Background

Coronavirus-like particles (CoVLP) that are produced in plants and display the prefusion spike glycoprotein of the original strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are combined with an adjuvant (Adjuvant System 03 [AS03]) to form the candidate vaccine.

Methods

In this phase 3, multinational, randomized, placebo-controlled trial conducted at 85 centers, we assigned adults (≥18 years of age) in a 1:1 ratio to receive two intramuscular injections of the CoVLP+AS03 vaccine or placebo 21 days apart. The primary objective of the trial was to determine the efficacy of the CoVLP+AS03 vaccine in preventing symptomatic coronavirus disease 2019 (Covid-19) beginning at least 7 days after the second injection, with the analysis performed after the detection of at least 160 cases.

Results

A total of 24,141 volunteers participated in the trial; the median age of the participants was 29 years. Covid-19 was confirmed by polymerase-chain-reaction assay in 165 participants in the intention-to-treat population; all viral samples that could be sequenced contained variants of the original strain. Vaccine efficacy was 69.5% (95% confidence interval [CI], 56.7 to 78.8) against any symptomatic Covid-19 caused by five variants that were identified by sequencing. In a post hoc analysis, vaccine efficacy was 78.8% (95% CI, 55.8 to 90.8) against moderate-to-severe disease and 74.0% (95% CI, 62.1 to 82.5) among the participants who were seronegative at baseline. No severe cases of Covid-19 occurred in the vaccine group, in which the median viral load for breakthrough cases was lower than that in the placebo group by a factor of more than 100. Solicited adverse events were mostly mild or moderate and transient and were more frequent in the vaccine group than in the placebo group; local adverse events occurred in 92.3% and 45.5% of participants, respectively, and systemic adverse events in 87.3% and 65.0%. The incidence of unsolicited adverse events was similar in the two groups up to 21 days after each dose (22.7% and 20.4%) and from day 43 through day 201 (4.2% and 4.0%).

Conclusions

The CoVLP+AS03 vaccine was effective in preventing Covid-19 caused by a spectrum of variants, with efficacy ranging from 69.5% against symptomatic infection to 78.8% against moderate-to-severe disease. (Funded by Medicago; ClinicalTrials.gov number, NCT04636697.)

中文翻译：

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基于植物的重组 Covid-19 佐剂疫苗的功效和安全性

背景

冠状病毒样颗粒 (CoVLP) 在植物中产生并显示严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 原始菌株的融合前刺突糖蛋白，与佐剂 (Adjuvant System 03 [AS03]) 结合形成候选疫苗。

方法

在这个在 85 个中心进行的多国、随机、安慰剂对照试验的第 3 阶段中，我们以 1:1 的比例分配成年人（≥18 岁）接受两次肌肉注射 CoVLP+AS03 疫苗或安慰剂，间隔 21 天. 该试验的主要目的是确定 CoVLP+AS03 疫苗在第二次注射后至少 7 天开始预防症状性冠状病毒病 2019 (Covid-19) 的功效，并在检测到至少 160 例病例后进行分析.

结果

共有24141名志愿者参加了试验；参与者的中位年龄为29岁。Covid-19 在意向治疗人群中的 165 名参与者中通过聚合酶链反应测定得到证实；所有可以测序的病毒样本都含有原始毒株的变体。针对由测序鉴定的五种变异引起的任何症状性 Covid-19，疫苗的有效性为 69.5%（95% 置信区间 [CI]，56.7 至 78.8）。在一项事后分析中，疫苗对中度至重度疾病的有效性为 78.8%（95% CI，55.8 至 90.8），在基线时血清阴性的参与者中为 74.0%（95% CI，62.1 至 82.5）。疫苗组没有出现严重的 Covid-19 病例，其中突破病例的中位病毒载量比安慰剂组低 100 多倍。引起的不良事件大多是轻度或中度和短暂的，并且在疫苗组中比在安慰剂组中更频繁；局部不良事件发生率分别为 92.3% 和 45.5%，全身性不良事件发生率分别为 87.3% 和 65.0%。两组在每次给药后长达 21 天（22.7% 和 20.4%）以及从第 43 天到第 201 天（4.2% 和 4.0%）的主动不良事件发生率相似。

结论

CoVLP+AS03 疫苗可有效预防由一系列变异引起的 Covid-19，其功效范围从针对症状感染的 69.5% 到针对中重度疾病的 78.8%。（由 Medicago 资助；ClinicalTrials.gov 编号为 NCT04636697。）