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Immunogenicity and safety of an inactivated whole-virus COVID-19 vaccine (VLA2001) compared with the adenoviral vector vaccine ChAdOx1-S in adults in the UK (COV-COMPARE): interim analysis of a randomised, controlled, phase 3, immunobridging trial
The Lancet Infectious Diseases ( IF 56.3 ) Pub Date : 2022-09-05 , DOI: 10.1016/s1473-3099(22)00502-3
Rajeka Lazarus 1 , Benedicte Querton 2 , Irena Corbic Ramljak 2 , Shailesh Dewasthaly 2 , Juan Carlos Jaramillo 2 , Katrin Dubischar 2 , Michael Krammer 2 , Petronela Weisova 2 , Romana Hochreiter 2 , Susanne Eder-Lingelbach 2 , Christian Taucher 2 , Adam Finn 3 ,
Affiliation  

Background

The Valneva COVID-19 vaccine (VLA2001; Valneva Austria, Vienna, Austria) is an inactivated whole-virus, adjuvanted SARS-CoV-2 vaccine. We aimed to assess the safety and immunogenicity of primary vaccination with VLA2001 versus the ChAdOx1-S (Oxford-AstraZeneca) adenoviral-vectored vaccine.

Methods

In this immunobridging phase 3 trial (COV-COMPARE), participants aged 18 years and older who were medically stable (as determined by an investigator) were enrolled at 26 sites in the UK. In the double-blind, randomised, controlled arm of the trial, participants aged 30 years and older were randomly assigned (2:1) to receive two doses of VLA2001 (0·5 mL; with 33 antigen units [AU] per dose) or ChAdOx1-S (0·5 mL; with 2·5 × 108 infectious units per dose) on days 1 and 29. In another arm, participants aged 18–29 years received two doses of VLA2001 (same dose) open label on days 1 and 29. The primary immunogenicity outcome was the immune response of a two-dose schedule of VLA2001 on day 43, in adults aged 30 years and older, versus two doses of ChAdOx1-S via superiority of geometric mean titres (GMTs) of neutralising antibodies (GMT ratio of >1 at a two-sided significance level of 5%) and non-inferiority of the seroconversion rate (non-inferiority margin of –10% for the lower limit of the 95% CI for the difference between groups). The primary safety outcome was the frequency and severity of any adverse events in all participants up to day 43. Safety was assessed in all participants who received at least one dose of vaccine. GMTs were assessed in a subset of participants aged 30 years and older who were seronegative at baseline, had at least one evaluable antibody titre measurement after vaccination, and had no confirmed COVID-19 during the study (immunogenicity population); and seroconversion was assessed in the per-protocol population, which comprised the immunogenicity population but excluding any participants with major protocol violations. For each timepoint, only participants with available data were included in the analysis. This study is registered with ClinicalTrials.gov, NCT04864561, and is ongoing.

Findings

Between April 28 and June 3, 2021, 4181 individuals were screened and 4017 enrolled, of whom 2975 (74%) were aged 30 years or older and randomly assigned to receive VLA2001 (n=1978) or ChAdOx1-S (n=997), and 1042 (26%) were aged 18–29 years (all received open-label VLA2001). 4012 participants received at least one dose of vaccine (1040 in the open-label VLA2001 group, 1977 in the randomised VLA2001 group, and 995 in the ChAdOx1-S group). The immunogenicity population comprised 492 participants in the randomised VLA2001 group and 498 in the ChAdOx1-S group; three participants in the VLA2001 group were excluded from the per-protocol population. VLA2001 induced higher neutralising GMTs than did ChAdOx1-S (803·5 [95% CI 748·5–862·6] vs 576·6 [543·6–611·7]; GMT ratio 1·39 [95% CI 1·25–1·56]; p<0·0001), and non-inferior seroconversion rates (444 [97·4%] of 456 participants vs 444 [98·9%] of 449; difference –1·5% [95% CI –3·3 to 0·2]. Any adverse event was reported in 963 (92·6%) participants in the open-label VLA2001 group, 1755 (88·8%) in the randomised VLA2001 group, and 976 (98·1%) in the ChAdOx1-S group. Most adverse events reported were mild or moderate in severity.

Interpretation

VLA2001 has a favourable tolerability profile and met superiority criteria for neutralising antibodies and non-inferiority criterion for seroconversion rates compared with ChAdOx1-S. The data presented here formed the basis of successful marketing approval for use of VLA2001 in primary vaccination in the EU, the UK, Bahrain, and United Arab Emirates.

Funding

UK Department of Health and Social Care and Valneva Austria.



中文翻译:

与英国成人腺病毒载体疫苗 ChAdOx1-S 相比,灭活全病毒 COVID-19 疫苗 (VLA2001) 的免疫原性和安全性 (COV-COMPARE):随机、对照、3 期免疫桥接试验的中期分析

背景

Valneva COVID-19 疫苗(VLA2001;Valneva Austria,奥地利维也纳)是一种灭活的全病毒佐剂 SARS-CoV-2 疫苗。我们的目的是评估 VLA2001 与 ChAdOx1-S(牛津-阿斯利康)腺病毒载体疫苗初次接种疫苗的安全性和免疫原性。

方法

在这项免疫桥接 3 期试验 (COV-COMPARE) 中,年龄在 18 岁及以上且身体状况稳定(由研究者确定)的参与者在英国的 26 个地点入选。在该试验的双盲、随机、对照组中,年龄在 30 岁及以上的参与者被随机分配 (2:1) 接受两剂 VLA2001(0·5 mL;每剂含 33 个抗原单位 [AU])或 ChAdOx1-S(0·5 mL;用 2·5 × 10 8每剂感染单位)在第 1 天和第 29 天。在另一组中,年龄在 18-29 岁的参与者在第 1 天和第 29 天接受了两剂 VLA2001(相同剂量)开放标签。主要免疫原性结果是双- VLA2001 在第 43 天的给药方案,在 30 岁及以上的成年人中,与两剂 ChAdOx1-S 相比,通过中和抗体的几何平均滴度 (GMT) 的优势(GMT 比率 > 1,双侧显着性水平为 5) %)和血清转化率的非劣效性(组间差异的 95% CI 下限的非劣效性界值为 –10%)。主要安全性结果是所有参与者在第 43 天之前发生任何不良事件的频率和严重程度。对接受至少一剂疫苗的所有参与者的安全性进行了评估。在基线时血清阴性、接种疫苗后至少进行过一次可评估的抗体滴度测量且在研究期间未确诊 COVID-19(免疫原性人群)的部分 30 岁及以上的参与者中评估了 GMT;并且在符合方案人群中评估了血清转化,该人群包括免疫原性人群,但不包括任何严重违反方案的参与者。对于每个时间点,分析中仅包括具有可用数据的参与者。这项研究已在 ClinicalTrials.gov 注册,NCT04864561,并且正在进行中。并且在符合方案人群中评估了血清转化,该人群包括免疫原性人群,但不包括任何严重违反方案的参与者。对于每个时间点,分析中仅包括具有可用数据的参与者。这项研究已在 ClinicalTrials.gov 注册,NCT04864561,并且正在进行中。并且在符合方案人群中评估了血清转化,该人群包括免疫原性人群,但不包括任何严重违反方案的参与者。对于每个时间点,分析中仅包括具有可用数据的参与者。这项研究已在 ClinicalTrials.gov 注册,NCT04864561,并且正在进行中。

发现

2021 年 4 月 28 日至 6 月 3 日期间,对 4181 人进行了筛选并招募了 4017 人,其中 2975 人 (74%) 年龄在 30 岁或以上,并随机分配接受 VLA2001 (n=1978) 或 ChAdOx1-S (n=997) , 1042 人 (26%) 年龄在 18-29 岁之间(所有人都接受了开放标签 VLA2001)。4012 名参与者至少接种了一剂疫苗(开放标签 VLA2001 组 1040 人,随机 VLA2001 组 1977 人,ChAdOx1-S 组 995 人)。免疫原性人群包括随机 VLA2001 组的 492 名参与者和 ChAdOx1-S 组的 498 名参与者;VLA2001 组的三名参与者被排除在符合方案人群之外。VLA2001 诱导比 ChAdOx1-S 更高的中和 GMT(803·5 [95% CI 748·5–862·6] vs576·6 [543·6–611·7];GMT 比率 1·39 [95% CI 1·25–1·56];p<0·0001)和非劣效血清转化率(456 名参与者中的 444 [97·4%]449 名参与者中的 444 [98·9%];差异 –1·5% [95% CI –3·3 至0·2]. 开放标签 VLA2001 组 963 名 (92·6%) 参与者、随机 VLA2001 组 1755 名 (88·8%) 参与者和随机 VLA2001 组 976 名 (98·1%) 参与者报告了任何不良事件ChAdOx1-S 组。报告的大多数不良事件的严重程度为轻度或中度。

解释

与 ChAdOx1-S 相比,VLA2001 具有良好的耐受性,并且满足中和抗体的优势标准和血清转化率的非劣效性标准。此处提供的数据构成了 VLA2001 在欧盟、英国、巴林和阿拉伯联合酋长国的初级疫苗接种中成功上市许可的基础。

资金

英国卫生和社会保健部和奥地利 Valneva。

更新日期:2022-09-05
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