University of Bristol: Collaborative COVID-19 lockdown effort delivers major boost for vaccine innovation in Bristol

ADDomer is a new type of vaccine that can be produced and stored at warmer temperatures, removing the need for refrigeration, in a major advance in vaccine technology. For comparison, COVID-19 vaccines by AstraZeneca, Moderna and BioNTech need to be cooled at 4°, -20° or even -80°. ADDomer, engineered using a synthetic thermostable protein scaffold, could revolutionise the way vaccines are designed, produced and administered.

Early in 2020, the COVID-19 pandemic began to circulate around the globe, entailing major disruption to communities and economies. In March 2020, the UK went into its first lockdown and Bristol turned into a ghost town. University research was put on hold, laboratories closed and people stayed at home amidst uncertainty.

This was when Frederic Garzoni, CEO of Imophoron Ltd, reprised his old role, to produce high-value protein reagents for scientists who carried on trying to tackle the global health crisis. Working with Bristol scientists, Fred developed within weeks a COVID-19 vaccine utilising Imophoron’s innovative ADDomer vaccine technology.

Professor Adam Finn, Director of Pfizer’s new Vaccine Centre of Excellence in Bristol, recalled: “These were momentous times. Worrisome, no doubt, but scientifically extremely motivating. We had a new, deadly pathogen, SARS-CoV-2, sweeping the globe. Scientists everywhere mounted an unprecedented effort to decipher SARS-CoV-2 and the disease, in record time.”

In Bristol, led by Professor Finn, the University COVID-19 Emergency Research group, Bristol UNCOVER, emerged, comprising clinicians, virologists, chemists, biologists and other academics. Professor Finn explained: “In the clinic, we needed fragments of SARS-CoV-2, so-called antigens, to develop tests to detect antibodies in the blood of people who had contracted the virus.”

Imre Berger, Director of Bristol’s Max Planck Centre for Minimal Biology, said: “When Adam called, my core team members immediately volunteered for this task. We joined Bristol UNCOVER and produced what our colleagues needed in our protein expression facility. Fred had been our facility manager before we founded Imophoron Ltd. We needed him back now, and he came.”

Fred Garzoni added: “There was no question that Imophoron joined the effort of Bristol UNCOVER. I had worked with Imre for many years, managing the facility when we were still in France. We had discovered a thermostable scaffold, the ADDomer. The ADDomer is uniquely suited as a vaccine platform to combat infectious diseases. I came to Bristol in 2017, enabled by a Talent and Mobility award from BrisSynBio, the University’s UKRI-funded Synthetic Biology Research Centre, and set up Imophoron in the UK to produce thermostable vaccines to combat tropical infectious diseases such as Chikungunya.”

Working at the University with Bristol UNCOVER provided a unique opportunity not only to supply Bristol UNCOVER scientists with the reagents they required, but also to test the ADDomer technology and develop, as fast as possible, an effective COVID-19 vaccine, different from any other vaccine developed and deployed to date.

“We had access to everything and everybody we needed through Bristol UNCOVER” said Fred Garzoni. “Colleagues including Mick Bailey, Jamie Mann, Joe Roe, David Morgan and their incredibly hard-working teams at the Vet School and the ASU were thrilled to help develop a completely novel type of COVID-19 vaccine.” Together, the scientists put the ADDomer vaccine candidate, designed by Fred, to work.

Before using animal models, the design was validated by cryo-electron microscopy (Cryo-EM), a powerful imaging technique brought to Bristol by Christiane Schaffitzel, Professor of Biochemistry and also part of Bristol UNCOVER.

“Cryo-EM depicts particles at near atomic resolution” explained Professor Schaffitzel. “Seeing Fred’s vaccine design in such detail gave us confidence that we were on the right track.”

Critically, this imaging technique depends on powerful computation. As the pandemic unfolded, Oracle, a key collaborator in the ADDomer vaccine development programe, provided access to their high-performance cloud infrastructure. The Cryo-EM work, accelerated by Oracle Cloud, was instrumental to move the COVID-19 vaccine design forward rapidly to real life-trials in animal models at the pace required in a pandemic.

Fast forward to today. The work carried out during lockdown highlighted Imophoron’s ability, even under adverse conditions, to rapidly generate vaccine candidates with the ADDomer platform within weeks, suitable for pandemics such as COVID-19. In preclinical models, the ADDomer COVID-19 vaccine, induced strong immune responses, with the potential to prevent disease progression, but critically, also to interrupt transmission.

The Bristol UNCOVER work revealed that the ADDomer COVID-19 vaccine can be delivered by various administration routes, including intranasal, which would end the need for trained healthcare professionals to administer the vaccine, reducing the cost and complexity of rolling out a pandemic vaccine programme.

Effective and simple manufacturing, and thermostability sets this vaccine platform apart from others including mRNA based vaccines, which has become one of today’s leading type of vaccines. Imophoron’s vaccine candidates would allow global distribution with no cold chain needed, worldwide. Today’s Imophoron funding announcement to advance ADDomer vaccines to the clinic, is a major boost for vaccine innovation in Bristol and beyond.

“I realise how difficult the lockdowns have been for everyone,” said Fred Garzoni. “Many people have lost loved ones, had mental health issues and are still recovering. For us, however, it was probably the most captivating time in our lives as scientists, and for Imophoron it made the difference. The sense of purpose, the incentive, the focus, and the shared success. I can only thank everybody involved for that.”