Vaccine-preventable diseases continue to represent a significant global public health burden. However, the requirement to maintain vaccines within a strictly controlled cold chain remains a major barrier to effective vaccine deployment and accessibility, particularly in regions with limited or fragile healthcare infrastructure. Most whole pathogen and subunit vaccines require storage at 2°C to 8°C, while some nucleic acid-based vaccines require storage at temperatures as low as -60°C to -80°C. Breaks in the cold chain during storage and transportation can result in degradation due to overheating or freezing, leading to substantial vaccine wastage. In addition to logistical challenges, cold chain infrastructure contributes to the environmental burden of vaccination programmes through energy consumption and associated greenhouse gas emissions.
Lyophilisation (freeze-drying) is an established approach used to enhance the thermal stability of pharmaceutical products, including vaccines. However, currently marketed lyophilised vaccines typically continue to require refrigerated storage and often necessitate the separate storage of a liquid diluent, thereby limiting the potential benefits of this approach in reducing cold chain dependence.
Tetanus and diphtheria are serious bacterial infections associated with significant morbidity and mortality, which are largely preventable through vaccination. Despite global immunisation efforts, gaps in vaccine coverage persist. For tetanus, a substantial number of women and newborns remain unprotected worldwide, and maternal and neonatal tetanus continues to contribute to avoidable mortality. Diphtheria similarly remains associated with a clinically significant mortality risk, particularly in settings with inadequate immunisation coverage.
Tetadif® (BB-NCIPD EAD, Sofia, Bulgaria) is a World Health Organization (WHO)-prequalified, aluminium hydroxide-adjuvanted combined tetanus and diphtheria (Td) vaccine with a well-established safety and immunogenicity profile. As a liquid formulation, Tetadif requires storage at 2°C to 8°C and is susceptible to degradation upon freezing.
SPVX02 (StablevaX™, Stablepharma Ltd., Bristol, United Kingdom) is a reformulated, lyophilised version of Tetadif designed to eliminate reliance on the cold chain. SPVX02 contains the same active components and adjuvant as the parent formulation, with the addition of excipients to enable stabilisation during lyophilisation. The resulting product can be stored at temperatures not exceeding 30°C and remains stable through multiple freeze–thaw cycles.
Preclinical studies have demonstrated that SPVX02 maintains antigen integrity, immunogenicity, and potency following prolonged storage at elevated temperatures. From a practical perspective, SPVX02 is reconstituted with water for injection immediately prior to administration, eliminating the need for a separately stored diluent.
Following receipt of scientific advice from the European Medicines Agency (EMA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA), and the successful completion of a Phase 1 first-in-human clinical trial (
https://www.medrxiv.org/content/10.64898/2026.03.09.26347956v1(si apre in una nuova finestra)) further clinical development of SPVX02 is ongoing. This European Innovation Council (EIC)-funded project supports the continued development of SPVX02 through the: (a) Good Manufacturing Practice (GMP) manufacture and batch release of clinical trial material; and (b) Conduct of a pivotal, confirmatory, Phase 2b clinical trial to evaluate the tolerability, and immunogenicity of SPVX02 against Tetadif.
The Phase 2b clinical trial will enrol approximately 160 healthy adult participants at a single clinical research site in the United Kingdom. The study will evaluate the tolerability and immune responses to SPVX02 compared with Tetadif. Participants will provide written informed consent prior to enrolment, and the study will be conducted in accordance with applicable regulatory and ethical requirements, including review and approval by an independent Research Ethics Committee and the MHRA, and registration in a public clinical trials registry.
This Phase 2b clinical trial will build on the results of the completed Phase 1 study and is expected to provide confirmatory data to support a Marketing Authorisation Application by demonstrating with statistical certainty that SPVX02 a room-temperature-stabilized Td vaccine has a similar to the immune performance to the globally-marketed Tetadif vaccine that also protects against tetanus and diphtheria.
Following the completion of the Phase 2b clinical trial, Stablepharma will continue engagement with EU health authorities and governments in an effort to assist in the commercial deployment of vaccines that remain stable outside the cold chain. It is hoped that Stablepharma's StablevaX technology will also transform global immunisation strategies, particularly in low- and middle-income countries, by improving coverage, reducing waste, and increasing vaccine access.
