Safety and Immunogenicity of a Recombinant Tetanus Vaccine in Healthy Adults in China: A Randomized, Double‐Blind, Dose Escalation, Placebo‐ and Positive‐Controlled, Phase 1/2 Trial

Q1 · MATERIALS SCIENCE

ArticleOA

Author: Yu, Ling ; Zhang, Huafen ; Huang, Kaizhou ; Xu, Junjie ; Wang, Xiaoyan ; Ma, Xiao ; Wu, Xiaoxin ; Xiao, Lanlan ; Tan, Yajun ; Yu, Meihong ; Wang, Jie ; Wu, Shipo ; Wei, Qi ; Yu, Rui ; Bi, Sheng ; Chen, Wei ; Li, Lanjuan ; Ouyang, Xiaoxi ; Lian, Jiangshan ; Shi, Jinfa ; Jin, Jiandi ; Xu, Xiaowei

AbstractTetanus is a fatal but vaccine‐preventable disease. The currently available tetanus vaccines are tetanus toxoid (TT)‐based. Although these vaccines are generally effective, challenges in vaccine development and access remain. A randomized, double‐blind, dose escalation, placebo‐ and positive‐controlled, phase 1/2 trial (ChiCTR1800015865) is performed to evaluate the safety and immunogenicity of an alternative recombinant tetanus vaccine based on the Hc domain of tetanus neurotoxin (TeNT‐Hc) in healthy adult volunteers. The primary outcome is the safety profile of the recombinant tetanus vaccine, and immunogenicity is the secondary outcome. 150 eligible participants were enrolled and randomly assigned to receive one of the three doses of recombinant tetanus vaccine (TeNT‐Hc 10/20/30 µg), TT vaccine, or placebo. The recombinant tetanus vaccine shows a good safety profile. The frequency of any solicited and unsolicited adverse events after each vaccination does not differ across the vaccine and placebo recipients. No serious treatment‐related adverse events occur. The recombinant tetanus vaccine shows strong immune responses (seroconversion rates, geometric mean titer, and antigen‐specific CD4+/CD8+ T‐cell responses), which are roughly comparable to those of the TT vaccine. In conclusion, the findings from this study support that recombinant tetanus vaccine is safe and immunogenic; thereby, it represents a novel vaccine candidate against tetanus.

16 Nov 2020·Protein & Peptide LettersQ4 · BIOLOGY

Expression and Purification of Tetanus Toxin Fragment C in Escherichia coli BL21(DE3)

Q4 · BIOLOGY

Article

Author: Xia, Xiaoyu ; Li, Jianqiang ; Zhang, Weijie ; Chai, Pengdi ; Ma, Jianzhong ; Pu, Xiuying ; Luo, Amiao ; Ge, Jun ; Su, Hui

Background: Tetanus is an infectious disease caused by Clostridium secreting tetanus toxin in anaerobic environment. The fragment C of Tetanus toxin (TTc) has been widely studied as a candidate vaccine to replace the existing tetanus toxoid vaccine.Objective:In this study, we established a simple method to purify recombinant protein TTc with ion-exchange chromatography from Escherichia coli expression systems.Methods:The TTc gene sequence was cloned into pET26b (+) vector and transferred to E. coli BL21 (DE3) for expression. The fermentation conditions (IPTG concentration, Induction temperature, Induction time) were optimized to obtain more soluble proteins. The soluble proteins were purified by Anion exchange chromatography and Cation exchange chromatography. The sequence of columns in the purification process was discussed. Finally, the stability of purified TTc protein were determined, the secondary structure of the purified TTc protein was determined by circular dichroism. The molecular weight of the purified TTc protein was determined by liquid chromatograph- mass spectrometer. Furthermore, we verified the immunogenicity of the purified protein in mice.Results: The purity of TTc improved from 34% to 88% after the first anion exchange column, and the final yield of recombinant TTc (purity > 95%) can reach 84.79% after the following cation exchange chromatography. The recombinant TTc had a molecular weight of 51.737 KDa, was stable at 4 °C and weak alkaline environment, was a β-sheet secondary structure, and had strong immunogenicity.Conclusion:The purification method we developed might be an efficient method for the industrial production of tetanus recombinant TTc vaccine.

01 Nov 2020·ToxiconQ3 · MEDICINE

Evaluation of a recombinant tetanus toxin subunit vaccine

Q3 · MEDICINE

Article

Author: Yu, Yun-Zhou ; Liu, Fu-Jia ; Shi, Dan-Yang ; Lu, Jian-Sheng ; Wang, Rong ; Li, Zhi-Ying ; Pang, Xiao-Bin ; Yang, Zhi-Xin

Tetanus is an acute, fatal disease caused by exotoxin produced by Clostridium tetani. The current vaccine against tetanus is based on inactivated tetanus toxin (TeNT). To develop a recombinant TeNT vaccine suitable for replacement of full-length tetanus toxoid (TT) vaccine for use in humans, a recombinant non-tagged isoform of the Hc domain of the tetanus toxin (THc) was expressed in Escherichia coli and purified by sequential chromatography steps. The immunogenicity and protective effect of the THc antigen were explored and compared with those of TT in Balb/c mice. The THc-based subunit vaccine provided complete protection against TeNT challenge following a high dosage as a toxoid vaccine. While the anti-THc and neutralising antibody titres were higher for the THc-based vaccine than the TT vaccine because protective epitopes are located on the THc domain. Frequency- and dose-dependent immunoprotection were also observed in THc-immunised mice. Mice immunised with one injection of 1 μg or 4 μg THc antigen were completely protected against 10² or 10³ 50% mouse lethal dose (LD₅₀) of TeNT, respectively. Furthermore, the THc protein was found to recognise and bind to ganglioside GT1b in a dose-dependent manner, and anti-THc sera antibodies also inhibited binding between THc and GT1b. Antigen on the form of recombinant non-tagged THc domain expressed in E. coli achieved strong immunoprotective potency, suggesting that it could be developed into a candidate subunit vaccine against tetanus as an alternative to the current TT vaccine.

100 Deals associated with Recombinant tetanus vaccine (Beijing Institute of Biotechnology/Sichuan ZehaTimes Pharmaceutical)

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Indication	Highest Phase	Country/Location	Organization	Date
Tetanus	Phase 2	CN	Sichuan ZehaTimes Pharmaceutical Co. Ltd.	-

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Recombinant tetanus vaccine (Beijing Institute of Biotechnology/Sichuan ZehaTimes Pharmaceutical)

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