背景:莱姆病,可能与严重的长期并发症有关,是由复杂的伯氏疏螺旋体引起的。我们研究了一种新颖的莱姆病疏螺旋体病候选疫苗(VLA15),该疫苗针对六种最常见的外表面蛋白A(OspA)血清型1-6,以防止在欧洲和北美流行的致病性疏螺旋体感染。
方法:这是部分随机的,观察者面具,在比利时和美国的试验中心,对18岁以上至40岁以下的健康成年人(n=179)进行了1期研究。在非随机磨合阶段之后,采用1:1:1:1:1:1的密封包膜随机化方法;三种剂量浓度的VLA15(12μg,48μg,和90μg)在第1、29和57天通过肌肉注射给药。主要结果是在接受至少一次疫苗接种的参与者中评估的安全性(直到第85天的不良事件频率)。免疫原性是次要结果。该试验已在ClinicalTrials.gov注册,NCT03010228,完成。
结果:在2017年1月23日至2019年1月16日之间,对254名参与者进行了资格筛选,179个被随机分为六组:明矾佐剂12μg(n=29),48μg(n=31),或90μg(n=31)和非佐剂化12μg(n=29名参与者),48μg(n=29),或90μg(n=30)。VLA15安全且耐受性良好,大多数不良事件为轻度或中度。总的来说,与12μg组(25[86%]参与者相比,48μg和90μg组(范围28-30名参与者[94-97%])中的不良事件更频繁,95%CI69·4-94·5),用于佐剂化和非佐剂化基团。常见的局部反应是压痛(151例[84%]参与者;356例事件,95%CI78·3-89·4)和注射部位疼痛(120[67%];224起事件,59·9-73·5);最常见的全身反应是头痛(80[45%];112起事件,37·6-52·0),过度疲劳(45[25%];56个事件,19·4-32·0),和肌痛(45[25%];57个事件,19·4-32·0)。在佐剂化和非佐剂化的制剂之间观察到类似的安全性和耐受性特征。大多数征求的不良事件为轻度或中度。VLA15对所有OspA血清型均具有免疫原性,在佐剂高剂量组中诱导了更高的免疫反应(几何平均滴度范围为90μg,明矾61·3U/mL-321·7U/mL与23·8U/mL-111·5U/mL,90μg无明矾)。
结论:这种针对莱姆病的新型多价候选疫苗是安全和免疫原性的,为进一步的临床开发铺平了道路。
背景:Valneva奥地利.
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.