The COVID vaccine makers tell all

Vaxxers: The Inside Story of the Oxford AstraZeneca Vaccine and the Race Against the Virus Sarah Gilbert & Catherine Green Hodder & Stoughton (2021)

The Vaccine Directors: Catherine Gale & Caleb Hellerman Wingspan (2021)

Last August, biologist Catherine Green was camping with her daughter in Wales when a chance conversation at the pizza van turned to a familiar topic: COVID-19. “We don’t know what they put in these vaccines,” a fellow camper told her. “I don’t trust them. They don’t tell us the truth.”

Green was uniquely placed to know. She runs a clinical biomanufacturing facility at the University of Oxford, UK, and is part of a team that had developed a COVID-19 vaccine that was in clinical trials at the time. Pharmaceutical company AstraZeneca of Cambridge, UK, aims to produce three billion doses of this vaccine for distribution around the world by the end of 2021, significantly protecting people from severe disease and death. Yet, nearly a year after Green’s encounter, conspiracy theories continue to stymie take-up of COVID-19 vaccines, risking lives both in regions where doses are abundant, and in those where there are precious few. In April, the non-profit Kaiser Family Foundation, based in San Francisco, California, found that 54% of US adults either believe common misinformation about COVID-19 vaccines or think that it might be true (see go.nature.com/3fyfaoi).

It was with the epidemic of misinformation in mind, Green says, that she and Oxford vaccinologist Sarah Gilbert decided to write Vaxxers, a behind-the-scenes story that attempts to humanize vaccine-making in the hope of boosting trust. The book, along with The Vaccine — a documentary commissioned by the BBC and CNN Films — offers a welcome glimpse inside the race to develop COVID-19 vaccines in the middle of a raging pandemic.

The book and documentary are a useful pairing. The film follows five research groups as they forgo sleep and family time to develop vaccines using approaches ranging from tried-and-true inactivated viruses to cutting-edge messenger RNA techniques. The book is a deep dive with one team as it juggles funding stress, press interviews and domestic responsibilities. All the groups painstakingly balance the need to be careful and methodical with the pressure to create and test a vaccine faster than ever before. They carry the hopes of the world — and they know it.

The film’s images reveal the toll of relentless stress. At the University of Queensland in Brisbane, Australia, virologist Keith Chappell’s eyes grow progressively redder and his clothing more dishevelled. The slump in his shoulders after he learns in December that his protein vaccine must be abandoned is heartbreaking. Wu Guizhen, a biosafety specialist at the Chinese Center for Disease Control and Prevention in Beijing, describes her coping mechanisms: “When it feels like you’re too tired to go forward,” she says, “my solution is to sleep for a bit while standing.”

The documentary occasionally slips into a prominent narrative of the time: the idea of a race between the groups to build a vaccine first. Media stories sometimes framed this as a quest for profit, but the real race, Green and Gilbert repeatedly emphasize, was always against the virus and its mounting death toll, not the other groups.

Leap into action

The Oxford–AstraZeneca story begins around 2014, as Gilbert hops between grants and contracts at Oxford, scraping together laboratory funds. They look for ways first to develop an Ebola vaccine and then to prepare for a future epidemic “Disease X”. The identity of this illness was uncertain, but its eventual arrival was never in doubt.

Soon after news of SARS-CoV-2 arrives in early January 2020, Gilbert and Green decide that COVID-19 could be Disease X. They risk their reputations and a substantial amount of Oxford’s money to prepare a vaccine, even before the need becomes clear. Although I have reported on many aspects of COVID-19 vaccine development over the past year, I was surprised to learn the extent to which they had to gamble in those early days, without knowing if funding would come through — and that the vials of vaccine used in the first clinical trials were filled by hand at Oxford’s facility.

From April, a collaboration with AstraZeneca boosts their manufacturing capabilities. But it comes with a dash of culture clash between the small, nimble academic lab and the corporate behemoth. This collaboration, as well as one with the Serum Institute of India in Pune, and an early insistence on minimizing the price and making the vaccine available to the world, have helped to ensure that Gilbert and Green’s early gambles have global impact.

There are details about some of the more frustrating moments in the Oxford–AstraZeneca vaccine’s development. This includes an explanation of why some clinical-trial participants received different amounts of vaccine, and waited for different lengths of time between doses. Both of these incidents complicated interpretation of study results.

Other key moments get less attention. There is no reference to South Africa’s February decision not to use its doses of the Oxford–AstraZeneca vaccine, because the jab failed to prevent infections with the Beta variant of SARS-CoV-2 sweeping the region. And safety concerns over an extremely rare but potentially deadly blood-clotting disorder that might be associated with the vaccine are mentioned only briefly. Yet the resulting fears and roll-out pauses threw a huge spanner in the works.

Hidden heroes

Still, the book highlights the under-sung research behind vaccines, and the need to promote it. The authors repeatedly emphasize how development was accelerated not by skipping safety steps, but by taking financial risks, such as running various testing stages concurrently. Developers must usually ensure that one step is successful before moving to the next.

Throughout, food metaphors make the people and science relatable. The first viral cultures are like a sourdough starter; the conventional process of getting a lab result, then applying for funding for the next step, is like having to make a separate run to the shops for each ingredient in a roast dinner. The biggest mystery, ultimately, is how the authors found time to write the book in the middle of it all.

Although the chronology of events and science sometimes get jumbled — readers are given a detailed explanation of the chewy “replication-deficient recombinant simian adenoviral-vectored vaccine” well before they are introduced to the basics of how vaccines work — Green and Gilbert lay everything out clearly, from molecular biology to clinical-trial design. There is even a handy appendix listing the ingredients of the vaccine and what each does.

It would be wonderful if that were enough to quell the sort of concerns Green heard at the campsite. Sadly, it is hard to imagine that even her down-to-earth charm can compete with the flood of anti-vaccine propaganda that fills social-media feeds. Even so, it is worth a try.