title: Co-expression of tetanus toxin fragment C in Escherichia coli with thioredoxin and its evaluation as an effective subunit vaccine candidate.
abstract: The receptor-binding domain of tetanus toxin (THc), which mediates the binding of the toxin to the nerve cells, is a candidate subunit vaccine against tetanus. In this study one synthetic gene encoding the THc was constructed and highly expressed in Escherichia coli by co-expression with thioredoxin (Trx). The purified THc-vaccinated mice were completely protected against an active toxin challenge in mouse models of disease and the potency of two doses of THc was comparable to that of three doses of toxoid vaccine. And a solid-phase assay showed that the anti-THc sera inhibited the binding of THc or toxoid to the ganglioside GT1b as the anti-tetanus toxoid sera. Furthermore, mice were vaccinated once or twice at four different dosages of THc and a dose-response was observed in both the antibody titer and protective efficacy with increasing dosage of THc and number of vaccinations. The data presented in the report showed that the recombinant THc expressed in E. coli is efficacious in protecting mice against challenge with tetanus toxin suggesting that the THc protein may be developed into a human subunit vaccine candidate designed for the prevention of tetanus.
authors: Beijing Institute of Biotechnology, 20 Dongdajie Street, Fengtai District, Beijing 100071, PR China. yunzhouyu@163.com
authors: Yun-Zhou
authors: YZ
authors: Yu
authors: Zheng-Wei
authors: ZW
authors: Gong
authors: Yao
authors: Y
authors: Ma
authors: Shu-Ming
authors: SM
authors: Zhang
authors: Heng-Qi
authors: HQ
authors: Zhu
authors: Wen-Bing
authors: WB
authors: Wang
authors: Yun
authors: Y
authors: Du
authors: Shuang
authors: S
authors: Wang
authors: Wei-Yuan
authors: WY
authors: Yu
authors: Zhi-Wei
authors: ZW
authors: Sun
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005732:Gangliosides / Q000378:metabolism; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D016019:Survival Analysis; D013742:Tetanus / Q000401:mortality / Q000517:prevention & control*; D013744:Tetanus Toxin / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D013745:Tetanus Toxoid / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D013879:Thioredoxins / Q000378:metabolism*; D014611:Vaccination; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: D000907:Antibodies, Bacterial; D005732:Gangliosides; D010446:Peptide Fragments; D013744:Tetanus Toxin; D013745:Tetanus Toxoid; D022223:Vaccines, Subunit; C040635:tetanus toxin fragment C; D013879:Thioredoxins