Duc Le H, Hong Huynh A, Fairweather Neil, Ricca Ezio, Cutting Simon M
School of Biological Sciences, Royal Holloway University of London, Egham, Surrey TW20 0EX, United Kingdom.
Infect Immun. 2003 May;71(5):2810-8. doi: 10.1128/IAI.71.5.2810-2818.2003.
For the first time, bacterial spores have been evaluated as vaccine vehicles. Bacillus subtilis spores displaying the tetanus toxin fragment C (TTFC) antigen were used for oral and intranasal immunization and were shown to generate mucosal and systemic responses in a murine model. TTFC-specific immunoglobulin G titers in serum (determined by enzyme-linked immunosorbent assay) reached significant levels 33 days after oral dosing, while responses against the spore coat proteins were relatively low. Tetanus antitoxin levels were sufficient to protect against an otherwise lethal challenge of tetanus toxin (20 50% lethal doses). The robustness and long-term storage properties of bacterial spores, coupled with simplified genetic manipulation and cost-effective manufacturing, make them particularly attractive vehicles for oral and intranasal vaccination.
细菌孢子首次被评估用作疫苗载体。展示破伤风毒素片段C(TTFC)抗原的枯草芽孢杆菌孢子被用于口服和鼻内免疫,并在小鼠模型中显示可产生黏膜和全身反应。口服给药33天后,血清中TTFC特异性免疫球蛋白G滴度(通过酶联免疫吸附测定法测定)达到显著水平,而针对芽孢衣蛋白的反应相对较低。破伤风抗毒素水平足以抵御否则会致命的破伤风毒素攻击(20个50%致死剂量)。细菌孢子的稳健性和长期储存特性,再加上简化的基因操作和具有成本效益的生产,使其成为口服和鼻内疫苗接种特别有吸引力的载体。