One dose of the Oxford/AstraZeneca vaccine provides sustained protection against COVID-19 for at least three months and cuts transmission of the virus by two-thirds. Researchers at the University of Oxford have published an analysis of further data from the ongoing trials of the vaccine. In this, they reveal that the vaccine efficacy is higher at longer prime-boost intervals, and that a single dose of the vaccine is 76% effective from 22- to up to 90-days post vaccination.
In this preprint, which is currently under review, they report on an analysis of additional data to include information from the trial up to the 7th December 2020, which includes a further 201 cases of primary symptomatic COVID-19 (332 cases from 131 reported in previously), They report that the effect of dosing interval on efficacy is pronounced, with vaccine efficacy rising from 54.9% with an interval of less than six weeks to 82.4% when spaced 12 or more weeks apart.
They also detail that a single standard dose of the vaccine is 76% effective at protecting from primary symptomatic COVID-19 for the first 90 days post vaccination, once the immune system has built this protection 22 days after the vaccination, with the protection showing little evidence of waning in this period.
Professor Andrew Pollard, chief investigator of the Oxford Vaccine Trial, and co-author, said: “These new data provide an important verification of the interim data that was used by more than 25 regulators including the UK's Medicines and Healthcare Products Regulatory Agency (MHRA) and the European Medicines Agency (EMA) to grant the vaccine emergency use authorisation.
“It also supports the policy recommendation made by the Joint Committee on Vaccination and Immunisation (JCVI) for a 12-week prime-boost interval, as they look for the optimal approach to roll out, and reassures us that people are protected from 22 days after a single dose of the vaccine.”
The exploratory analyses presented in this preprint suggest that it is the dosing interval and not the dosing level which has a great impact on the efficacy of the vaccine. This is in line with previous research supporting greater efficacy with longer prime-boost intervals done with other vaccines such as influenza, Ebola and malaria.
The authors also report further on the potential for the vaccine to reduce transmission of the virus, based on swabs obtained from volunteers in the UK arms of the trial with a 67% reduction after the first dose of the vaccine.
They also hope to report data regarding the new variants in the coming days, and expect the findings to be broadly similar to those already reported by fellow vaccine developers.
Study details
Single Dose Administration, And The Influence Of The Timing Of The Booster Dose On Immunogenicity and Efficacy Of ChAdOx1 nCoV-19 (AZD1222) Vaccine
Merryn Voysey, Sue Ann Costa Clemens
Published in The Lancet on 1 February 2021
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.
[link url="https://www.ox.ac.uk/news/2021-02-02-oxford-coronavirus-vaccine-shows-sustained-protection-76-during-3-month-interval"]University of Oxford material[/link]
[link url="https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3777268"]The Lancet study pre-print[/link]