Valneva Austria, Vienna, Austria.
Valneva Austria, Vienna, Austria.
Lancet Infect Dis. 2024 Dec;24(12):1383-1392. doi: 10.1016/S1473-3099(24)00357-8. Epub 2024 Aug 12.
Chikungunya virus infection can lead to long-term debilitating symptoms. A precursor phase 3 clinical study showed high seroprotection (defined as a 50% plaque reduction of chikungunya virus-specific neutralising antibodies on a micro plaque reduction neutralisation test [μPRNT] titre of ≥150 in baseline seronegative participants) up to 6 months after a single vaccination of the chikungunya virus vaccine VLA1553 (Valneva Austria, Vienna, Austria) and a good safety profile. Here we report antibody persistence and safety up to 2 years.
In this single-arm, multicentre, phase 3b study, we recruited participants from the precursor phase 3 trial from professional vaccine trial sites in the USA. Participants (aged ≥18 years) were eligible if they had completed the previous study and received VLA1553. Chikungunya virus-specific neutralising antibodies were evaluated at 28 days, 6 months, and 1 year and 2 years after vaccination. The primary outcome was the proportion of seroprotected participants (ie, μPRNT titre of ≥150) at 1 and 2 years, assessed in all eligible participants who had at least one post-vaccination immunogenicity sample available, overall and by age group at the time of vaccination (18-64 years and ≥65 years). Adverse events of special interest at the time of transition from the previous study to the current study (ie, at 6 months) and serious adverse events during the current study were recorded (ie, between 6 months and 2 years). All analyses were descriptive. This study is registered with ClinicalTrials.gov, NCT04838444, and immunogenicity follow-up is ongoing.
In the precursor study, participants were screened between Sept 17, 2020, and April 10, 2021; data cutoff for this analysis was March 31, 2023. Of 2724 participants in the precursor study who received one dose of VLA1553, 363 participants were analysed in this study (310 [85%] aged 18-64 years and 53 [15%] aged ≥65 years at enrolment in the precursor study; mean age 47·7 years [SD 14·2], 207 [57%] of 363 participants were female, 156 [43%] were male, 280 [77%] were White, and 314 [87%] were not Hispanic or Latino). Strong seroprotection was observed at 1 year (98·9% [356 of 360 assessable participants; 97·2-99·7]) and 2 years (96·8% [306 of 316; 94·3-98·5]) after vaccination, and was very similar between those aged 18-64 years (at 1 year: 98·7% [303 of 307; 96·7-99·6]; at 2 years: 96·6% [256 of 265; 93·7-98·4]) and those aged 65 years and older (at 1 year: 100% [53 of 53; 93·3-100]; at 2 years: 98·0% [50 of 51; 89·6-100]) at each timepoint. No adverse events of special interest were ongoing at the time of transition. Ten serious adverse events occurred in nine (2%) participants between the 6-month and 2-year timepoints, including one death (due to drug overdose) that was determined to not be related to VLA1553.
After a single VLA1553 vaccination, chikungunya virus-neutralising antibodies above the threshold considered to be protective persisted up to 2 years and there were no long-term serious adverse events related to vaccination. VLA1553 is an efficient and safe intervention that offers high seroprotection against chikungunya virus infection, a virus likely to spread globally with an urgent demand for long-lasting prophylaxis.
Valneva Austria, Coalition for Epidemic Preparedness Innovation, and EU Horizon 2020.
基孔肯雅病毒感染可导致长期衰弱的症状。一项前期 3 期临床研究表明，在基线血清阴性的参与者中，微噬斑减少中和试验（μPRNT）滴度≥150 的 50%病毒中和抗体滴度保护率（定义为）高达 6 个月，可达到高达 150 的 50%病毒中和抗体滴度保护率（定义为），单次接种基孔肯雅病毒疫苗 VLA1553（瓦莱瓦奥地利，维也纳，奥地利）后具有良好的安全性。在此，我们报告了抗体持久性和安全性长达 2 年的情况。
在这项单臂、多中心、3b 期研究中，我们从美国的前期 3 期试验的专业疫苗试验点招募了参与者。符合条件的参与者（年龄≥18 岁）在前一项研究中完成并接受了 VLA1553 治疗。在接种后 28 天、6 个月、1 年和 2 年评估基孔肯雅病毒特异性中和抗体。主要终点是在 1 年和 2 年时的血清保护率（即 μPRNT 滴度≥150），在至少有一次接种后免疫原性样本的所有合格参与者中评估，总体和按接种时的年龄组评估（18-64 岁和≥65 岁）。在从前期研究过渡到当前研究时（即 6 个月时）记录特殊关注的不良事件和当前研究期间的严重不良事件（即 6 个月至 2 年）。所有分析均为描述性。本研究在 ClinicalTrials.gov 注册，NCT04838444，免疫接种随访正在进行中。
在前期研究中，参与者于 2020 年 9 月 17 日至 2021 年 4 月 10 日接受筛选；本分析的数据截止日期为 2023 年 3 月 31 日。在前期研究中接受了一剂 VLA1553 的 2724 名参与者中，有 363 名参与者在此研究中进行了分析（310 名[85%]年龄为 18-64 岁，53 名[15%]年龄为≥65 岁；平均年龄 47.7 岁[14.2]岁，207 名[57%]为女性，156 名[43%]为男性，280 名[77%]为白人，314 名[87%]不是西班牙裔或拉丁裔）。在接种后 1 年（98.9%[356 名可评估参与者；97.2-99.7%]）和 2 年（96.8%[306 名；94.3-98.5%]）观察到强烈的血清保护作用，在 18-64 岁和 65 岁及以上的年龄组之间非常相似（1 年时：98.7%[303 名；96.7-99.6%]；2 年时：96.6%[256 名；93.7-98.4%]）。在每个时间点，年龄在 65 岁及以上的参与者（1 年时：100%[53 名；93.3-100%]；2 年时：98.0%[50 名；89.6-100%]）和年龄在 18-64 岁的参与者（1 年时：98.7%[307 名；96.7-99.6%]；2 年时：96.6%[265 名；93.7-98.4%]）之间的相似性非常高。在过渡时没有正在进行的特殊关注的不良事件。9 名（2%）参与者在 6 个月至 2 年时间点之间发生了 10 例严重不良事件，包括 1 例死亡（由于药物过量），该死亡被确定与 VLA1553 无关。
在单次接种 VLA1553 后，高于被认为具有保护作用的阈值的基孔肯雅病毒中和抗体持续存在长达 2 年，并且没有与疫苗接种相关的长期严重不良事件。VLA1553 是一种高效且安全的干预措施，可提供针对基孔肯雅病毒感染的高血清保护率，该病毒可能在全球传播，对长期预防存在迫切需求。
瓦莱瓦奥地利、流行病防范创新联盟和欧盟地平线 2020。
