Safety, tolerability and immunogenicity of SPVX02, a room temperature-stabilised Tetanus-Diphtheria vaccine compared to Tetadif and diTeBooster: a multicentre, phase 1, blinded, randomised clinical trial

Summary Background Cold chain requirements limit vaccine accessibility and deployment. SPVX02 (Stablepharma Ltd), is a lyophilised, fridge-free version of Tetadif (BB-NCIPD EAD) tetanus-diphtheria vaccine, stable for at least 18 months at temperatures up to 30°C. Methods A multicentre, first-in-human phase 1, blinded, randomised clinical trial to evaluate the safety and tolerability of SPVX02 compared to existing approved tetanus-diphtheria (Td) vaccines was conducted. Healthy adults aged 18-55 (BMI <=32 kg/m 2 ) who had received Td vaccination >=10 years previously were randomly assigned (1:1:1) to receive SPVX02, Tetadif, or diTeBooster (AJ Vaccines A/S). Participants and all investigatory staff were blinded to treatment allocation. Primary outcomes were incidence of adverse events during the trial period including incidence of adverse events reported in participant diaries for 7 days post-dose. Secondary outcomes were day 28 seroprotection rates. Analyses were descriptive. The trial is registered with ISRCTN (98920861). Findings Between April 1st and September 22nd, 2025, 120 healthy volunteers were screened and sixty participants enrolled at two of three sites. The demographic characteristics of participants were equivalent between groups. No serious adverse reactions, suspected unexpected adverse reactions, or serious adverse events occurred. Fifty-four participants experienced mild or moderate adverse events (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 SPVX02 is safe, well tolerated, with TT and DT immunogenicity similar to approved Td vaccines. This trial provides first-in-human evidence that StablevaX (Stablepharma, UK) technology can safely reformulate an aluminium-adjuvanted vaccine stable up to 30°C for 18 months. Funding Funded by Innovate UK Smart Grant project #10083165 and Stablepharma Ltd. Research In Context Evidence before this study We searched PubMed for randomised controlled trials with thermostable vaccines between database inception and June 2024 using the terms (“temperature stable”) OR (“thermostable”) AND (“vaccin*”) OR (“thermostable vaccine”) with no language restrictions. We identified 33 publications which described various in vitro and in vivo studies that have been performed by researchers as part of their efforts to develop thermostable vaccines. We also identified 2 publications which described randomised, controlled clinical trials that were conducted with thermostable vaccines; (1) a phase 2 clinical trial with ROTASIL, an oral rotavirus vaccine (Isanaka et al, NEJM, 2017) which is now licenced and distributed as a refrigerated product that must be stored but must be stored at 2-8°C; and (2) a phase 1 clinical trial with a current unapproved TB vaccine candidate, ID93+GLE-SE (Sagawa et al, Nature Comms, 2023) where there is no current public information regarding vaccine tolerance to freezing. Added value of this study This first in human study demonstrates that the reformulated thermostable aluminium hydroxide adjuvanted tetanus-diphtheria vaccine, SPVX02, is safe, well tolerated, and can boost immune responses to tetanus and diphtheria to similar levels as approved comparator vaccines. This vaccine can be stored and distributed at room temperature and is not affected by freezing. A larger Phase 2/3 trial is now planned to confirm these findings prior to consideration for market authorisation. Implications of all the available evidence The evidence presented here demonstrates that StablevaX technology can be successfully utilised to reformulate a vaccine to be thermostable at room temperature for an extended period of time, without compromising reactogenicity or immunogenicity. While we present data pertaining to a single vaccine, the reformulation and lyophilisation technology underpinning SPVX02 can be applied to many liquid vaccines and biological products. The WHO Immunization Agenda 2030 sets out the global strategy to improve vaccine access in resource-limited settings, prevent vaccine wastage and to reduce the logistical, financial and environmental impact of cold chain requirements. If proven successful across a broader range of vaccine products this technology has potential to significantly benefit global health.