Background

BK-SE36 is blood-stage malaria vaccine candidate that is undergoing clinical trials. Here, the safety and immunogenicity of BK-SE36 with a novel adjuvant, CpG-ODN(K3) (thus, BK-SE36/CpG) was assessed in a phase 1a trial in Japan.

Methods

An investigator-initiated, randomised, single-blind, placebo-controlled, dose-escalation study was conducted at Osaka University Hospital with 26 healthy malaria naïve Japanese male adults. The trial was conducted in two stages: Stage/Group 1, half-dose (n = 7 for BK-SE36/CpG and n = 3 for control) and Stage/Group 2, full-dose (n = 11 for BK-SE36/CpG and n = 5 for control). There were two intramuscular vaccinations 21 days apart for both half-dose (0.5 ml: 50 µg SE36 + 500 µg aluminum + 500 µg K3) and full-dose (1.0 ml: 100 µg SE36 + 1000 µg aluminum + 1000 µg K3). A one-year follow-up was done to monitor changes in autoimmune markers and vaccine-induced antibody response.

Results

BK-SE36/CpG was well tolerated. Vaccination site reactions were similar to those observed with BK-SE36. During the trial and follow-up period, no subject had clinical evidence of autoimmune disease. The full-dose group had significantly higher titres than the half-dose group (Student’s t-test, p = 0.002) at 21 days post-second vaccination. Antibody titres remained above baseline values during 12 months of follow-up. The vaccine induced antibody was mostly composed of IgG1 and IgM, and recognised epitopes close to the polyserine region located in the middle of SE36.

Conclusions

BK-SE36/CpG has an acceptable safety profile. Use of CpG-ODN(K3) greatly enhanced immunogenicity in malaria naïve Japanese adults when compared to BK-SE36 alone. The utility of BK-SE36/CpG is currently under evaluation in a malaria endemic setting in West Africa.

Trial Registration. JMACCT Clinical Trial Registry JMA-IIA00109.

中文翻译：

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带有CpG-ODN（K3）的恶性疟原虫血液阶段疟疾疫苗BK-SE36的首次人类随机试验和随访研究

背景

BK-SE36是血液阶段疟疾疫苗的候选药物，正在接受临床试验。在日本的1a期临床试验中，评估了BK-SE36与新型佐剂CpG-ODN（K3）的安全性和免疫原性（因此，BK-SE36 / CpG）。

方法

在大阪大学医院进行了一项由研究人员发起的随机，单盲，安慰剂对照，剂量递增的研究，研究对象是26位健康的纯净日本初龄男性。该试验分两个阶段进行：阶段/第1组，半剂量（对于BK-SE36 / CpG，n = 7；对于对照，n = 3）和阶段/第2组，全剂量（对于BK-SE36，n = 11） / CpG，n = 5（对照）。半剂量（0.5 ml：50 µg SE36 + 500 µg铝+ 500 µg K3）和全剂量（1.0 ml：100 µg SE36 + 1000 µg铝+ 1000 µg K3）间隔21天进行两次肌肉注射。进行了一年的随访，以监测自身免疫标志物和疫苗诱导的抗体反应的变化。

结果

BK-SE36 / CpG的耐受性良好。疫苗接种部位的反应与BK-SE36相似。在试验和随访期间，没有受试者有自身免疫性疾病的临床证据。 在第二次接种后21天，全剂量组的滴度明显高于半剂量组（Student's t检验，p = 0.002）。在随访的12个月中，抗体滴度仍高于基线值。疫苗诱导的抗体主要由IgG1和IgM组成，并且靠近SE36中部多丝氨酸区域的识别表位。

结论

BK-SE36 / CpG具有可接受的安全性。与单独使用BK-SE36相比，使用CpG-ODN（K3）可以大大提高日本初治疟疾成年人的免疫原性。目前正在西非疟疾流行地区评估BK-SE36 / CpG的效用。

试用注册。JMACCT临床试验注册中心JMA-IIA00109。