Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials

Abstract

Background The ChAdOx1 nCoV-19 (AZD1222) vaccine has been approved for emergency use by the UK regulatory authority, Medicines and Healthcare products Regulatory Agency, with a regimen of two standard doses given with an interval of 4–12 weeks. The planned roll-out 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 three single-blind randomised controlled trials—one phase 1/2 study in the UK (COV001), one phase 2/3 study in the UK (COV002), and a phase 3 study in Brazil (COV003)—and one double-blind phase 1/2 study in South Africa (COV005). As previously described, individuals 18 years and older were randomly assigned 1:1 to receive two standard doses of ChAdOx1 nCoV-19 (5 × 10 10 viral particles) or a control vaccine or saline placebo. In the UK trial, a subset of participants received a lower dose (2·2 × 10 10 viral particles) of the ChAdOx1 nCoV-19 for the first dose. The primary outcome was virologically confirmed symptomatic COVID-19 disease, defined as a nucleic acid amplification test (NAAT)-positive swab combined with at least one qualifying symptom (fever ≥37·8°C, cough, shortness of breath, or anosmia or ageusia) more than 14 days after the second dose. Secondary efficacy analyses included cases occuring at least 22 days after the first dose. Antibody responses measured by immunoassay and by pseudovirus neutralisation were exploratory outcomes. All cases of COVID-19 with a NAAT-positive swab were adjudicated for inclusion in the analysis by a masked independent endpoint review committee. The primary analysis included all participants who were SARS-CoV-2 N protein seronegative at baseline, had had at least 14 days of follow-up after the second dose, and had no evidence of previous SARS-CoV-2 infection from NAAT swabs. Safety was assessed in all participants who received at least one dose. The four trials are registered at ISRCTN89951424 (COV003) and ClinicalTrials.gov , NCT04324606 (COV001), NCT04400838 (COV002), and NCT04444674 (COV005). Findings Between April 23 and Dec 6, 2020, 24 422 participants were recruited and vaccinated across the four studies, of whom 17 178 were included in the primary analysis (8597 receiving ChAdOx1 nCoV-19 and 8581 receiving control vaccine). The data cutoff for these analyses was Dec 7, 2020. 332 NAAT-positive infections met the primary endpoint of symptomatic infection more t...

An observational cohort study on the incidence of SARS-CoV-2 infection and B.1.1.7 variant infection in healthcare workers by antibody and vaccination status

“…Single dose vaccine efficacy >22 days post-first dose has been reported as 69-76%. 14,15 No real-world data on vaccine effectiveness against PCR-positive infections has been published, but preliminary analyses show a reduction in hospital admissions in Scotland. 16 A novel SARS-CoV-2 variant, B.1.1.7, identified in September-2020 in the UK, has spread rapidly.…”

Modelled Optimization of SARS-Cov-2 Vaccine Distribution: an Evaluation of Second Dose Deferral Spacing of 6, 12, and 24 weeks

“…A common concern about implementing the deferred second dose strategy is that the one dose efficacy duration is unknown for now. AstraZeneca’s one dose trial data showed sustained one dose immunity for at least 12 weeks (13), but given that it did not use the novel mRNA vaccine technology, the concern around one dose duration was still valid. However, with multiple ongoing studies evaluating one dose efficacy duration of the mRNA vaccines (such as in Quebec and the UK), this risk has greatly been diminished.…”

Seven days in medicine: 17-23 February 2021

“…A three month interval between doses of the Oxford-AstraZeneca vaccine results in higher vaccine efficacy (81%) than only a six week interval (55%), and the first dose offers 76% protection from 22 days onwards, showed the results of post-hoc exploratory analyses from a phase III randomised controlled trial published in the Lancet 1. The study, which was published as a preprint at the start of February,2 also confirmed vaccine efficacy against symptomatic disease after two doses, with no hospital admissions or deaths among the people vaccinated (8597 participants), compared with 15 instances in the control group (8581).…”