Systemic risks: Cambridge in viral vaccine breakthrough

A vaccine antigen technology developed by the University of Cambridge and spin-out DIOSynVax in response to COVID is now hoped will provide wide-ranging protection against a host of emerging viruses.

The vaccine, originally developed in early 2020, provided protection against all known variants of SARS-CoV-2 – the virus that causes COVID-19 – as well as other major coronaviruses, including those that caused the first SARS epidemic in 2002.

The studies in mice, rabbits and guinea pigs – an important step before beginning human clinical trials, currently underway in Southampton and Cambridge – found that the vaccine candidate provided a strong immune response against a range of coronaviruses by targeting the parts of the virus that are required for replication. The vaccine candidate is based on a single digitally designed and immune-optimised antigen.

Even though the vaccine was designed before the emergence of the Alpha, Beta, Gamma, Delta and Omicron variants of SARS-CoV-2, it provided a strong protection against all of these and against more recent variants, suggesting that vaccines based on DIOSynVax antigens may also protect against future SARS-CoV-2 variants.

DIOSynVax (Digitally Immune Optimised Synthetic Vaccines) uses a combination of computational biology, protein structure, immune optimisation, and synthetic biology to maximise and widen the spectrum of protection that vaccines can provide against global threats including existing and future virus outbreaks. Its vaccine candidates can be deployed in a variety of vaccine delivery and manufacturing platforms. 

The results are reported in the journal Nature Biomedical Engineering.

Since the SARS outbreak in 2002, coronavirus ‘spillovers’ from animals to humans have been a threat to public health, and require vaccines that provide broad-based protection. “In nature, there are lots of these viruses just waiting for an accident to happen,” said Professor Jonathan Heeney from Cambridge’s Department of Veterinary Medicine, who led the research. “We wanted to come up with a vaccine that wouldn’t only protect against SARS-CoV-2, but all its relatives.”

All currently available vaccines, such as the seasonal flu vaccine and existing Covid-19 vaccines, are based on virus strains or variants that arose at some point in the past. “However, viruses are mutating and changing all the time,” said Heeney. 

“Current vaccines are based on a specific isolate or variant that occurred in the past, it’s possible that a new variant will have arisen by the time we get to the point that the vaccine is manufactured, tested and can be used by people.”

Heeney’s team has been developing a new approach to coronavirus vaccines, by targeting their ‘Achilles heel’. Instead of targeting just the spike proteins on the virus that change to evade our immune system, the Cambridge vaccine targets the critical regions of the virus that it needs to complete its virus life cycle. The team identifies these regions through computer simulations and selecting conserved structurally engineered antigens. “This approach allows us to have a vaccine with a broad effect that viruses will have trouble getting around,” said Heeney.

Based on a strong safety profile, the “first-in-human” clinical trials are ongoing at Southampton and Cambridge NIHR Clinical Research Facilities. The last booster immunisations will conclude by the end of September.

“Unlike current vaccines that use wild-type viruses or parts of viruses that have caused trouble in the past, this technology combines lessons learned from nature’s mistakes and aims to protect us from the future,” said Heeney. “These optimised synthetic antigens generate broad immune responses, targeted to the key sites of the virus that can’t change easily. It opens the door for vaccines against viruses that we don’t yet know about. This is an exceptionally different vaccine technology – it’s a real turning point.”