Oxford's Subtle Advantage in Britain's Vaccine Race


Illustration by Faridah Faiz

In the race to produce Britain’s first vaccine against COVID-19, there was only one clear winner from the start: Oxford.

It all seemed to be fair game in the early days of the pandemic. China shared the genetic sequence of the virus on 11 January 2020 and research groups worldwide went straight to work. By March 2020, the World Health Organization had named 41 research groups and pharmaceutical companies that were actively working on the vaccine [1]. Teams from Oxford, Cambridge, and Imperial College London were among them. Britain’s main contenders come as no surprise to those familiar with the life sciences dominance of the ‘Golden Triangle’, dubbed as such because of the high density of knowledge clusters in Oxford, Cambridge and London [2].


What is surprising is how things have unfolded since then. We all know the story with Oxford and AstraZeneca, but what happened to Cambridge and Imperial?

Trial run


The exact timeline of the Oxford-AstraZeneca COVID-19 trials is complicated (WIRED's Hilda Bastian kept tabs of all the announcements here), so the summary below is a necessary oversimplification.

Crude timeline of major clinical trial developments

Using progress through clinical trials as a benchmark, Oxford were able to test their vaccine in healthy volunteers (the first major milestone) within three months of learning the genetic code of the virus. Imperial reached that stage within five months, in June 2020 [3].


Cambridge only announced that they had secured funding for human trials in August 2020 [4] but had not actually commenced with the trials that year. Imperial's early-stage human trials were still ongoing by the time the Oxford-AstraZeneca vaccine was approved in December 2020, which has since led them to reassess their overall vaccine strategy.


This is an unfair way to compare three universities, of course. For one, Imperial developed their vaccine candidate in two weeks [5], i.e. just as fast as Oxford did. Cambridge have not made their development timeline public but it is likely that they had a candidate within the same period [6].


The teams have also taken novel approaches to training the immune system to fight the virus. It would be fairer to compare apples to Ferraris. DNA vaccines in particular, the focus of Cambridge's approach, are still in virgin territory; no DNA vaccines have been approved for human use to date, which probably explains Cambridge's longer path to human trials.


Comparison of the science behind the different vaccine types

Still, it is impressive that Oxford were as fast as they were. Previously on The Business of Science, we discussed the 'Valley of Death' in translational research and how funding drives the scientific agenda. How did they get around this? Oxford are certainly not immune to funding constraints.


Also, putting on my Cambridge wife hat for a second, understanding how they did it is important because no one here really wants to 'lose' to Oxford. If anything, this whole vaccine race has unearthed an innovation conundrum.


I think about this every time I walk past the old Cavendish Laboratory in Cambridge, the crucible of modern science. The place where James Watson and Francis Crick deduced the structure of the DNA double helix in 1953, thanks to the experiments of Rosalind Franklin. This kickstarted the chain of events that eventually led us to having DNA- and RNA-based vaccines today.

Nerding out at the old Cavendish Lab

Fast forward to 2020 and it is clear that excellence in basic research no longer confers a sustainable competitive advantage to any institution, let alone Cambridge. So what is going on?

One critical advantage


The story of how Oxford developed their vaccine in record time has been covered by numerous publications, including Oxford themselves. The team were fortunately already trialing their vaccine for MERS, another coronavirus, when the COVID-19 outbreak happened [7].


However, one aspect of their story really stood out from a business strategy standpoint: outsourcing. Or rather, a lack thereof in the initial stages.


Imagine that you and a friend are taking part in an engineering competition. To win, you need to be the first person to 3D print and deliver an object to solve Challenge X. You and your friend are matched in terms of skill and experience. You both have the software needed to build your respective digital models. Time to print.


Unfortunately for you, your friend happens to have a 3D printer at home. He only needs to walk across the room to get started. Meanwhile, you start making phone calls to either borrow someone's 3D printer or hire a third party to print it for you. All of this takes up valuable time that you could have spent inspecting and testing your printed product instead. Substitute the 3D printer for a biomanufacturing facility, and you have Oxford's critical advantage over the other research groups.


It was a subtle advantage. The Oxford team still had the difficult task of securing funding for larger clinical trials in the early days of the pandemic, just as the other groups did, but it was clear that having the facility onsite was a smart move. They still had to partner with a contract development and manufacturing organisation (CDMO) in Italy to make enough samples for larger trials, but this was their equivalent of having a 3D printer at home.


The Oxford vaccine research, manufacturing and clinical trials teams were a short walk away from each other

It was smart because the hardest part of getting your research out of the lab and into the world is convincing investors and pharmaceutical companies that your product was worth investing in. The ability to create trial vaccines using academic grant funding first affords Oxford the freedom to pursue high risk projects, like a vaccine that may or may not work.


This way, they can approach funders with a portfolio of data that shows how the vaccine performed in animal models and in a small group of healthy human participants [8] - a win for both researchers and funders. Not needing to outsource the manufacturing effectively lets Oxford perform their own Phase 1 trials quickly. By contrast, Imperial opted to partner with TriLink BioTechnologies, a CDMO based in California, for their Phase 1 trials [9].

Standing on the shoulders of Giants


On the surface, this seems like an Oxford success story. The deeper down the rabbit hole I went, the more I realised that this was not a case of The Best versus The Rest. If anything, this was the byproduct of years of smart science funding policies.


  1. Less about competition, more about collaboration: While we might say Oxford came out on top, Oxford's clinical biomanufacturing capabilities ultimately had its roots from developments in Cambridge. The facility was originally founded by two Cambridge University researchers funded by Britain's Medical Research Council (MRC) in 1990 [10]. The MRC then funded the move of the site to Oxford in 1995. Dr. Catherine Green, who heads the biomanufacturing site today, was trained in Cambridge [8]. Imperial are part of a network of universities pioneering the work at The Future Vaccine Manufacturing Research Hub, which are publicly-funded hubs set up to develop faster methods of manufacturing vaccines and to optimise current manufacturing methods [11]. Their research findings will ultimately benefit other researchers worldwide.

  2. Foresight and good funding policies: Sir John Bell, widely attributed as a key enabler of the Oxford vaccine initiative, was quick to remind the public that pandemics are the norm, not the exception. "I keep telling people these pandemics are not as rare as you think - people forget polio. Polio was a terrible, bloody disease."[12] Just like the old parable that there will be seven years of plenty and seven years of famine, pandemic preparedness serves to build an arsenal for when a crisis strikes. We have the Coalition for Epidemic Preparedness Innovations (CEPI), a partnership between public and private funders, to thank for their efforts to develop and deploy new vaccines to prevent future epidemics. CEPI and the UK government funded the trials for Oxford's MERS vaccine, which eventually acted as a template for Oxford's COVID-19 vaccine. Prior to the pandemic, CEPI funded the development of technologies to speed up vaccine manufacturing, so the world can respond quickly to 'Disease X' [13].

These are just a handful of the smart investment decisions made in the past that eventually led us to having multiple COVID-19 vaccines within a year of the outbreak. This pace of vaccine innovation was almost unheard of until 2020.


If we have seen further in this pandemic, it is only possible because we are standing on the shoulders of Giants [14]. Oxford's success is everyone's success.

References

  1. The race for a COVID-19 vaccine. Éanna Kelly. Science | Business.

  2. Knowledge Networks: London and the Ox-Cam Arc. New London Architecture.

  3. First volunteers receive Imperial COVID-19 vaccine. Imperial College London.

  4. Cambridge-developed SARS-CoV-2 vaccine receives £1.9million from UK government for clinical trial. University of Cambridge.

  5. In pictures: the Imperial lab developing a COVID-19 vaccine. Imperial College London.

  6. Coronavirus vaccine being created by Cambridge laboratory may offer best hope in tackling epidemic. Cambridge Independent.

  7. New MERS vaccine clinical trial starts in Saudi Arabia. University of Oxford.

  8. The Oxford Covid-19 Vaccine Production - A Year in the Fast Lane (webinar). Ingenieurs et Scientifique de France.

  9. TriLink BioTechnologies and Imperial College London Announce Collaboration to Produce saRNA for Covid-19 Vaccine Development. TriLink BioTechnologies.

  10. Turning Monoclonal Antibodies into Adenoviral Vectors - An Academic Perspective. University of Oxford.

  11. Future Vaccine Manufacturing Research (FVMR) Hub. Imperial College London.

  12. The fixer. Mark Mardell. Tortoise.

  13. Priority diseases. CEPI.

  14. In a letter to Robert Hooke in 1675, Isaac Newton made his most famous statement: "If I have seen further it is by standing on the shoulders of Giants".

Further reading

Thanks to Musaddiq Adam Muhtar for inspiring this article ("Why isn't there a Cambridge vaccine?") .