Emergent BioSolutions, Gaithersburg, MD, USA.
Stanford University School of Medicine, Stanford, CA, USA.
Lancet Infect Dis. 2022 Sep;22(9):1343-1355. doi: 10.1016/S1473-3099(22)00226-2. Epub 2022 Jun 13.
Chikungunya virus (CHIKV) disease is an ongoing public health threat. We aimed to evaluate the safety and immunogenicity of PXVX0317, an aluminium hydroxide-adjuvanted formulation of a CHIKV virus-like particle (VLP) vaccine.
This randomised, double-blind, parallel-group, phase 2 trial was conducted at three clinical trial centres in the USA. Eligible participants were healthy CHIKV-naïve adults aged 18-45 years. Participants were stratified by site and randomly assigned (1:1:1:1:1:1:1:1) to one of the eight vaccination groups using a block size of 16. Group 1 received two doses of unadjuvanted PXVX0317 28 days apart (2 × 20 μg; standard); all other groups received adjuvanted PXVX0317: groups 2-4 received two doses 28 days apart (2 × 6 μg [group 2], 2 × 10 μg [group 3], or 2 × 20 μg [group 4]; standard); group 4 also received a booster dose 18 months after the first active injection (40 μg; standard plus booster); groups 5-7 received two doses 14 days apart (2 × 6 μg [group 5], 2 × 10 μg [group 6], or 2 × 20 μg [group 7]; accelerated); and group 8 received one dose (1 × 40 μg; single). The primary endpoint was the geometric mean titre of anti-CHIKV neutralising antibody on day 57 (28 days after the last vaccination), assessed in the immunogenicity-evaluable population. Additionally, we assessed safety. This trial is registered at ClinicalTrials.gov, NCT03483961.
This trial was conducted from April 18, 2018, to Sept 21, 2020; 468 participants were assessed for eligibility. Of these, 415 participants were randomly assigned to eight groups (n=53 in groups 1, 5, and 6; n=52 in groups 2 and 8; n=51 in groups 3 and 7; and n=50 in group 4) and 373 were evaluable for immunogenicity. On day 57, serum neutralising antibody geometric mean titres were 2057·0 (95% CI 1584·8-2670·0) in group 1, 1116·2 (852·5-1461·4; p=0·0015 vs group 1 used as a reference) in group 2, 1465·3 (1119·1-1918·4; p=0·076) in group 3, 2023·8 (1550·5-2641·7; p=0·93) in group 4, 920·1 (710·9-1190·9; p<0·0001) in group 5, 1206·9 (932·4-1562·2; p=0·0045) in group 6, 1562·8 (1204·1-2028·3; p=0·14) in group 7, and 1712·5 (1330·0-2205·0; p=0·32) in group 8. In group 4, a booster dose increased serum neutralising antibody geometric mean titres from 215·7 (95% CI 160·9-289·1) on day 547 to 10 941·1 (7378·0-16 225·1) on day 575. Durability of the immune response (evaluated in groups 1, 4, and 8) was shown up to 2 years. The most common solicited adverse event was pain at the injection site, reported in 12 (23%) of 53 participants who received the unadjuvanted vaccine (group 1) and 111 (31%) of 356 who received the adjuvanted vaccine. No vaccine-related serious adverse events were reported.
PXVX0317 was well tolerated and induced a robust and durable serum neutralising antibody immune response against CHIKV up to 2 years. A single 40 μg injection of adjuvanted PXVX0317 is being further investigated in phase 3 clinical trials (NCT05072080 and NCT05349617).
Emergent BioSolutions.
基孔肯雅病毒（CHIKV）疾病是当前公共卫生的一个威胁。我们旨在评估 PXVX0317 的安全性和免疫原性，PXVX0317 是一种含有基孔肯雅病毒样颗粒（VLP）的铝佐剂疫苗。
这是一项在美国三个临床试验中心进行的随机、双盲、平行分组、2 期临床试验。合格的参与者是年龄在 18-45 岁之间的健康基孔肯雅病毒初次感染的成年人。参与者按地点分层，并使用 16 的分组大小随机分配（1:1:1:1:1:1:1:1）至 8 个接种组之一。第 1 组接受两次无佐剂的 PXVX0317 接种，间隔 28 天（2×20μg；标准）；所有其他组接受佐剂 PXVX0317 接种：第 2-4 组在 28 天间隔内接受两次接种（2×6μg[第 2 组]、2×10μg[第 3 组]或 2×20μg[第 4 组]；标准）；第 4 组还在第一次主动注射后 18 个月接受加强剂量（40μg；标准加加强）；第 5-7 组在 14 天间隔内接受两次接种（2×6μg[第 5 组]、2×10μg[第 6 组]或 2×20μg[第 7 组]；加速）；第 8 组接受一次接种（1×40μg；单次）。主要终点是第 57 天（最后一次接种后 28 天）抗 CHIKV 中和抗体的几何平均滴度，在免疫原性可评估人群中进行评估。此外，我们还评估了安全性。这项试验在 ClinicalTrials.gov 上注册，编号为 NCT03483961。
这项试验于 2018 年 4 月 18 日至 2020 年 9 月 21 日进行；有 468 名参与者符合入组条件。其中，415 名参与者被随机分配至 8 个组（第 1、5 和 6 组每组 53 名参与者；第 2 和第 8 组各 52 名参与者；第 3 和第 7 组各 51 名参与者；第 4 组各 50 名参与者），373 名参与者可用于免疫原性评估。第 57 天，血清中和抗体的几何平均滴度分别为：第 1 组 2057.0（95%CI 1584.8-2670.0），第 2 组 1116.2（852.5-1461.4；p=0.0015，与第 1 组作为参考相比），第 3 组 1465.3（1119.1-1918.4；p=0.076），第 4 组 2023.8（1550.5-2641.7；p=0.93），第 5 组 920.1（710.9-1190.9；p<0.0001），第 6 组 1206.9（932.4-1562.2；p=0.0045），第 7 组 1562.8（1204.1-2028.3；p=0.14），第 8 组 1712.5（1330.0-2205.0；p=0.32）。在第 4 组中，加强剂量使血清中和抗体的几何平均滴度从第 547 天的 215.7（95%CI 160.9-289.1）增加到第 575 天的 10941.1（7378.0-16225.1）。免疫应答的持久性（在第 1、4 和 8 组中进行评估）最长可达 2 年。最常见的局部不良事件是注射部位疼痛，在接受未佐剂疫苗（第 1 组）的 53 名参与者中有 12 名（23%）和接受佐剂疫苗的 356 名参与者中有 111 名（31%）报告。没有与疫苗相关的严重不良事件报告。
PXvX0317 耐受性良好，可诱导针对 CHIKV 的强大且持久的血清中和抗体免疫应答，最长可达 2 年。在 3 期临床试验（NCT05072080 和 NCT05349617）中正在进一步研究单次 40μg 剂量的佐剂 PXVX0317。
Emergent BioSolutions。
