vaccine Group
Sue Ann Costa Clemens

University of Siena – Institute of Global Health
Shabir A. Madhi

University of the Witwatersrand – South African Medical Research Council Vaccines and Infectious Diseases Analytical Research Unit
Lily Yin Weckx

Federal University of Sao Paulo
Pedro M. Folegatti

University of Oxford – Jenner Institute
Parvinder K. Aley

University of Oxford – Oxford Vaccine Group
Brian John Angus

University of Oxford – Jenner Institute
Vicky Baillie

University of the Witwatersrand
Shaun L. Barnabas

Soweto Clinical Trials Centre
Qasim E. Bhorat

Soweto Clinical Trials Centre
Sagida Bibi

University of Oxford – Oxford Vaccine Group
Carmen Briner

Setshaba Research Centre
Paola Cicconi

University of Oxford – Jenner Institute
Elizabeth Clutterbuck

University of Oxford – Oxford Vaccine Group
Andrea M. Collins

Liverpool School of Tropical Medicine – Department of Clinical Sciences
Clare Cutland

University of the Witwatersrand – South African Medical Research Council Vaccines and Infectious Diseases Analytical Research Unit
Thomas Darton

University of Sheffield – Department of Infection, Immunity and Cardiovascular Disease
Keertan Dheda

University of Cape Town – Centre for Lung Infection and Immunology
Alexander D. Douglas

University of Oxford – Jenner Institute
Christopher J. A. Duncan

Newcastle upon Tyne Hospitals NHS Foundation Trust – Department of Infection and Tropical Medicine
Katherine R. W. Emary

University of Oxford – Oxford Vaccine Group
Katie Ewer

University of Oxford – Jenner Institute
Amy Flaxman

University of Oxford – Jenner Institute
Lee Fairlie

Wits Reproductive Health & HIV Institute (WRHI)
Saul N. Faust

University of Southampton – NIHR Southampton Clinical Research Facility and Biomedical Research Centre
Shuo Feng

University of Oxford – Oxford Vaccine Group
Daniela M. Ferreira

Liverpool School of Tropical Medicine – Department of Clinical Sciences
Adam Finn

University Hospitals Bristol and Weston NHS Foundation Trust
Eva Galiza

University of London – St George’s Vaccine Institute
Anna L. Goodman

University College London – Department of Infection
Catherine M. Green

University of Oxford – Clinical BioManufacturing Facility
Christopher A. Green

University Hospitals Birmingham NHS Foundation Trust
Melanie Greenland

University of Oxford – Oxford Vaccine Group
Catherine Hill

University of the Witwatersrand – South African Medical Research Council
Helen C. Hill

Liverpool School of Tropical Medicine – Department of Clinical Sciences
Ian Hirsch

AstraZeneca Pharmaceuticals
Alane Izu

University of the Witwatersrand – South African Medical Research Council
Daniel Jenkin

University of Oxford – Jenner Institute
Simon Kerridge

University of Oxford – Oxford Vaccine Group
Anthonet Koen

University of the Witwatersrand – South African Medical Research Council
Gaurav Kwatra

University of the Witwatersrand – South African Medical Research Council
Rajeka Lazarus

North Bristol NHS Trust – Severn Pathology
Vincenzo Libri

NIHR UCLH Clinical Research Facility
Patrick J. Lillie

Hull University Teaching Hospitals NHS Trust
Natalie G. Marchevsky

University of Oxford
Richard P. Marshall

AstraZeneca Pharmaceuticals
Ana Verena Almeida Mendes

Braziland Hospital São Rafael – Escola Bahiana de Medicina e Saúde Pública
Eveline P. Milan

Universidade Federal do Rio Grande do Norte (UFRN)
Angela M. Minassian

University of Oxford – Jenner Institute
Alastair C. McGregor

London Northwest University Healthcare
Yama Farooq Mujadidi

University of Oxford – Oxford Vaccine Group
Anusha Nana

University of the Witwatersrand – Perinatal HIV Research Unit
Sherman D. Payadachee

Setshaba Research Centre
Daniel J. Phillips

University of Oxford – Oxford Vaccine Group
Ana Pittella

Hospital Quinta D’OR
Emma Plested

University of Oxford – Oxford Vaccine Group
Katrina M. Pollock

NIHR Imperial Clinical Research Facility
Maheshi N. Ramasamy

University of Oxford – Oxford Vaccine Group
Hannah Robinson

University of Oxford – Oxford Vaccine Group
Alexandre V. Schwarzbold

Federal University of Santa Maria (UFSM) – Clinical Research Unit
Andrew Smith

University of Glasgow – College of Medical, Veterinary & Life Sciences
Rinn Song

University of Oxford – Oxford Vaccine Group
Matthew D. Snape

University of Oxford – Oxford Vaccine Group
Eduardo Sprinz

Universidade Federal do Rio Grande do Sul
Rebecca K. Sutherland

Western General Hospital – Clinical Infection Research Group
Emma C. Thomson

Queen Elizabeth University Hospital
Mili Torok

University of Cambridge – Department of Medicine
Mark Toshner

Royal Papworth Hospital
David P. J. Turner

University of Nottingham
Johan Vekemans

AstraZeneca Pharmaceuticals
Tonya L. Villafana

AstraZeneca Pharmaceuticals
Thomas White

AstraZeneca Pharmaceuticals
Christopher J. Williams

Anuerin Bevan University Health Board
Adrian V. S. Hill

University of Oxford – Wellcome Trust Centre for Human Genetics; University of Oxford – Jenner Institute
Teresa Lambe

University of Oxford – Jenner Institute
Sarah C. Gilbert

University of Oxford – Jenner Institute
Andrew Pollard

University of Oxford – Oxford Vaccine Group
Oxford COVID Vaccine Trial Group
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Abstract

Background: The ChAdOx1 nCoV-19 (AZD1222) vaccine has been approved for emergency use by the UK regulatory authority, MHRA, with a regimen of two standard doses given with an interval of between 4 and 12 weeks. The planned rollout in the UK will involve vaccinating people in high risk categories with their first dose immediately, and delivering the second dose 12 weeks later.Here we provide both a further prespecified pooled analysis of trials of ChAdOx1 nCoV-19 and exploratory analyses of the impact on immunogenicity and efficacy of extending the interval between priming and booster doses. In addition, we show the immunogenicity and protection afforded by the first dose, before a booster dose has been offered.

Methods: We present data from phase III efficacy trials of ChAdOx1 nCoV-19 in the United Kingdom and Brazil, and phase I/II clinical trials in the UK and South Africa, against symptomatic disease caused by SARS-CoV-2. The data cut-off date for these analyses was 7th December 2020. The accumulated cases of COVID-19 disease at this cut-off date exceeds the number required for a pre-specified final analysis, which is also presented. As previously described, individuals over 18 years of age were randomised 1:1 to receive two standard doses (SD) of ChAdOx1 nCoV-19 (5×1010 viral particles) or a control vaccine/saline placebo. In the UK trial efficacy cohort a subset of participants received a lower dose (LD, 2.2×1010 viral particles) of the ChAdOx1 nCoV-19 for the first dose. All cases with a nucleic acid amplification test (NAAT) were adjudicated for inclusion in the analysis, by a blinded independent endpoint review committee. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov; NCT04324606, NCT04400838, and NCT04444674.

Findings: 17,177 baseline seronegative trial participants were eligible for inclusion in the efficacy analysis, 8948 in the UK, 6753 in Brazil and 1476 in South Africa, with 619 documented NAAT +ve infections of which 332 met the primary endpoint of symptomatic infection >14 days post dose 2.The primary analysis of overall vaccine efficacy >14 days after the second dose including LD/SD and SD/SD groups, based on the prespecified criteria was 66.7% (57.4%, 74.0%). There were no hospitalisations in the ChAdOx1 nCoV-19 group after the initial 21 day exclusion period, and 15 in the control group.Vaccine efficacy after a single standard dose of vaccine from day 22 to day 90 post vaccination was 76% (59%, 86%), and modelled analysis indicated that protection did not wane during this initial 3 month period. Similarly, antibody levels were maintained during this period with minimal waning by day 90 day (GMR 0.66, 95% CI 0.59, 0.74).In the SD/SD group, after the second dose, efficacy was higher with a longer prime-boost interval: VE 82.4% 95%CI 62.7%, 91.7% at 12+ weeks, compared with VE 54.9%, 95%CI 32.7%, 69.7% at <6 weeks. These observations are supported by immunogenicity data which showed binding antibody responses more than 2-fold higher after an interval of 12 or more weeks compared with and interval of less than 6 weeks GMR 2.19 (2.12, 2.26) in those who were 18-55 years of age.

Interpretation: ChAdOx1 nCoV-19 vaccination programmes aimed at vaccinating a large proportion of the population with a single dose, with a second dose given after a 3 month period is an effective strategy for reducing disease, and may be the optimal for rollout of a pandemic vaccine when supplies are limited in the short term.

Trial Registration: Studies are registered at ISRCTN89951424 and ClinicalTrials.gov; NCT04324606, NCT04400838, and NCT04444674.

Funding: UKRI, NIHR, CEPI, the Bill & Melinda Gates Foundation, the Lemann Foundation, Rede D’OR, the Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and Astra Zeneca.

Conflict of Interest: Oxford University has entered into a partnership with Astra Zeneca for further development of ChAdOx1 nCoV-19. SCG is co-founder of Vaccitech (collaborators in the early development of this vaccine candidate) and named as an inventor on a patent covering use of ChAdOx1-vectored vaccines and a patent application covering this SARS-CoV-2 vaccine. TL is named as aninventor on a patent application covering this SARS-CoV-2 vaccine and was a consultant to Vaccitech for an unrelated project. PMF is a consultant to Vaccitech. AJP is Chair of UK Dept.Health and Social Care’s (DHSC) Joint Committee on Vaccination & Immunisation (JCVI), but does not participate in discussions on COVID-19 vaccines, and is a member of the WHO’sSAGE. AJP and SNF are NIHR Senior Investigator. The views expressed in this article do not necessarily represent the views of DHSC, JCVI, NIHR or WHO. AVSH reports personal feesfrom Vaccitech, outside the submitted work and has a patent on ChAdOx1 licensed to Vaccitech, and may benefit from royalty income to the University of Oxford from sales of this vaccine by AstraZeneca and sublicensees. MS reports grants from NIHR, non-financial support fromAstraZeneca, during the conduct of the study; grants from Janssen, grants fromGlaxoSmithKline, grants from Medimmune, grants from Novavax, grants and non-financialsupport from Pfizer, grants from MCM, outside the submitted work. CG reports personal fees from the Duke Human Vaccine Institute, outside of the submitted work. SNF reports grants from Janssen and Valneva, outside the submitted work. ADD reports grants and personal fees from AstraZeneca, outside of the submitted work. In addition, ADD has a patent manufacturingprocess for ChAdOx vectors with royalties paid to AstraZeneca, and a patent ChAdOx2 vector with royalties paid to AstraZeneca. The other authors declare no competing interests.