The hardest part of delivering a vaccine is usually not making it. It is keeping it cold.
A dose leaving a European fill-finish plant has to stay between 2 and 8 degrees Celsius through a container ship, a customs warehouse, a regional cold store, a district hospital, a motorcycle pannier and a village clinic’s kerosene fridge. Every link needs power, monitoring, and someone to notice when the temperature drifts. The refrigeration equipment, the vehicles, the technicians and the diesel routinely account for a large share of what an immunisation programme costs, and the failures are invisible: a vial that spent an afternoon at 35 degrees looks exactly like a vial that did not. It gets injected anyway.
That constraint shapes which vaccines reach which people. So a result published on 5 August in eClinicalMedicine is worth reading carefully, and worth reading with the limitations attached.
What was tested
Stablepharma, a UK company, took an existing tetanus-diphtheria booster and reformulated it so that the active components survive without refrigeration. The reformulated product, SPVX02, held its potency for at least 24 months at temperatures up to 30 degrees Celsius, and retained potency after three cycles of deliberate abuse between minus 20 and plus 40 degrees.
The phase 1 trial ran at three UK sites, led by Saul Faust at the University of Southampton, with the NIHR Clinical Research Facility at University Hospital Southampton and the Medicines Evaluation Unit in Manchester. Sixty healthy adults aged 18 to 55, all of whom had last received a tetanus-diphtheria shot at least a decade earlier, were randomised one-to-one-to-one into three groups of 20. One group received SPVX02. The other two received Tetadif and diTeBooster, both licensed and in routine use.
The design choice worth noting is the comparator. This trial did not test the new vaccine against a placebo, which would have been easier and less informative. It tested it against the two products it would have to replace.
The numbers
The primary endpoint was safety, not efficacy. Fifty-four of the sixty participants reported adverse events across all three arms, all mild to moderate — the sore arms and transient malaise that follow most injections. There were no grade 3 or higher events, no serious adverse events, and no suspected unexpected serious adverse reactions in any group.
On immunogenicity, measured 28 days after the single dose: every participant in every arm reached the accepted seroprotection threshold for tetanus, defined as anti-tetanus antibody at 1.0 international units per millilitre or above. For diphtheria, at a threshold of 0.1 IU/ml, seroprotection was 100 per cent in the SPVX02 arm and the Tetadif arm, and 95 per cent — 19 of 20 — in the diTeBooster arm.
Read plainly, the thermostabilised vaccine did what the two licensed vaccines did, in a group of adults whose immune systems had already seen these antigens.
What this does not show
That last clause matters more than the headline.
These were booster doses in previously immunised adults. A booster in a primed immune system is the easiest immunological test there is; the memory response is already built and needs only to be woken up. Nothing here speaks to how SPVX02 would perform as a primary series in an unvaccinated infant, which is where tetanus and diphtheria vaccination actually does its work.
Twenty people per arm cannot detect an uncommon safety signal, and the trial was not powered for statistical comparison between groups. Linda Klavinskis of King’s College London noted that 28-day immunogenicity is not the same thing as durability: tetanus protection is supposed to last a decade, and this trial says nothing about year three. Hamid Merchant at the University of East London flagged the cohort’s composition — roughly 95 per cent white, all between 18 and 55 — and that the freeze-thaw robustness rests on laboratory stability studies rather than clinical evaluation of frozen-then-thawed doses in people.
The sharpest caveat comes from Tuck Seng Wong at the University of Sheffield, who directs the UK-Southeast Asia Vaccine Manufacturing Research Hub: much of the low- and middle-income world runs well above 30 degrees Celsius, with large daily swings. Stability to 30 degrees is a genuine advance over 8 degrees. It is not the same as stability anywhere.
There is also a claim circulating alongside this result that deserves handling with tongs. The figure that half of all vaccines worldwide are wasted traces to a 2005 WHO paper and is still repeated, including by UNEP. It bundles closed-vial wastage from cold-chain failure together with open-vial wastage — the unused doses left in a ten-dose vial when only four children turn up — which is expected, planned for, and not a refrigeration problem. Country-level figures are frequently in the single digits to low teens. Removing the cold chain would eliminate a real category of loss. It would not halve global vaccine waste.
Why the platform matters more than the product
Tetanus-diphtheria boosters are not where the unmet need is greatest. They are cheap, off-patent, and widely available. What makes this interesting is that Stablepharma’s approach, which it calls StablevaX, is a reformulation applied to an already-licensed vaccine rather than a new vaccine built from scratch.
That is a regulatory shortcut with real value. A reformulated version of a known product carries a much lighter evidentiary burden than a novel antigen, because the immunology is already established and the question narrows to whether the reformulation preserves it. If the platform generalises, the same route could be run on vaccines where the cold chain bites harder — the company has named hepatitis B and HPV as candidates, both of which reach populations that are difficult to serve precisely because of delivery logistics.
The evidence that it generalises does not yet exist. One antigen pair, in one product, in sixty people, is a single data point about a platform.
A phase 2b trial with a larger cohort was approved in June 2026 and is under way. The company expects to complete clinical development in 2027, which on any realistic reading of regulatory timelines puts licensure somewhere beyond that. The work was supported by Innovate UK, with specialist testing from the UK Health Security Agency.
The R&D takeaway
The interesting target here is not the vaccine, it is the constraint. Cold chain is an infrastructure tax levied on every biologic that has to travel, and reformulation attacks it at a fraction of the cost of building more refrigeration. For funders, the leverage sits in platform validation across multiple antigens rather than in any single product — and the next question worth paying for is whether thermostability holds in a primary series and at temperatures above 30 degrees, since that is where the deployment case actually lives. Treat a phase 1 with sixty participants as evidence that the approach is worth funding further, not as evidence that it works.
Sources
- 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, eClinicalMedicine, 5 August 2026
- Preprint version of the trial report, medRxiv
- Expert reaction to phase 1 trial of SPVX02, Science Media Centre
- Fridge-free vaccine shows promise of reaching millions worldwide, University of Southampton
- Monitoring vaccine wastage at country level, World Health Organization
The R&D Innovate desk