Dr Sarah Gilbert is a Professor of Vaccinology in the Jenner Institute, Nuffield Department of Medicine at the University of Oxford and has been leading the Oxford Vaccine Trial for COVID-19. In this interview, she talks about the trial and what the different phases entail. Moreover, she discusses how her background in vaccine development and experimentation for infectious diseases such as MERS has informed her current work on COVID-19 and addresses what is unique about the ChAdOx1 nCoV-19 vaccine compared to her previous experiences. In addition she talks about the challenges faced by the research community at this time and the role of researchers.
More than 1000 participants were recruited into the phase I trial, and phase II started at the end of May to increase the upper age limit to 70, and then to over 70 during June. The phase III trial which is aiming to recruit 10,000 participants also started at the end of May. In all of the trials, participants receive either ChAdOx1 nCoV-19 or a meningitis vaccine and they don’t know which they received. If they experience symptoms of COVID-19 they get a PCR test to see if they have been infected. When enough people have been infected it will be possible to work out if the vaccines works, and how well. We now need to finish vaccinating the older age groups in phase II and all of the people in phase III, take some blood samples so we can look at immune responses and wait to see if people are infected.
There is a huge sense of urgency, which is understandable during a pandemic. Removing bottlenecks to progress has been the approach taken by everyone. How can we do everything that we need to do, to the required standards, but without causing any unnecessary delays? It helps that the team working on this is very experienced in vaccine development, so between us we all understand what needs to be done and where delays can creep in.
With colleagues, ChAdOx1 has been used to develop candidate vaccines against many diseases including several emerging pathogens (MERS, Chikungunya and Zika clinical trials had all started). Twelve clinical trials had either been completed or were underway and several hundred people had been vaccinated. So we had a lot of information about the dose to use, likely reactions to vaccination and immune responses, as well as how to manufacture the vaccine and what tests needed to be completed. All of that meant we were ready to move quickly for COVID-19.
We expect to detect infections in vaccine trial participants more quickly in Brazil and South Africa than the UK, so we will potentially see results sooner. But that will depend on the amount of virus transmission in those countries next month, when people have been vaccinated, rather than now. Transmission could go up or down, including in the UK.
At Oxford, we are doing the kind of research we have all done before. But in these days of unprecedented urgency, activities that would normally follow on from one another all have to be dealt with at the same time. We are working on large scale manufacturing before we know if the vaccine works, so that we don’t have a delay later on.
Vaccinology is a very broad discipline requiring input from multiple experts, so we are used to collaborating widely. That also means we have specialists on hand to help us with all the necessary contracts with external partners. Without them we wouldn’t be able to work with so many partners.
As yet there are no widely available standardised immunology assays. We need these so that results from one study can be compared with those from another. I have seen comments comparing antibody levels in preclinical studies but these are meaningless because every study is measuring the antibody levels in a different way. At the moment the assays are telling us that, for example, neutralising antibodies are induced by vaccination, but we can’t compare levels across studies. Work is underway to establish core labs and standardised assays but those things don’t happen overnight. Once the set-up work has been done it will be important for all vaccine developers to report data from standardised assays.
There has been a great deal of collaboration rather than competition, which is helping scientists across the world. This is something we should continue with in the future to solve other global health problems.
Publishers are facing the same challenges that we are in vaccine development, needing to work very quickly but without reduction in quality. So again it’s about following the normal procedures but accelerating the timelines without letting the quality be affected.
"Publishers are facing the same challenges that we are in vaccine development, needing to work very quickly but without reduction in quality."
For those of us already working in the field of emerging pathogen vaccines, the economic consequences of the pandemic are not surprising, but in the wider world the impact that a virus can have on every aspect of our lives has only now been recognised. In future, we need to invest more in preparedness to reduce the impact of the next pandemic, or to even better, prevent the next outbreak from becoming a pandemic.
"In future, we need to invest more in preparedness to reduce the impact of the next pandemic, or to even better, prevent the next outbreak from becoming a pandemic."
At the moment with everything moving so quickly it is difficult to think past the next few days. I am receiving invitations to speak at conferences next year, and it seems impossible to consider something so far into the future. Of course there are going to be long term impacts, and some of them will change our lives in a positive way. I think there will be much more use of video conferencing in general, and a reduction in travel for meetings. But there is value in being able to meet in person at scientific conferences, and often great collaborations start after an informal interaction at a conference dinner, so I hope that it will be possible to return to some in-person meetings.
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Sarah Gilbert is a Professor of Vaccinology in the Jenner Institute, Nuffield Department of Medicine at the University of Oxford. For more than 20 years she has been working on the development of platform technologies for vaccine development, including DNA vaccines, poxvirus and adenovirus-vectored vaccines. After working on the development of vaccines against malaria and influenza, following the Ebola outbreak in 2014 she began to work on the development of vaccines against emerging pathogens, including Middle East Respiratory Syndrome (MERS), Nipah, Lassa, and Crimean Congo Haemorraghic Fever. Additionally work to prepare for ‘disease X’ paved the way for the rapid early development of ChAdOx1 nCoV-19 beginning in January. Dr Gilbert has also published with Scientific Reports (Modification of Adenovirus vaccine vector-induced immune responses by expression of a signalling molecule and Humoral Immunogenicity and Efficacy of a Single Dose of ChAdOx1 MERS Vaccine Candidate in Dromedary Camels) and Nature imprints (Protective CD8+ T-cell immunity to human malaria induced by chimpanzee adenovirus-MVA immunisation and Recombinant modified vaccinia virus Ankara expressing antigen 85A boosts BCG-primed and naturally acquired antimycobacterial immunity in humans).