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...
Ever-increasing global trade is one of the most important introduction pathways for plant pests. A diverse range of risk-reducing measures can be applied depending on the pest, the commodity and the import requirements. We used a review of over 1,800 risk reduction measures to extend a risk framework and menu of measures, previously developed for horticulture, to be applied to any commodity. We also reviewed how the efficacy of risk reduction measures is demonstrated, and assessed the maturity of the supporting science. We identified 39 unique risk reduction measures that were classified according to how they reduce risk. These were grouped under ten measure categories and four risk reduction objectives (minimising exposure to pest, minimising vulnerability of the commodity, reducing infestation rate and reducing establishment risk). These could then be applied against one or more consignment stages (production, post-production and post-border). Measures covered both commercial activities that reduce risk and may contribute to pest risk assessment, and regulated measures mandated to address unrestricted risk. Almost 90% of citations included measures that minimised exposure to pests or reduced infestation. Some measures were rarely reported, and some commodity classes had few measures associated with them, suggesting that available measures are being underutilised. Clear guidance was apparent for demonstrating efficacy of some measures (e.g., kill treatments), but lacking for many others. Compiling a ‘menu of risk reduction measures’ according to how they reduce risk, accompanied by clear guidelines for demonstrating efficacy, provides a robust basis for agreement between jurisdictions, and the further development, refinement and communication of efforts to both assess and manage the risk of global, trade-related pest movement. Agreement on how efficacy can be demonstrated for less utilised measures identified in this study will contribute to the further development of risk-based trade.
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