Safety, tolerability, and immunogenicity of SPVX02, a room temperature-stabilised tetanus-diphtheria vaccine, compared to two established tetanus-diphtheria booster vaccines: a multicentre, single-blind, randomised, first-in-human phase 1 trial in the UK

Background Cold chain requirements limit vaccine accessibility and deployment. SPVX02, is a lyophilised, fridge-free version of Tetadif tetanus-diphtheria vaccine, stable for at least 24 months at temperatures up to 30 °C. Methods This multicentre, first-in-human phase 1, single-blind, randomised clinical trial was conducted at three sites in the UK to evaluate the safety and tolerability of SPVX02 compared to existing approved tetanus-diphtheria (Td) vaccines. Healthy adults (aged 18–55 years; body-mass index (BMI) ≤32 kg/m 2 ) who had received Td vaccination ≥10 years previously were randomly assigned (1:1:1) to receive a single 0.5 mL intramuscular deltoid injection of SPVX02, Tetadif, or diTeBooster, and were followed for 28 days after vaccination. Participants and all investigatory staff were blinded to treatment allocation. Primary outcomes were incidence of unsolicited adverse events (AEs) during the trial period and incidence of predefined, solicited AEs reported in participant diaries for 7 days post-dose. Secondary outcomes were seroprotection rates and Geometric Mean titres (GMT) at day 28. Analyses were descriptive. This trial is registered with ISRCTN (ISRCTN98920861). Findings Between April 1 and September 22, 2025, 120 healthy volunteers were screened and 60 participants were enrolled at two of three sites. Demographic characteristics of participants were similar between groups. No serious adverse reactions, suspected unexpected adverse reactions, or serious adverse events occurred. 54 participants experienced mild or moderate AEs; none were severe (grade 3 or higher AEs). Reactogenicity and tolerability profiles were similar across all groups. All participants had anti-tetanus toxoid (TT) levels ≥1.0 IU/mL at Day 28. All participants in both the SPVX02 and Tetadif groups and 19 (95%) in the diTeBooster group had anti-diphtheria (DT) toxoid levels ≥0.1 IU/mL at Day 28. Interpretation Our findings suggest that SPVX02 is safe, well tolerated, with TT and DT immunogenicity similar to the two existing approved Td vaccines investigated herein. This trial provides first-in-human evidence that StablevaX technology can be used to safely reformulate an aluminium-adjuvanted vaccine stable up to 30 °C for 24 months. A phase 2/3 trial is planned, and further research will investigate temperature stability at higher temperatures, and technology application to other vaccines and biological products. Funding Innovate UK Smart Grant and Stablepharma Ltd.