加拿大北部巴伐利亚Lisa Bedell小组揭示了美国青少年和成人基孔肯雅病毒样颗粒疫苗的安全性和免疫原性。这一研究成果于2025年3月27日发表在国际顶尖学术期刊《柳叶刀》上。

背景:基孔肯雅病是一个日益严重的全球公共卫生问题。Vimkunya（以前是基孔肯雅病毒样颗粒疫苗，以前是PXVX0317）是一种单剂量预充注射器，用于肌肉注射。在这里，课题组报告了Vimkunya与安慰剂在12-64岁健康青少年和成年人中的安全性、耐受性和免疫原性数据，并评估了批次间一致性。

方法:这项关键的3期、随机、双盲、安慰剂对照、平行组试验在美国的47个临床试验点进行。符合条件的参与者是12-64岁的健康青少年和成年人。在每个研究地点，参与者被分为三个年龄层（12-17岁，18-45岁和46-64岁），并随机分配（2:2:2:1）在研究第一天接受三个连续生产批次的Vimkunya或安慰剂（相同的辅料成分，不含基孔肯雅病毒样颗粒或氢氧化铝成分）中的一个。参与者、临床现场人员和资助者都不认识参与者'；个体治疗分配，直到所有参与者完成他们的参与试验，数据库被清理和锁定。参与者参加了一次筛选访问，随后是第一天的访问，包括随机分配，血液样本收集，以及通过三角肌肌内注射单剂量Vimkunya或安慰剂。主要终点为：第22天基孔肯雅病毒血清中和抗体血清反应率（疫苗减去安慰剂）的差异；基孔肯雅病毒血清中和抗体几何平均滴度（GMT）在疫苗和安慰剂的第22天；以及18-45岁成人中所有三对疫苗批次（A:B、B:C和A:C）在第22天基孔肯雅病毒血清中和GMT比率。

发现:在2021年9月29日至2022年9月23日期间，筛选了4215名参与者，其中3258名符合条件并入组（1667名[51.2%]女性和1591名[48.8%]男性），3254名（99.9%）接受了Vimkunya （n=2790）或安慰剂（n=464）。免疫原性可评估人群包括2983名参与者，其中2559人接受Vimkunya治疗，424人接受安慰剂治疗。在免疫原性可评估人群中，Vimkunya组2559名参与者中有2503名（97.8%）出现血清反应，而安慰剂组424名参与者中有5名（1.2%）出现血清反应。血清反应率差异为96.6% (95% CI为95.0 ~ 97.5；术;0·0001)。在免疫原性可评估的人群中，基孔肯雅病毒血清中和抗体GMT在第22天疫苗组为1618，安慰剂组为7.9 （p< 0.0001）。第22天，各组（A:B、B:C和A:C）的血清中和GMT比值分别为0.98 （95% CI 0.85 - 1.14）、0.97（0.84 - 1.12）和0.95（0.82 - 1.10）。Vimkunya具有良好的安全概况；大多数不良事件是自限性的，严重程度为1或2级。最常见的不良事件是注射部位疼痛（2764例疫苗组中656例[23.7%]）、疲劳（2764例中551例[19.9%]）、头痛（2765例中498例[18.0%]）和肌痛（2764例中486例[17.6%]）。

发现:支持这种疫苗保护12-64岁人群免受基孔肯雅病毒引起的疾病的潜力。

研究结果表明，Vimkunya诱导快速和强大的免疫反应。这些发现支持了这种疫苗保护12-64岁人群免受基孔肯雅病毒引起的疾病的潜力。

附：英文原文

Title: Chikungunya virus virus-like particle vaccine safety and immunogenicity in adolescents and adults in the USA: a phase 3, randomised, double-blind, placebo-controlled trial

Author: Jason S Richardson, Deborah M Anderson, Jason Mendy, Lauren C Tindale, Sufia Muhammad, Tobi Loreth, Sarah Royalty Tredo, Kelly L Warfield, Roshan Ramanathan, Jorge T Caso, Victoria A Jenkins, Patrick Ajiboye, Lisa Bedell

Issue&Volume: 2025-03-27

Abstract: Background

Chikungunya disease is a growing global public health concern. Vimkunya (previously chikungunya virus virus-like particle vaccine, previously PXVX0317) is a single-dose, pre-filled syringe for intramuscular injection. Here, we report safety, tolerability, and immunogenicity data for Vimkunya versus placebo in healthy adolescents and adults aged 12–64 years, and evaluate lot-to-lot consistency.

Methods

This pivotal phase 3, randomised, double-blind, placebo-controlled, parallel-group trial was done at 47 clinical trial sites in the USA. Eligible participants were healthy adolescents and adults aged 12–64 years. Participants were divided into three age strata (12–17 years, 18–45 years, and 46–64 years) within each site and randomly assigned (2:2:2:1) to receive one of three consecutively manufactured lots of Vimkunya or placebo (same excipient composition without chikungunya virus virus-like particle or aluminium hydroxide components) on study day 1. Neither participants, nor clinical site personnel, nor the funder knew participants' individual treatment assignments until all participants completed their involvement in the trial and the database was cleaned and locked. Participants attended a screening visit, followed by a day 1 visit that included random assignment, blood sample collection, and administration of a single dose of Vimkunya or placebo by intramuscular injection in the deltoid muscle. The coprimary endpoints were: the difference in chikungunya virus serum neutralising antibody seroreponse rate (vaccine minus placebo) at day 22; chikungunya virus serum neutralising antibody geometric mean titre (GMT) at day 22 for vaccine and placebo; and chikungunya virus serum neutralising GMT ratio at day 22 between all three pairs of vaccine lots (A:B, B:C, and A:C) in adults aged 18–45 years. The trial is registered with ClinicalTrials.gov, NCT05072080 and EudraCT, 2023-001124-42.

Findings

Between Sept 29, 2021, and Sept 23, 2022, 4215 participants were screened, of whom 3258 were eligible and enrolled (1667 [51·2%] female and 1591 [48·8%] male), and 3254 (99·9%) received either Vimkunya (n=2790) or placebo (n=464). The immunogenicity evaluable population included 2983 participants, of whom 2559 received Vimkunya and 424 received placebo. At day 22, 2503 (97·8%) of 2559 participants in the Vimkunya group had a seroresponse, compared with five (1·2%) of 424 participants in the placebo group for the immunogenicity evaluable population. The seroreponse rate difference was 96·6% (95% CI 95·0–97·5; p<0·0001). In the immunogenicity evaluable population, chikungunya virus serum neutralising antibody GMT at day 22 for the vaccine group was 1618 and for the placebo group was 7·9 (p<0·0001). At day 22, the serum neutralising GMT ratios for the pairs of lots (A:B, B:C, and A:C) were 0·98 (95% CI 0·85–1·14), 0·97 (0·84–1·12), and 0·95 (0·82–1·10), respectively. Vimkunya had a favourable safety profile; most adverse events were self-limiting and grade 1 or 2 in severity. The most common adverse events were injection site pain (656 [23·7%] of 2764 participants in the vaccine group), fatigue (551 [19·9%] of 2764), headache (498 [18·0%] of 2765), and myalgia (486 [17·6%] of 2764).

Interpretation

Vimkunya induces a rapid and robust immune response. These findings support the potential for this vaccine to protect individuals aged 12–64 years from disease caused by chikungunya virus.

DOI: 10.1016/S0140-6736(25)00345-9

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(25)00345-9/abstract