在一项在布基纳法索儿童中进行的盲法、随机、对照、年龄递减的 Ib 期临床试验中，BK-SE36 的安全性和免疫原性。
Safety and immunogenicity of BK-SE36 in a blinded, randomized, controlled, age de-escalating phase Ib clinical trial in Burkinabe children.
机构信息
Groupe de Recherche Action en Santé, Ouagadougou (GRAS), Ouagadougou, Burkina Faso.
Centre National de Recherche et de Formation sur le Paludisme (CNRFP), Ouagadougou, Burkina Faso.
出版信息
Front Immunol. 2022 Aug 31;13:978591. doi: 10.3389/fimmu.2022.978591. eCollection 2022.
BACKGROUND
A blood-stage vaccine targeting the erythrocytic-stages of the malaria parasite could play a role to protect against clinical disease. Antibodies against the serine repeat antigen 5 (SE47 and SE36 domains) correlate well with the absence of clinical symptoms in sero-epidemiological studies. A previous phase Ib trial of the recombinant SE36 antigen formulated with aluminum hydroxyl gel (BK-SE36) was promising. This is the first time the vaccine candidate was evaluated in young children below 5 years using two vaccination routes.
METHODS
Safety and immunogenicity of BK-SE36 was assessed in a double-blind, randomized, controlled, age de-escalating phase Ib trial. Fifty-four Burkinabe children in each age cohort, 25-60 or 12-24 months, were randomized in a 1:1:1 ratio to receive three doses of BK-SE36 either by intramuscular (BK IM) or subcutaneous (BK SC) route on Day 0, Week 4, and 26; or the control vaccine, Synflorix IM route on Day 0, Week 26 (and physiological saline on Week 4). Safety data and samples for immunogenicity analyses were collected at various time-points.
RESULTS
Of 108 subjects, 104 subjects (96.3%) (Cohort 1: 94.4%; Cohort 2: 98.1%) received all three scheduled vaccine doses. Local reactions, mostly mild or of moderate severity, occurred in 99 subjects (91.7%). The proportion of subjects that received three doses without experiencing Grade 3 adverse events was similar across BK-SE36 vaccines and control arms (Cohort 1: 100%, 89%, and 89%; and Cohort 2: 83%, 82%, and 83% for BK IM, BK SC, and control, respectively). BK-SE36 vaccine was immunogenic, inducing more than 2-fold change in antibody titers from pre-vaccination, with no difference between the two vaccination routes. Titers waned before the third dose but in both cohorts titers were boosted 6 months after the first vaccination. The younger cohort had 2-fold and 4-fold higher geometric mean titers compared to the 25- to 60-month-old cohort after 2 and 3 doses of BK-SE36, respectively.
CONCLUSION
BK-SE36 was well tolerated and immunogenic using either intramuscular or subcutaneous routes, with higher immune response in the younger cohort.
CLINICAL TRIAL REGISTRATION
https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=934, identifier PACTR201411000934120.
背景
针对疟原虫红细胞期的血阶段疫苗可能在预防临床疾病方面发挥作用。在血清流行病学研究中，针对丝氨酸重复抗原 5（SE47 和 SE36 结构域）的抗体与无临床症状密切相关。此前，使用铝羟凝胶（BK-SE36）配制的重组 SE36 抗原的 I 期 b 试验结果令人鼓舞。这是该候选疫苗首次在 5 岁以下的儿童中通过两种接种途径进行评估。
方法
在一项双盲、随机、对照、年龄递减的 I 期 b 试验中，评估了 BK-SE36 的安全性和免疫原性。每个年龄组 54 名布基纳法索儿童（25-60 或 12-24 个月）按 1:1:1 的比例随机分配，分别通过肌肉内（BK IM）或皮下（BK SC）途径在第 0 天、第 4 天和第 26 天接受 3 剂 BK-SE36；或对照疫苗，Synflorix 肌肉内途径在第 0 天，第 26 天（第 4 天生理盐水）。在不同时间点收集安全性数据和免疫原性分析样本。
结果
108 名受试者中，104 名（96.3%）（队列 1：94.4%；队列 2：98.1%）接受了所有 3 次计划疫苗接种。99 名受试者（91.7%）出现局部反应，多为轻度或中度严重程度。在没有发生 3 级不良事件的情况下，接受 3 剂疫苗的受试者比例在 BK-SE36 疫苗和对照组之间相似（队列 1：100%、89%和 89%；队列 2：83%、82%和 83%，分别为 BK IM、BK SC 和对照）。BK-SE36 疫苗具有免疫原性，抗体滴度较接种前增加 2 倍以上，两种接种途径之间无差异。在第三剂之前滴度下降，但在两个队列中，在第一次接种后 6 个月时滴度均有所升高。与 25-60 个月龄队列相比，较小的队列在接受 2 剂和 3 剂 BK-SE36 后，几何平均滴度分别高出 2 倍和 4 倍。
结论
BK-SE36 经肌肉内或皮下途径给药具有良好的耐受性和免疫原性，在较小的队列中具有更高的免疫反应。
临床试验注册
https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=934，标识符 PACTR201411000934120。
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