在健康成年人中，以Montanide ISA 720配制的疟疾疫苗恶性疟原虫AMA-1/MSP-1嵌合蛋白的安全性和免疫原性。
Safety and immunogenicity of a malaria vaccine, Plasmodium falciparum AMA-1/MSP-1 chimeric protein formulated in montanide ISA 720 in healthy adults.
作者信息
Hu Jinhong, Chen Zhihui, Gu Jun, Wan Mobin, Shen Qian, Kieny Marie-Paule, He Jia, Li Zhen, Zhang Qingfeng, Reed Zarifah Hussain, Zhu Yongmei, Li Wenjie, Cao Yang, Qu Li, Cao Zhifang, Wang Qiang, Liu Haitao, Pan Xuegong, Huang Xiudong, Zhang Dongmei, Xue Xiangyang, Pan Weiqing
机构信息
Changhai Hospital, Second Military Medical University, Shanghai, China.
出版信息
PLoS One. 2008 Apr 9;3(4):e1952. doi: 10.1371/journal.pone.0001952.
BACKGROUND
The P. falciparum chimeric protein 2.9 (PfCP-2.9) consisting of the sequences of MSP1-19 and AMA-1 (III) is a malaria vaccine candidate that was found to induce inhibitory antibodies in rabbits and monkeys. This was a phase I randomized, single-blind, placebo-controlled, dose-escalation study to evaluate the safety and immunogenicity of the PfCP-2.9 formulated with a novel adjuvant Montanide ISA720. Fifty-two subjects were randomly assigned to 4 dose groups of 10 participants, each receiving the test vaccine of 20, 50, 100, or 200 microg respectively, and 1 placebo group of 12 participants receiving the adjuvant only.
METHODS AND FINDINGS
The vaccine formulation was shown to be safe and well-tolerated, and none of the participants withdrew. The total incidence of local adverse events (AEs) was 75%, distributed among 58% of the placebo group and 80% of those vaccinated. Among the vaccinated, 65% had events that were mild and 15% experienced moderate AEs. Almost all systemic adverse reactions observed in this study were graded as mild and required no therapy. The participants receiving the test vaccine developed detectable antibody responses which were boosted by the repeated vaccinations. Sixty percent of the vaccinated participants had high ELISA titers (>1:10,000) of antigen-specific antibodies which could also recognize native parasite proteins in an immunofluorescence assay (IFA).
CONCLUSION
This study is the first clinical trial for this candidate and builds on previous investigations supporting PfCP-2.9/ISA720 as a promising blood-stage malaria vaccine. Results demonstrate safety, tolerability (particularly at the lower doses tested) and immunogenicity of the formulation. Further clinical development is ongoing to explore optimizing the dose and schedule of the formulation to decrease reactogenicity without compromising immunogenicity.
TRIAL REGISTRATION
Chinese State Food and Drug Administration (SFDA) 2002SL0046; Controlled-Trials.com ISRCTN66850051 [66850051].
背景
由疟原虫裂殖子表面蛋白1（MSP1）-19和裂殖体表面蛋白AMA-1（III）序列组成的恶性疟原虫嵌合蛋白2.9（PfCP-2.9）是一种疟疾疫苗候选物，已发现其能在兔和猴体内诱导产生抑制性抗体。这是一项I期随机、单盲、安慰剂对照、剂量递增研究，旨在评估用新型佐剂Montanide ISA720配制的PfCP-2.9的安全性和免疫原性。52名受试者被随机分为4个剂量组，每组10名参与者，分别接受20、50、100或200微克的试验疫苗，以及1个安慰剂组，12名参与者仅接受佐剂。
方法和结果
疫苗制剂显示安全且耐受性良好，没有参与者退出。局部不良事件（AE）的总发生率为75%，安慰剂组为58%，接种疫苗者为80%。在接种疫苗者中，65%的人出现轻度事件，15%的人经历中度AE。本研究中观察到的几乎所有全身不良反应均为轻度，无需治疗。接受试验疫苗的参与者产生了可检测到的抗体反应，重复接种可增强这些反应。60%的接种参与者具有高ELISA滴度（>1:10,000）的抗原特异性抗体，这些抗体在免疫荧光试验（IFA）中也能识别天然寄生虫蛋白。
结论
本研究是该候选疫苗的首次临床试验，建立在先前支持PfCP-2.9/ISA720作为有前景的血液期疟疾疫苗的研究基础之上。结果证明了该制剂的安全性、耐受性（特别是在测试的较低剂量下）和免疫原性。正在进行进一步的临床开发，以探索优化制剂的剂量和接种程序，在不影响免疫原性的情况下降低反应原性。
试验注册
中国国家食品药品监督管理总局（SFDA）2002SL0046；Controlled-Trials.com ISRCTN66850051 [66850051]。
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