Lee Shee Eun, Nguyen Chung Truong, Kim Soo Young, Thi Thinh Nguyen, Rhee Joon Haeng
Clinical Vaccine R&D Center, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, Korea. ; Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju, Korea.
Clinical Vaccine R&D Center, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, Korea. ; Department of Microbiology, Chonnam National University Medical School, Gwangju, Korea.
Clin Exp Vaccine Res. 2015 Jan;4(1):59-67. doi: 10.7774/cevr.2015.4.1.59. Epub 2015 Jan 30.
Recombinant subunit vaccines provide safe and targeted protection against microbial infections. However, the protective efficacy of recombinant subunit vaccines tends to be less potent than the whole cell vaccines, especially when they are administered through mucosal routes. We have reported that a bacterial flagellin has strong mucosal adjuvant activity to induce protective immune responses. In this study, we tested whether FlaB could be used as a fusion partner of subunit vaccine for tetanus.
We constructed fusion proteins consisted with tetanus toxin fragment C (TTFC), the nontoxic C-terminal portion of tetanus toxin, and a Toll-like receptor 5 agonist from Vibrio vulnificus (FlaB). Mice were intranasally administered with fusion protein and protective immune responses of the vaccinated mice were analyzed.
FlaB-TTFC recombinant protein induced strong tetanus-specific antibody responses in both systemic and mucosal compartments and prolonged the survival of mice after challenge with a supra-lethal dose of tetanus toxin.
This study establishes FlaB as a successful fusion partner for recombinant subunit tetanus vaccine applicable through mucosal route, and it further endorses our previous observations that FlaB could be a stable adjuvant partner for mucosal vaccines.
重组亚单位疫苗可为抵抗微生物感染提供安全且有针对性的保护。然而,重组亚单位疫苗的保护效力往往比全细胞疫苗弱,尤其是通过黏膜途径给药时。我们曾报道一种细菌鞭毛蛋白具有强大的黏膜佐剂活性,可诱导保护性免疫反应。在本研究中,我们测试了FlaB是否可用作破伤风亚单位疫苗的融合伴侣。
我们构建了由破伤风毒素片段C(TTFC,破伤风毒素的无毒C末端部分)和创伤弧菌的Toll样受体5激动剂(FlaB)组成的融合蛋白。对小鼠进行鼻腔内融合蛋白给药,并分析接种疫苗小鼠的保护性免疫反应。
FlaB-TTFC重组蛋白在全身和黏膜部位均诱导了强烈的破伤风特异性抗体反应,并延长了小鼠在接受超致死剂量破伤风毒素攻击后的存活时间。
本研究证实FlaB是可通过黏膜途径应用的重组亚单位破伤风疫苗的成功融合伴侣,并且进一步支持了我们之前的观察结果,即FlaB可能是黏膜疫苗的稳定佐剂伴侣。