All around Oxford, thousands of people have been mobilised in the fight against COVID-19. The city is home to scores of pioneering academic and medical institutions and hundreds of innovative research facilities. This unique life sciences cluster has pivoted rapidly and its experts are now battling the virus on many fronts, with vaccines, new drug treatments and diagnostics.
“There is a phenomenal infrastructure here for the delivery and development of tools to fight disease,” said Professor Helen McShane, director of the Oxford NIHR Biomedical Research Centre and deputy head of the University of Oxford’s Medical Sciences Division. “Oxford has a long-standing interest in all aspects of infectious diseases, including modelling and vaccines. There is an increasing recent focus on emerging pathogens. The breadth of science in this area spans vaccine and drug development, experimental medicine clinical trials, large Phase III trials and diagnostics.”
Vaccines
Helen is a professor of vaccinology at the University’s Jenner Institute, one of the world’s largest research institutions dedicated to non-profit vaccine research.
The Jenner Institute has developed the UK’s primary vaccine candidate, ChAdOx1 nCoV 19, in record time, moving from design to human clinical trials in just four months. The Jenner’s rapid response was led by Professors Adrian Hill and Sarah Gilbert, who acted as soon as the first six virus sequences were published in early January. By April 30, the Institute had forged a not-for-profit partnership with AstraZeneca so that, if the vaccine proves successful, its manufacture and distribution can be rapidly scaled up. Around 700 people had been vaccinated by early May and the first results could be seen by Autumn.
Meanwhile, the arrival of the pandemic has accelerated the construction of the UK’s first bespoke strategic vaccine development and manufacturing capability, the £67 million Vaccines Manufacturing and Innovation Centre (VMIC) at the Harwell Science and Innovation Campus south of Oxford. Originally scheduled for the Spring of 2022, the centre is now due to open its doors next year. The 7,000m2 building will be a key pillar of the Harwell HealthTec Cluster, where 58 organisations collectively employ 1,250 people, and it is part of a new Life Science Opportunity Zone at Harwell where 6,000 people work. VMIC will be co-located with the UK’s open access National Laboratories, including The Rosalind Franklin Institute and the Diamond Light Source.
The Diamond Light Source is the UK’s national synchrotron, accelerating electrons to near light speeds to give off light ten billion times brighter than the sun. These beamlines can be directed to help study a vast range of subject matter through a machine that is 10,000 times more powerful than a traditional microscope. This potency, and the efforts of Diamond’s director of life sciences and structural biologist Professor David Stuart and many others around the world, has now been harnessed to the global effort to help advance work on SARS-CoV-2, probing small chemical ‘fragments’ of the protease as potential drug target binding sites. SARS-CoV-2 potentially has many proteins that can be used as drug targets and this facility’s speed and scale has been vital.
Diamond is a key participant in the global COVID Moonshot effort, which has brought together international scientists from academia and industry in a non-profit initiative, in conjunction with machine learning-powered medicinal chemistry company PostEra. Moonshot aims to develop a clinically effective antiviral at the fastest rate ever seen by using crowdsourcing techniques to call on chemists around the world to design new inhibitors using the rich fragment data that Diamond has managed to capture.
All data is being made available to the world’s scientific community and promising compounds will be synthesised and tested. The ambition is to have several potential antivirals in a few months, giving some options before a vaccine is ready for wide use. Other local partners include Protein Production UK, based at The Rosalind Franklin Institute, which is developing reagents to stabilise selected SARS-CoV-2 proteins, and pharmatech company Exscientia, working with Scripps Research to screen over 15,000 clinical drug molecules using AI and biosensors.
“One of the positive things to come out of this pandemic is the team science,” noted Helen McShane. “Groups have coalesced very quickly to work together collaboratively on the vaccine and diagnostics development, both in Oxford and the surrounding area. Companies are putting aside commercial differences and working together. Here, with the concentration of spin-outs and new companies, it’s about synergy and the things that the university and industrial partners can do together.”
She and her Oxford team are working with Birmingham’s Biomedical Centre on one of four new platform trials being fast- tracked around the country, to test treatments for the disease, each assessing the effects of a range of drugs on around 60-100 subjects. Those showing promise will be fed into larger-scale COVID-19 studies.
Treatment trials
As the urgent search for treatment continues, two big trials have originated in Oxford. RECOVERY, the world’s largest randomised clinical trial of potential coronavirus treatments, is well underway, with over 9,000 participants recruited from 160 hospitals. It has tested a range of established treatments including those used to treat HIV (lopinavir-ritonavir), inflammation (low-dose dexamethasone), malaria (hydroxychloroquine) as well as antibiotic azithromycin and injected anti-inflammatory tocilizumab. Read-outs are expected in a few weeks.
PRINCIPLE, the first clinical trial in COVID-19 patients consulting in primary care, will initially test if hydroxychloroquine can reduce the need for people to go to hospital or speed up their recovery, helping to ease the burden on hospitals.
Another team is analysing concomitant medications and whether some make people more or less susceptible. Further multidisciplinary work into the mental health impacts of COVID-19, both for those in hospital settings as well as at home, will seek to find predictors and support for those who are suffering.
Outside the University, Oxfordshire companies participating in therapy trials include Perspective Diagnostics, which has started a trial of chloroquine or hydroxychloroquine with azithromycin, with promising results in China and France, and BerGenBio, a clinical-stage oncology biopharma company based at the Oxford Science Park.
Its once-a-day oral drug bemcentinib is the first to be fast-tracked as a potential treatment through the government’s ACCORD trial initiative. Izana Bioscience is trialling namilumab, its Phase III ready fully monoclonal antibody therapy for patients with rapidly- worsening health.
Immunology
“There are not many angles that we are not actively pursuing,” says Professor Gavin Screaton, head of the University’s Medical Sciences Division. A number of research teams are studying the body’s response to SARS-CoV-2 infection, working closely with local hospital trust clinicians who can provide samples from COVID-19 patients. Professor Screaton’s focus is on developing monoclonal antibodies, building on his experience at Imperial College London in targeting the Zika virus. These involve finding out which antibody- producing cells from an infected individual are making antibodies and then making them artificially, perhaps combining two or three, before they are put back into people. Technology has advanced techniques which would normally take a year, to six months, and trials – whether from Oxford or another centre – are likely to begin in the next few months.
Testing
Oxford has been very active in testing and again was able to act early. One of centres chosen to develop polymerise chain reaction (PCR) swab testing on people who are actively infected with COVID-19 was the UK Biocentre in Milton Keynes, which is run by the university. PCR tests detect the presence of an antigen, rather than the presence of the body’s immune response, or antibodies, and can tell whether or not someone has the virus. Here again the Oxfordshire ecosystem kicked in when Oxford Nanopore, a company that normally works on DNA sequencing, was able to provide some of the chemical reagents needed to carry out the tests after the government warned of a potential shortage.
Oxford Nanopore’s sequencing technology is being used globally to support genomic epidemiology and it is participating in a genome sequencing alliance to enable rapid analysis of patients testing positive for COVID-19.
The Native Antigen Company, another Oxfordshire company, has used its expertise in antigen development combined with local company Oxgene’s proprietary Adenovirus Protein Machine technology to accelerate the production of SARS-CoV2 reagents. Meanwhile, Absolute Antibody is providing antibody engineering, manufacturing services and coronavirus-related reagents.
Understanding the prevalence of the infection could be key to getting the world back to work and Sarah Walker, the University of Oxford’s professor of medical statistics and epidemiology, is leading a national serological survey, working with a data science company to help understand this in the UK. It will involve 25,000 participants initially, ramping up to 300,000 over the next 12 months, who will provide nose swabs and blood samples.
Of course, work is concurrently going on around the world in many academic, pharmaceutical and life sciences institutions. As Prof Screaton observes: “We hope there will be many more than one winner,” but there is no doubt of Oxfordshire’s wide-ranging contribution, as summed up by Chas Bountra, Oxford University’s Pro Vice-Chancellor for Innovation: “While pandemics shouldn’t be a surprise, the timing always is. The response from Oxfordshire’s life sciences community was immediate and comprehensive. Notwithstanding many challenges, including the need for social distancing, thousands of world-leading researchers and clinicians, from a range of disciplines, have been working together seamlessly to great effect. It’s a remarkable ecosystem which is proving itself capable of answering some of the biggest questions facing populations globally.”
Sebastian Johnson is head of innovation and inward investment for the Oxfordshire Local Enterprise Partnership (OxLEP)
