AI-designed ‘universal vaccine’ candidate passes first human trial

An innovative universal vaccine technology has successfully completed its first human clinical trial. The study shows that the computationally designed vaccine candidate is safe, well tolerated, and capable of triggering immune responses against multiple coronaviruses

Human clinical trials

The open-label Phase 1 dose-escalation trial evaluated the vaccine candidate pEVAC-PS. The study involved 39 healthy volunteers between 18 and 50 years old who had previously received two or three doses of existing COVID-19 vaccines.

The trial took place at National Institute for Health and Care Research (NIHR) Clinical Research Facilities in Southampton and Cambridge. It was sponsored by the University Hospital Southampton NHS Foundation Trust, with primary funding from Innovate UK.

Participants were sequentially enrolled across four dose-escalation cohorts, receiving 0.2 mg, 0.4 mg, 0.8 mg, or 1.2 mg of the vaccine at day zero and day 28. The primary outcomes focused on safety and reactogenicity.

The results, published in the Journal of Infection, showed no significant safety concerns or serious adverse events, confirming the vaccine is safe for human testing.

How the super-antigen works

The pEVAC-PS vaccine was developed by the University of Cambridge and its spin-out company, DIOSynVax Ltd. Traditional vaccines use antigens from specific, pre-existing virus strains, meaning they must be updated frequently to keep up with mutations.

To create a future-proofed alternative, the research team used machine learning to analyse global genetic sequence data from the Sarbeco coronavirus group. The computer simulations identified common structural features shared across this entire virus family.

The team then designed a synthetic super-antigen containing these shared traits, allowing the vaccine to target current variants alongside related viruses that have not yet emerged in humans.

Needle-free jet delivery

The vaccine was administered as a DNA vaccine using a microfluidic jet injection device, specifically the PharmaJet Tropis Device. This needle-free delivery system uses a high-velocity, micro-fluid jet to deliver the vaccine intradermally through the skin.

This administration method provides an alternative for individuals with a fear of needle-based injections. It also has the potential to make large-scale vaccination campaigns faster and easier to complete, particularly in resource-limited settings where traditional needle-and-syringe delivery presents logistical challenges.

Study findings and next steps

The study evaluated immunogenicity by looking at antibody responses at day 56. Interpreting these results was complex because participants already possessed high baseline immunity and experienced varying exposure histories due to ongoing waves of Omicron variants during the trial.

Despite this pre-existing immune bias, participants developed measurable immune responses to the conserved features encoded in the vaccine, verifying that the computer-designed antigen strategy functions as intended.

Before the human trials, pre-clinical animal testing had already demonstrated that the vaccine candidate generated strong immune responses across a range of coronaviruses. To progress toward public use, the researchers are planning a larger Phase 2 trial. This next phase will assess the vaccine’s ability to induce strong, broadly protective immune responses in a wider and more diverse population.