Medicine and wellbeing
I feel grateful I’ve been able to contribute
For the past 19 years, David Turner has combined teaching and research at the School of Life Sciences with clinical duties as an honorary Consultant Microbiologist at Nottingham University Hospitals NHS Trust. In March and April 2020, in the first wave of the pandemic, he switched to 100% hospital work to support the intensive care team at Queen’s Medical Centre, who were facing a rising tide of patients suffering from Covid-19.
Adult males, typically over 50 years, with relatively mild and stable co-morbidities such as hypertension or type 2 diabetes or who were moderately overweight, were at particular risk. Dr Turner advised ICU colleagues on antibiotic therapy for many such patients who were struggling with severe lung infection due to the SARS-CoV-2 virus.
The veteran researcher recalls: “It was clear this was a really severe infection.” He also knew that only an effective vaccine offered a way out of this terrible situation and a long-term solution to the global crisis.
At the time, his research work looking at the effectiveness of meningitis vaccines in adolescents was nearing completion. The national study was led by the Oxford Vaccine Group at the University of Oxford, who at the time were beginning to develop the Oxford AstraZeneca vaccine.
“We’d been working with them for almost two years and they knew we were capable of delivering a large vaccine trial. When they asked if I could help with the development of a vaccine against Covid-19, I said: absolutely, yes.”
This was a new vaccine technology, he explains, using a genetically modified adenovirus as the platform for a vaccine to train the immune system to recognize the spike protein on the surface of the SARS-CoV-2 virus. The same technology had previously been used to develop a vaccine against another coronavirus infection that causes the Middle East Respiratory Syndrome (MERS).
"By switching the spike protein from MERS to SARS-CoV-2, the virus that causes Covid-19, we could have a vaccine. "
“We set up the trial in Nottingham during May and by the beginning of June had recruited the first participants, which is ridiculously fast. We went on to develop a vaccine and roll out a mass vaccination programme in less than 12 months. That's just never been done before.
“We effectively concertinaed the trial – the phase II/III trial was started before the phase I study was completed.”
To get the data needed in such short time frames, the Nottingham trial targeted volunteers at high risk of acquiring Covid-19. Dr Turner turned to colleagues working in the NHS in the city – porters, nurses, doctors, physiotherapists – the frontline staff potentially exposed to the virus on a daily basis.
Their blood samples and support for the trial – further testament to our healthcare workers’ remarkable sense of public service – provided an early indication that the vaccine worked. These phase I data also indicated the efficacy of a two-dose strategy. Phase II/III participants were offered a second dose and were asked to take weekly throat swabs to look for asymptomatic infection. The results indicated the vaccine reduced carriage of the virus and asymptomatic infection as well as reducing the incidence of serious disease or symptomatic infection.
By working in parallel with Nottingham and the other UK study sites, the Oxford team was able to watch the data accumulate in real time and towards the end of 2020 the interim data was very positive, showing the vaccine was highly effective at preventing symptomatic infection.
Dr Turner also stresses that safety remains paramount in the ongoing study. “We'd already accumulated a lot of safety data by following people in the study, asking if they had any side effects. We were very carefully to collect detailed information needed would require for safety and efficacy.
"After six months we followed up people who had the vaccine and will do so again after 12 months. We look for longer-term antibody levels and T-cell responses to see how the immune system responds over time."
The study in Nottingham was run from Cripps Health Centre, home of the University of Nottingham Health Service. Dr Turner and his team worked with GPs and nurses who administered the trial vaccines, while Nottingham University Hospitals NHS Trust processed, stored and shipped blood samples to Oxford.
School of Life Sciences Senior Research Fellow Dr Neil Oldfield, a long-time vaccine studies collaborator with Dr Turner, coordinated samples from well over 500 participants, and oversaw the lab work.
School of Life Sciences Immunologists, Paddy Tighe and Alex Tarr, had meanwhile set up an assay to detect Covid-19 antibodies, to screen out from the trial individuals who already had Covid-19 infection, before the NHS had such a test available.
“They worked throughout each evening to midnight to have the results available to us by morning. It eased a potential bottleneck at this crucial early stage of the study and we're really grateful to them.”
In addition to the primary Oxford vaccine study, Dr Turner is also collaborating with another team at Oxford, led by Matthew Snape, on What's the story?, a study looking at Covid-19 antibodies in children and young adults. It confirms children aged 14 and older are far more likely to get Covid-19 then younger children, who are more likely to have an asymptomatic infection.
Nottingham is also one of eight sites across the UK contributing to the world’s first alternating covid-19 vaccine study. The Com-Cov trial, which randomised recruits to either receive two doses of either the Oxford AstraZeneca or Pfizer vaccine, or a combination of the two, has since been extended to include the Moderna and Novavax vaccines. It will determine whether using a different vaccine for the second (booster) dose, in addition to two different intervals between doses, are as effective.
“With new vaccines continuing to be approved, if we show the immune response to mixed vaccine schedules is as effective as with the two doses of the same vaccine, then this could lead to more people being able to have their complete vaccination course more quickly. It will also reduce the risk of supply issues delaying vaccination.”
Such flexibility is paramount in the global fight against the virus. By offering countries access to different combinations of similarly effective vaccines, supplies will reach further.
New variants, from Brazil, South Africa and especially India are cause for concern. But results from the Oxford AstraZeneca and Pfizer vaccines are reassuring and scientists are cautiously optimistic that they remain robust against most variants. “They are very effective, safe and should lead to protection for a long period1,” says Dr Turner. “We've got probably one of the best vaccine rollout programmes in the world but for many other countries, this is going to be a massive undertaking, probably taking two or three years to vaccinate their populations. But I am optimistic that we have a good way out of this.”
For Dr Turner and his fellow researchers and clinicians, the past year has been truly challenging. It began with treating rising numbers of desperately ill people suffering from a new disease, to leading Nottingham’s contribution to the development and delivery, in record time, of a remarkably successful vaccine. A letter of thanks from Sir Patrick Valance, the UK’s Chief Scientific Advisor, highlighted their critical work, commitment and dedication in helping evaluate the Oxford vaccine, while the UK Vaccines Taskforce has expressed its “utmost gratitude”. Further ground-breaking studies in Nottingham are increasing understanding of Covid and will help secure long-term solutions to the global challenge of new viruses.
“I feel grateful - I've been able to continue to work throughout the lockdown, to do what I do both clinically and academically,” says David Turner. “It's a dreadful infection but professionally it's very gratifying to be able to contribute, from treating people with a completely novel, severe viral infection to helping to develop a vaccine with a completely new platform.”
Dr David Turner
Dr David Turner is Associate Professor in Clinical Microbiology in the School of Life Sciences and an Honorary Consultant Microbiologist at Nottingham University Hospitals NHS Trust.