Safety and Immunogenicity of Single-Dose of Adsorbed Tetanus Vaccine in Adults Aged 18-44 Years: Randomized, Double-Blind, Positive-Controlled Phase I/III Clinical Trial.

Abstract

Background: The persistence of non-neonatal tetanus (non-NT) highlights the necessity of adult booster vaccines and post-traumatic prophylaxis. This Phase I/III clinical trial aimed to evaluate the safety and immunogenicity of a new adsorbed tetanus vaccine. Methods: A randomized, double-blind, positive-controlled clinical trial was conducted in Henan Province, China. A total of 1258 healthy participants aged 18-44 years (60 in Phase I and 1198 in Phase III) were enrolled, with no history of tetanus infection, or tetanus toxoid-containing vaccines (TTCVs) vaccination within the past 10 years. The participants were randomly assigned at a 1:1 ratio to receive a single dose of either the investigational vaccine or the licensed control vaccine. The Phase III clinical trial was initiated subsequent to the 7-day safety observation period following vaccination in the Phase I trial. The objective of the Phase III clinical trial was to assess the non-inferiority of the seroconversion rate of tetanus antibodies at 30 days post-vaccination with the investigational vaccine compared to the control vaccine. Serum samples were collected prior to and at 30 days post-vaccination. Adverse events were monitored for 30 days, with serious adverse events (SAEs) followed up for 6 months post-vaccination. Results: The investigational group achieved a seroconversion rate of 99.48%, which was non-inferior to that of the control group (99.66%), with a negligible rate difference of -0.17% (95% confidence interval [CI]: -1.20%, 0.78%). The investigational group exhibited a significantly higher geometric mean concentration (GMC) of antibodies (4.721 IU/mL vs. 3.627 IU/mL, p < 0.0001). Among the susceptible participants, the seroconversion rates were 99.78% in the investigational group and 99.79% in the control group, respectively, with a non-inferior rate difference of -0.01% (95%CI: -1.06%, 0.97%). Furthermore, the investigational group showed a low incidence of adverse reactions (ARs) within 30 days post-vaccination (12.26%), which was comparable to that of the control group (13.65%). All the reported ARs were mild or moderate, and no SAEs were associated with the vaccination. Conclusions: The new adsorbed tetanus vaccine demonstrated favorable safety and comparable immunogenicity to the marketed control vaccine, with a significantly higher antibody GMC, supporting its clinical application in tetanus prevention.