The first human clinical trial of a universal Sarbeco coronavirus vaccine, developed by the University of Cambridge and spin-out DIOSynVax (DVX) Ltd, has shown that the vaccine is safe and has no significant side-effects.
The trial, involving 39 healthy volunteers, tested a vaccine designed to provide protection against multiple Sarbeco coronaviruses - the large group of viruses that occur in nature including SARS-CoV-2, which caused the COVID pandemic.
The vaccine triggered immune responses in the volunteers not only to SARS-CoV-2 and SARS, but to related bat viruses that could potentially jump from animals to humans and cause future pandemics.
This trial proves the safety of an entirely new way of designing vaccines. The technology uses an AI-designed 'super-antigen' to provide lasting protection against a broad range of viruses - for example the Ebola group, or Sarbeco coronavirus group - even as they mutate.
Vaccines developed in this way could protect against future emerging virus threats. The technology also reduces the need for frequent reformulation, which is a fundamental limitation of current vaccines.
This is the first time that a vaccine whose active component was designed entirely by computer simulations has been tested in humans.
Participants took part in the trials at National Institute for Health and Care Research (NIHR) Clinical Research Facilities in Southampton and Cambridge. The study was sponsored by University Hospital Southampton NHS Foundation Trust (UHSFT).
The results are published in the Journal of Infection .
"We've converted vaccine development from being reactive to being future proof. Our vaccines will continue to provide protection against viruses even as they mutate into new strains," said Professor Jonathan Heeney from the Lab of Viral Zoonotics, University of Cambridge's Department of Veterinary Medicine, the scientific lead of the research.
He added: "We've overcome the problem of traditional vaccines, which have limited protection. It means we can escape the constant cycle of chasing the virus variants circulating in humans and updating the vaccines to try to catch up, like a dog chasing its tail."
The antigen is the active ingredient in a vaccine – it triggers the body's immune system to produce a protective immune response, training it to fight off future infection by a broad array of pathogens containing these specific DVX antigens.
Current vaccines, such as the seasonal flu vaccine and existing Covid-19 vaccines, use antigens from specific virus strains or variants that have already been detected in humans. But since viruses are constantly mutating, by the time these traditional vaccines are manufactured and distributed, they have limited protection and must be updated annually in an effort to keep up.
To design the antigen for a universal coronavirus vaccine, the team used all the available genetic sequence data for Sarbeco coronaviruses logged by surveillance programmes around the world. Using machine learning, they then designed a super antigen containing the antigen features common to this whole group of viruses – including ones that haven't emerged yet.
Human clinical trials
The vaccine was given to volunteers between 18 and 50 years old at the NIHR Southampton Clinical Research Facility at UHSFT, and at the NIHR Cambridge Clinical research Facility at Addenbrookes Hospital, Cambridge.
The super antigen is compatible with most vaccine delivery systems. In this trial it was administered as DNA vaccine through a micro fluid jet. This needle-free delivery method offers an alternative to those with a fear of needle-based injections. This could make vaccination faster and easier to carry out in large numbers of people, especially in settings where conventional injections are more challenging to deliver.
A previous trial in animals - an important step before beginning human clinical trials - found that the vaccine provided a strong immune response against a range of coronaviruses.
Further development of the vaccine is needed before it is ready for public use. A larger Phase 2 trial will next assess the vaccine's ability to induce immune responses in a wider and more diverse population, and confirm that it generates strong, broadly protective immune responses.
The continuous pandemic threat
"Viruses like Influenza, Coronaviruses and the Ebola group are evolving continuously and by the time vaccines are rolled out, they may be poorly matched - the current "reactive" vaccine system struggles to keep pace," said Professor Saul Faust from the University of Southampton, the trial's chief investigator.
He added: "This new class of universal vaccines are future-proofed. They not only protect against many variants simultaneously, but potentially against related viruses that haven't yet emerged and spilt over to humans.
"If we can develop and clinically advance this new class of vaccines before a virus outbreak begins, millions of lives could be saved, lockdowns avoided and the economy preserved."
Professor Marian Knight, Scientific Director for NIHR Infrastructure, said: "The remarkable success of this AI-designed 'super-antigen' trial marks a pivotal leap forward in our ability to deliver broad, lasting viral protection."
She added: "This milestone was only made possible through partnerships between the life sciences sector and our world-class NIHR infrastructure in Cambridge and Southampton, whose Clinical Research Facilities provided the vital expertise and environment needed to safely fast-track this innovation, and bring it one big step closer to patients."
Coronaviruses such as SARS-CoV-2 and related Sarbeco coronaviruses continue to pose a threat to public health. A wide range of these and other viruses continue to circulate in animals that could potentially jump to humans at any time – but it's not possible to predict which one, or when.
The research was primarily funded by Innovate UK. The DIOSynVax pipeline includes vaccine candidates for human seasonal Flu and the pandemic influenza threats, haemorrhagic fever viruses, and coronaviruses including SARS-CoV-2.
DIOSynVax - Digitally Immune Optimised Synthetic Vaccines - is a spin-out company from the University of Cambridge, established in 2017 with the support of Cambridge Enterprise, the University's commercialisation arm. Jonathan Heeney is the Professor of Comparative Pathology at the University of Cambridge, and a Fellow at Darwin College.
