Skip to main page content
U.S. flag

An official website of the United States government

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2021 Aug;8(15):e2002751.
doi: 10.1002/advs.202002751. Epub 2021 Jun 3.

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

Xiaowei Xu  1 , Rui Yu  2 , Lanlan Xiao  1 , Jie Wang  1 , Meihong Yu  1 , Junjie Xu  2 , Yajun Tan  3 , Xiao Ma  3 , Xiaoxin Wu  1 , Jiangshan Lian  1 , Kaizhou Huang  1 , Xiaoxi Ouyang  1 , Sheng Bi  1 , Shipo Wu  2 , Xiaoyan Wang  1 , Jiandi Jin  1 , Ling Yu  1 , Huafen Zhang  1 , Qi Wei  4 , Jinfa Shi  4 , Wei Chen  2 , Lanjuan Li  1
Affiliations
Clinical Trial

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

Xiaowei Xu et al. Adv Sci (Weinh). 2021 Aug.

Abstract

Tetanus 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.

Keywords: recombinant tetanus vaccine; tetanus; tetanus toxoid vaccine.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Trial profiles of the initial study and the booster study. TT = tetanus toxoid.
Figure 2
Figure 2
Proportion of seroconversion of anti‐TT IgG or anti‐TeNT‐Hc IgG antibodies 28 days after each vaccination (A). Proportion of seroconversion of anti‐TT IgG antibody (B). Proportion of seroconversion of anti‐TeNT‐Hc IgG antibody. Seroconversion, defined as a four‐time rise in antibody titer compared with baseline titer (baseline titer ≥50), or titer ≥ 200 (baseline titer <50), 4 weeks after each vaccination. TT = tetanus toxoid.
Figure 3
Figure 3
Geometric mean titer of anti‐TT or anti‐TeNT‐Hc IgG antibody, after initial and booster vaccination (A). Geometric mean titer of anti‐TT IgG antibody (B). Geometric mean titer of anti‐TeNT‐Hc IgG antibody. p values were generated by comparing the positive vaccine and all doses of the recombinant tetanus vaccine, the data were compared using Wilcoxon rank sum test. TT = tetanus toxoid.
Figure 4
Figure 4
Specific T‐cell response measured by enzyme‐linked immunosorbent spot (ELISPOT) assay at different time points before and after prime and booster vaccination. A) IL‐2 expressing T‐cells, number of ELISPOT spot forming cells (SFC)/10⁶ cells. B) IFN‐γ expressing T cells, number of ELISPOT SFC/10⁶ cells. TT = tetanus toxoid.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Yen L. M., Thwaites C. L, Lancet 2019, 393, 1657. - PubMed
    1. Beeching N. J., Crowcroft N. S, BMJ 2005, 330, 208. - PMC - PubMed
    1. Filia A., Bella A., von Hunolstein C., Pinto A., Alfarone G., Declich S., Rota M. C, Vaccine 2014, 32, 639. - PubMed
    1. Kyu H. H., Mumford J. E., Stanaway J. D., Barber R. M., Hancock J. R., Vos T., Murray C. J., Naghavi M., BMC Public Health 2017, 17, 179. - PMC - PubMed
    1. Rodrigo C., Fernando D., Rajapakse S., Crit. Care 2014, 18, 217. - PMC - PubMed

Publication types