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热稳定的藻类口服疫苗可保护小鼠免受金黄色葡萄球菌感染。

Heat-stable oral alga-based vaccine protects mice from Staphylococcus aureus infection.

机构信息

Department of Biosystems Science and Engineering, ETH Zurich, Mattenstrasse 26, CH-4058 Basel, Switzerland.

出版信息

J Biotechnol. 2010 Feb 1;145(3):273-80. doi: 10.1016/j.jbiotec.2009.12.006. Epub 2009 Dec 6.

Abstract

While 15 million deaths per year are caused by communicable pathogens worldwide, health care authorities emphasize the considerable impact of poverty on the incidence of infectious diseases. The emergence of antigen-expressing plant tissues (e.g. rice, tomato, potato) has indicated the potential of land plants for low-cost vaccines in oral immunization programs. In this study, we engineered the chloroplasts of the unicellular green alga Chlamydomonas reinhardtii for the stable expression of the D2 fibronectin-binding domain of Staphylococcus aureus fused with the cholera toxin B subunit (CTB), under the control of rbcL UTRs. Analysis of sera and faeces of mice, fed for 5 weeks with transgenic algae grown in confined Wave Bioreactor, revealed the induction of specific mucosal and systemic immune responses. Algae-based vaccination significantly reduced the pathogen load in the spleen and the intestine of treated mice and protected 80% of them against lethal doses of S. aureus. Importantly, the alga vaccine was stable for more than 1.5 years at room temperature. These results indicate that C. reinhardtii may play an important role in molecular pharming, as it combines the beneficial features of land plant vaccines, while offering unmatched ease of growth compared to other members of the plant kingdom.

摘要

虽然每年有 1500 万人死于全球传播病原体,但卫生保健当局强调贫困对传染病发病率的巨大影响。表达抗原的植物组织(如水稻、番茄、土豆)的出现表明,陆地植物有可能成为口服免疫接种计划中低成本疫苗的来源。在这项研究中,我们对单细胞绿藻莱茵衣藻的叶绿体进行了工程改造,使其在 RBCL UTR 的控制下稳定表达与霍乱毒素 B 亚单位(CTB)融合的金黄色葡萄球菌 D2 纤维连接蛋白结合域。对用在限定波生物反应器中生长的转基因藻类喂养 5 周的小鼠的血清和粪便进行分析,揭示了诱导特定黏膜和全身免疫反应。藻类疫苗接种显著降低了治疗小鼠脾脏和肠道中的病原体负荷,并保护了 80%的小鼠免受金黄色葡萄球菌致死剂量的侵害。重要的是,这种藻类疫苗在室温下可稳定保存 1.5 年以上。这些结果表明,莱茵衣藻可能在分子制药中发挥重要作用,因为它结合了陆地植物疫苗的有益特征,同时与植物王国的其他成员相比,具有无与伦比的生长优势。

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