Valneva Austria, Campus Vienna Biocenter 3, Vienna, Austria.
Assign Data Management and Biostatistics, Innsbruck, Austria.
Lancet Infect Dis. 2023 Oct;23(10):1186-1196. doi: 10.1016/S1473-3099(23)00210-4. Epub 2023 Jul 4.
Lyme borreliosis, potentially associated with serious long-term complications, is caused by the species complex Borrelia burgdorferi sensu lato. We investigated a novel Lyme borreliosis vaccine candidate (VLA15) targeting the six most common outer surface protein A (OspA) serotypes 1-6 to prevent infection with pathogenic Borrelia spp prevalent in Europe and North America.
This was a partially randomised, observer-masked, phase 1 study in healthy adults older than 18 years to younger than 40 years (n=179) done in trial sites in Belgium and the USA. Following a non-randomised run-in phase, a sealed envelope randomisation method was applied with a 1:1:1:1:1:1 ratio; three dose concentrations of VLA15 (12 μg, 48 μg, and 90 μg) were administered by intramuscular injection on days 1, 29, and 57. The primary outcome was safety (frequency of adverse events up to day 85) assessed in participants who received at least one vaccination. Immunogenicity was a secondary outcome. The trial is registered with ClinicalTrials.gov, NCT03010228, and is complete.
Between Jan 23, 2017 and Jan 16, 2019, of 254 participants screened for eligibility, 179 were randomly assigned into six groups: alum-adjuvanted 12 μg (n=29), 48 μg (n=31), or 90 μg (n=31) and non-adjuvanted 12 μg (n=29 participants), 48 μg (n=29), or 90 μg (n=30). VLA15 was safe and well tolerated and the majority of adverse events were mild or moderate. Overall, adverse events were more frequent in the 48 μg and 90 μg groups (range 28-30 participants [94-97%]) when compared with the 12 μg group (25 [86%] participants, 95% CI 69·4-94·5) for adjuvanted and non-adjuvanted groups. Common local reactions were tenderness (151 [84%] participants; 356 events, 95% CI 78·3-89·4) and injection site pain (120 [67%]; 224 events, 59·9-73·5); most frequent systemic reactions were headache (80 [45%]; 112 events, 37·6-52·0), excessive fatigue (45 [25%]; 56 events, 19·4-32·0), and myalgia (45 [25%]; 57 events, 19·4-32·0). A similar safety and tolerability profile was observed between adjuvanted and non-adjuvanted formulations. The majority of solicited adverse events were mild or moderate. VLA15 was immunogenic for all OspA serotypes with higher immune responses induced in the adjuvanted higher dose groups (geometric mean titre range 90 μg with alum 61·3 U/mL-321·7 U/mL vs 23·8 U/mL-111·5 U/mL at 90 μg without alum).
This novel multivalent vaccine candidate against Lyme borreliosis was safe and immunogenic and paves the way to further clinical development.
Valneva Austria.
莱姆病可能与严重的长期并发症有关，由伯氏疏螺旋体亚种复合体引起。我们研究了一种针对最常见的外表面蛋白 A（OspA）6 种血清型 1-6 的新型莱姆病候选疫苗（VLA15），以预防欧洲和北美的致病性伯氏疏螺旋体属感染。
这是一项在比利时和美国试验点进行的、18 岁以上 40 岁以下健康成年人（n=179）参与的、部分随机、观察者设盲、1 期研究。在非随机入组阶段后，采用密封信封随机分组方法，1:1:1:1:1:1 比例；三种剂量浓度的 VLA15（12μg、48μg 和 90μg）分别于第 1、29 和 57 天肌肉注射。主要结局是安全性（至第 85 天的不良事件频率），在接受至少一次疫苗接种的参与者中评估。免疫原性是次要结局。该试验在 ClinicalTrials.gov 注册，NCT03010228，现已完成。
2017 年 1 月 23 日至 2019 年 1 月 16 日，254 名符合入选标准的患者中，179 名被随机分配至 6 组：铝佐剂 12μg（n=29）、48μg（n=31）或 90μg（n=31）和非铝佐剂 12μg（n=29）、48μg（n=29）或 90μg（n=30）。VLA15 安全且耐受良好，大多数不良事件为轻度或中度。总体而言，与 12μg 组（25[86%]名参与者，95%CI 69.4-94.5）相比，48μg 和 90μg 组（28-30 名参与者[94-97%]）的不良事件更常见，包括铝佐剂和非铝佐剂组。常见的局部反应是压痛（151[84%]名参与者；356 次事件，95%CI 78.3-89.4）和注射部位疼痛（120[67%]；224 次事件，59.9-73.5）；最常见的全身反应是头痛（80[45%]；112 次事件，37.6-52.0）、过度疲劳（45[25%]；56 次事件，19.4-32.0）和肌痛（45[25%]；57 次事件，19.4-32.0）。在佐剂和非佐剂制剂之间观察到相似的安全性和耐受性特征。大多数不良事件是轻度或中度的。VLA15 对所有 OspA 血清型均具有免疫原性，在佐剂较高剂量组诱导了更高的免疫应答（几何平均滴度范围为 90μg 佐剂为 61.3 U/mL-321.7 U/mL，90μg 无佐剂为 23.8 U/mL-111.5 U/mL）。
这种针对莱姆病的新型多价候选疫苗安全且具有免疫原性，为进一步的临床开发铺平了道路。
瓦莱瓦奥地利公司。
