Fridge-free tetanus-diphtheria vaccine matches licensed shots in first human trial

A tetanus-diphtheria shot that sat for two years at 30°C has cleared its first human trial, matching two licensed refrigerated boosters on safety and antibody levels.

Sixty healthy adults at Southampton’s NIHR Clinical Research Facility received either SPVX02, the room-temperature formulation, or one of two approved vaccines, Tetadif or diTeBooster. Twenty people stood in each arm. Recruitment ran from 1 April to 22 September 2025. At day 28, every person who got SPVX02 had protective antitoxin levels against both tetanus and diphtheria. No vaccine-related serious adverse event appeared in any group. Sore arms were mild to moderate and evenly spread.

The paper sits in eClinicalMedicine, a Lancet journal. Saul Faust, the principal investigator, said the trial showed proof of concept in humans and equivalent immune responses. For anti-tetanus titres, SPVX02’s day-28 geometric mean was 12.03 IU/mL, close to diTeBooster at 13.94 and above Tetadif at 5.37. People who started below 0.1 IU/mL boosted at similar rates across the three arms.

SPVX02 is Tetadif dried with trehalose, the sugar that lets the desert resurrection plant revive after drought, then stored as powder and mixed with water before injection. Stablepharma, a UK firm backed by UK Research and Innovation, ran a parallel stability programme at NetpharmaLab in Spain. Vials held potency after 24 months at 30°C and 75 percent humidity, after six months at 40°C, and after three freeze-thaw cycles.

The World Health Organization has estimated that about half of all vaccine doses are wasted because the cold chain breaks. Tetanus and diphtheria remain killers in places where a fridge truck does not run. A powder that survives 30°C for two years changes the logistics more than it changes the immunology. The antigens are known. The packing is new.

Stablepharma has opened a Phase IIb study of 160 people to show non-inferiority against the licensed shot. Because the underlying vaccine is already approved, that trial could be the last large clinical step. Faust’s group says the formulation can handle a range from −20°C to 40°C.

Room-temperature vaccines have been promised before and have stalled in scale-up or with regulators who want more than 60 adults. This result is still a 60-person first-in-human study in Hampshire, not a rollout in a district without electricity. What it does prove is that the trehalose process left the antigens intact enough to look like Tetadif in blood tests.

If IIb copies Phase I, procurement agencies will have to decide whether a powder that skips diesel for the fridge is worth a new SKU, new training and a new leaflet. That decision, not the p-values from Southampton, will decide whether the resurrection-plant sugar ever leaves the trial freezer.

Tetanus kills through wounds that never see a clinic. Diphtheria returns when booster coverage drops. Both are problems of distance and electricity as much as of science. A vial that can ride in a dry box at 30°C for two years is a logistics product wearing a medical label. Regulators will still want the 160-person trial and manufacturing batches that look like the Southampton lots.

Procurement agencies waste money every year on ice packs and on doses that cooked in a stalled van. Those agencies will read the stability tables before they read Faust’s quotes. The tables say 30°C for 24 months and 40°C for six. That is the sentence that matters in a warehouse in March.

For now the facts are small and clear. Sixty adults. Three arms. Day-28 protection in all 20 who received the powder. Two years at 30°C on the shelf data. A larger trial already recruiting. The cold chain is still how most of the world moves tetanus shots. SPVX02 is the first time a reformulated Td vaccine has shown, in people, that it might not have to.