Professor Jonathan Heeney is a man in a hurry. The Cambridge virologist is working around the clock to develop a vaccine to beat the coronavirus Covid-19.
The professor, who is head of the Laboratory of Viral Zoonotics at the University of Cambridge, is hopeful that his vaccine candidate will be ready for human clinical trials as early as June.
His next step is to test the vaccine in pre-clinical trials, which means giving the vaccine to mice to check it is safe for human trials. As the physiology and immune systems of mice are similar enough to humans, researchers can reduce the risk to humans taking part in trials.
But Heeney needs more funding to take his work to the next stage, and a pharmaceuticals partner for clinical trials. In an interview published by the university on the Cambridge Research Bulletin, he said: “We need a ‘big pharma’ partner to help us scale up our activities. Our vaccine designs are made so that they can be easily integrated into any proprietary vaccine platform that a pharmaceutical company may have ready.”
The Canadian professor claims the technology developed by his company, DIOSynVax, has “changed the way vaccines are made” because of the computer modelling he uses.
He set up DIOSynVax three years ago as a spin-out from his work on new vaccines and is supported by Cambridge Enterprise, the university’s commercialisation arm. With significant funding from the Bill & Melinda Gates Foundation and Innovate UK, his work led to new vaccines being designed for diseases ranging from influenza to Ebola and other haemorrhagic fevers.
DIOSynVax is a small start-up so to scale up to make big quantities of vaccines for mass-scale vaccination would be impossible unless it were to partner up with a big pharma. “But if we could partner up very shortly with big pharma, we could move as fast as they could move.”
He is in regular contact with Public Health England, informing them of developments in his work. A normal vaccine process usually takes up to 12 years and costs £500million.
Heeney’s laboratory is one of around 41 research groups and pharma specialists known to be working around the world on developing a vaccine. So far only Moderna Inc, a biotech company based in Cambridge, Massachusetts, and funded by the US National Institutes of Health, has held the first human trial with an nRNA vaccine.
Others companies include Britain’s GSK, Johnson & Johnson, Inovio Pharmaceuticals and Novavax in the US, Germany’s CureVac and BioNTech, Israel’s Migal Galilee Research Institute and research teams at Oxford University, Imperial College, London and the University of Queensland.
Heeney has been working on finding a vaccine against Covid-19 since the Chinese released its genetic sequence on January 9, some 10 days after the first cases from Wuhan were reported by the Chinese to the World Health Organization.
Until now, coronaviruses have presented a particular challenge to vaccine developers although they are relatively common in veterinary medicine, says Heeney, who is also a vet. He describes the moment when these viruses cross into the human population as “like going to a poker game: You never know who is sitting at the table.”
He explains why they are so difficult to design: “Coronaviruses are named after their appearance as they are spherical objects, on the surface of which sit ‘spike’ proteins.”
“The virus uses these spikes to attach to and invade cells in our body. Once inside, the virus uses the cell’s own machinery to help itself replicate and spread throughout the body, causing disease and allowing it to transmit onwards.”
Traditionally, scientists developed vaccines that program the body to produce antibodies that recognise and block these spikes. “However, this strategy can misfire with coronaviruses due to a phenomenon known as ‘antibody-induced enhancement’ or ‘vaccine-induced enhancement’.”
He adds: “If you make antibodies against the spike, they can end up binding to it and helping the virus invade important immune cells known as monocyte-macrophages. Rather than destroying the virus, these cells can then end up being reprogrammed by the viruses, exacerbating the immune response and making the disease much, much worse than it would otherwise be.”
DIOSynVax’s approach is faster than other developers, he says, because it uses computer modelling of the virus’s molecular structure. “This is created using information on the COVID-19 virus itself as well as its relatives – SARS, MERS and other coronaviruses.”
“Then we can identify chinks in its armour, crucial pieces of the spikes that will form part of the vaccine, to disable the virus but without making the infection worse.”
As a vaccine strategy must be laser specific, targeting those domains of the virus’s structure are critical for docking with a cell, while avoiding the parts that could make things worse. Heeney’s technology does just that.
His ground-breaking approach looks at the genetics of the viruses. This allows his researchers to identify the key piece of genetic code which the virus uses to produce the essential part of its coat, ‘the spikes’, that are important for docking with a cell, and to target these elements with the vaccine.
This modelling creates a mirror image of the virus without its bad parts, the non-essential parts that could trigger those bad immune responses. “What remains is just the magic bullet, essentially, to trigger the right type of immune response.” Let’s hope Heeney and his Cambridge team get the backing and partner they need, and quickly. The world is praying for his magic bullet.
