On International Day of Immunology, the British Society for Immunology published a new report, ‘Protecting the world: Celebrating 200 years of UK vaccine research’. Through new analysis and expert interview, our report reviews the UK's outstanding contribution to vaccine research and how this has improved global health. It also looks at future challenges that must be overcome to speed up the vaccine development pipeline to bring new vaccines to tackle existing and emerging disease.
Over the past couple of years, the cornerstone of the BSI’s policy and public affairs programme has been our work to improve vaccination uptake and tackle the origins behind this trend. We were delighted, therefore, to be chosen as a partner organisation to support the replenishment of Gavi, the Vaccine Alliance, by utilising our status as a voice for research.
The report lays out the rich tradition of vaccine research in the UK, from Edward Jenner’s smallpox vaccine to 2020’s endeavour to develop a vaccine against COVID-19, and explores the obstacles and challenges that face the sector at the moment, while championing the impact that vaccines themselves have both at home and abroad.
It became clearer during writing the report that there is mutualistic symbiosis between funding for the UK’s international development efforts and for UK vaccine research and that by helping one, we help them both. The news that came two hours after the report was released – that the Secretary of State of International Development announced that the UK will continue its funding of Gavi to the equivalent of £330 million every year for the next five years - is therefore a cause for celebration, not just for international public health but also for UK vaccine research.
In our report, we highlight the critical role that the immunology community plays in delivering these benefits and why longterm strategic funding of vaccine research is vital.
What did we find?
Today’s vibrant UK bioscience ecosystem fosters effective collaboration between industrial, academic, charitable and government-funded research, leveraging global connections to bring novel vaccines to the places that need them most.
- UK immunity research is world-leading, topping the G7 for impact and influence, boasting a 68% increase in immunity publications between 2008 and 2017. Despite being home to just 9% of the G7 population, the UK produces 14% of its immunity research publications.
- We need to continue our global record in vaccine research, which remains highly valued internationally, being the second most cited country of the G7 by the WHO, as well as being the most often cited by the UK Government. It is crucial that we continue to provide the vaccine research sector the resources that they need to maintain their global leading status.
- Living in a globalised world increases the threat of disease but bolsters our response. The global COVID-19 pandemic clearly demonstrates that public health issues are global events. But, globalisation provides an excellent platform for international scientific collaboration to develop vaccines against diseases that threaten us all.
UK research is leading the world
The UK has been at the cutting edge of science for centuries, and research into immunity and vaccination is no exception. From understanding the immune system to tracking infections, developing new vaccines to life-saving clinical trials, our researchers are making a major contribution to global progress in public health.
Despite its relatively small size, the UK punches well above its weight when it comes to producing worldleading research, particularly around the science underpinning immunity. When comparing UK immunity research performance with other G7 countries, the UK consistently outperforms its peers in terms of the volume and influence of research outputs relevant to vaccines.
The UK contains around 9% of the G7 population, and yet produces 14% of the G7’s scientific publications in immunity. The UK also leads the G7 in terms of the impact of these publications, indicated by the number of times the results are cited in other research papers. UK publications on immunity are cited on average 29.3 times. The UK’s Fields Citation Ratio, a measure of the scientific influence of those publications, is also the highest of all G7 countries.
In 2017 the UK published 8,630 scientific papers in immunity, an increase of almost 68% from the 5,141 published in 2008, making the UK the fastest growing country of the G7 in this area. However, research specifically focusing on vaccines is lagging behind immunity research in the UK in terms of performance and influence.
At a time when the world is acutely aware of the threats posed by emerging diseases, it is concerning to see that the number of grants awarded for vaccine research and development in the UK appears to have taken a downturn over recent years. When vaccine research is more important than ever before, we must ensure that efforts are being undertaken to bring vaccine research to parity with the rest of the immunity sector. The effect of the recent downturn in grants being made to vaccine research is yet to become clear.
A report by the All Party Parliamentary Group on Global Health, published in February 2020, also highlighted the quality and impact of UK research, placing the UK at the top of the G7 across multiple health research disciplines, including immunology.
Immunology research was shown to outperform other health research disciplines in the UK, with a higher citation score than the UK’s public health and healthcare sciences sectors. UK immunology also ranked higher among the G7 compared with our research and experimental medicine sector. The same report estimated that the UK’s investment in Gavi, the Vaccine Alliance, between 2016 and 2020 enabled 76 million children to be vaccinated and saved 1.4 million lives.
According to the WHO, Gavi has averted medical costs of $350 billion and brought $820 billion in economic and social benefits since 2000 across the 73 countries it has operated in. The importance of vaccine research to patient benefit, not just in the UK, but across the whole world is clear. It is evident that maintaining the UK’s status as the engine room of immunity research and levelling up its vaccine research sector is key to increasing the number of diseases which we can protect ourselves against using vaccines.
Working together for global health
Throughout the 20th century, UK researchers have built a strong network of international collaborators and partnerships, although it has tended to be focused on a relatively small number of countries. As our world becomes increasingly connected, bringing new opportunities for international scientific exchanges and training, it’s easier than ever before to forge partnerships and collaborations wherever they are needed.
In the past, many vaccine research projects in lower-income countries – where many of the studied diseases are endemic, were carried out by visiting teams of European or American scientists. Today, most of the pioneering research projects and papers published on vaccine research have a long list of scientists and institutional partners drawn from many countries, including across Africa and Asia. Working together with scientific organisations in these regions enables UK researchers to share expertise and resources, and creates new opportunities to empower and upskill local scientists.
UK research brings vaccines where they’re needed
New vaccines are often developed in higher-income countries like the UK and do eventually reach low- and middleincome countries (LMICs), but logistical and financial challenges mean that this process can take a long time. For example, the first conjugate pneumococcal vaccines were licensed in Europe twenty years ago, but they still are not available everywhere.
UK research and funding are vital for speeding up the availability of vaccines in LMICs. International organisations like Gavi, the Vaccine Alliance, have been instrumental in making vaccines commonplace in these countries, with strategic funding from the Wellcome Trust and MRC also working together for global health playing a significant role. These efforts have increased vaccine coverage globally, with 86% of infants worldwide now receiving the diphtheria-tetanus-pertussis vaccine.
Harnessing the ‘network effect’
Current vaccine development pathways are expensive, complicated and convoluted, with each new product often taking 10–15 years to come to fruition. Delays and challenges during the development process can stop life-saving vaccines from ever making it to market. Networks that bring together international experts from industry, academia, philanthropy and government can help overcome these roadblocks and deliver crucial vaccines where they are needed most.
We have been amazed by the sheer enthusiasm for the Network among our international colleagues. It has grown extraordinarily rapidly, and we now have members in around fifty countries all over the world - Dr Beth Holder, IMPRINT Network
Despite the challenges associated with coordinating such large international networks, they have been very successful and sprouted collaborations that have impacted research around the globe. Besides bringing together experts to share ideas and resources, the networks also provide small research grants for overcoming research hurdles or generating pilot data. They also play a vital role in building research capacity in LMICs by providing post-doctoral fellowships, collaboration opportunities and training for early-career researchers.
From Nepal to the world
Professor Andrew Pollard from the University of Oxford has been tracking infectious diseases in Nepal for 15 years. After identifying typhoid as one of the commonest killers of under-fives in the country, he and his collaborators developed a new conjugate typhoid vaccine that was first tested in the UK and manufactured by the Indian company Bharat Biotech International.
The vaccine underwent large-scale trials in Nepal and elsewhere in Asia and Africa, with interim results showing that it reduced typhoid infections by an impressive 82%. In 2019, the vaccine was employed by the Pakistani health authorities to tackle an outbreak of antibiotic-resistant typhoid. Following its success, the vaccine is now being rolled out to many more countries including Zimbabwe and Liberia, supported by Gavi, the Vaccine Alliance.
An army of African scientists
Professor Faith Osier is a group leader at the KEMRI-Wellcome Trust Research Programme in Kilifi, Kenya, where she’s working on promising malaria vaccine candidates. She established the SMART consortium, bringing together scientists from seven African countries to share resources, training and data to support malaria vaccine research.
My heart beats for the science in Africa - Professor Faith Osier, Group Leader, KEMRI-Wellcome Trust Research Programme
Osier also works closely with UK institutions, including the Wellcome Sanger Institute, the University of Cambridge, the University of Oxford and the London School of Hygiene and Tropical Medicine. “Our collaborators in the UK provide access to high-end technology that we do not have or that we cannot get working quickly here, including technologies like sequencing, proteomics, and structural biology,” she says. “They also support the training of African scientists, allowing students to visit and work in their laboratories and learn new technical skills.”
“My heart beats for science in Africa,” Osier admits “We need African scientists to work to eradicate diseases in Africa. I have a vision that African researchers can be involved in vaccine development from the beginning of discovery, to upscaling, conducting trials, regulation, and right through to the end of the process. To do that, we rely on our well-resourced colleagues to support their education and training.”
The hunt for a COVID-19 vaccine
On 31 December 2019, health authorities in Wuhan, China, reported a cluster of patients with cases of pneumonia with an unknown cause to the WHO. The disease was eventually named COVID-19 and a novel coronavirus, SARS-CoV-2, identified as the virus behind it. The virus rapidly spread, infecting millions worldwide in a matter of months. Many countries have introduced restrictive measures such as social distancing or lockdowns to contain or slow the spread, protect vulnerable populations and avoid overburdening healthcare services.
Despite these efforts, protecting the population through widespread vaccination will be the only way to beat the disease in the long term. By the end of March 2020 there were already more than 40 vaccine candidates in development from academic groups, established pharmaceutical companies and start-ups in many countries. This number had grown to at least 70 by the middle of April as more organisations joined the international research effort. Some are created from genetic material (RNA or DNA) derived from SARS-CoV-2, while others are based on fragments of its proteins.
UK vaccines in development
We were able to go from having the virus’ genetic code to building a prototype vaccine and our first animal experiments within three weeks. In animals, the vaccine induced very potent neutralising antibodies with a single immunisation - Professor Robin Shattock, Imperial College London
The UK is at the forefront of vaccine research efforts with two groups in particular advanced in their efforts:
- Scientists at the University of Oxford, led by Professor Sarah Gilbert, are developing a vaccine that uses a harmless weakened virus from chimpanzees to deliver Coronavirus RNA into cells in the body. Once the cells receive the RNA they produce viral proteins, which stimulate the immune system to generate protective antibodies against future Coronavirus infection. Similar experimental vaccines have already been tested in early stage clinical trials against MERS (Middle East Respiratory Syndrome), proving that this technique is safe for use in humans. Clinical trials of the virus-based SARSCoV-2 vaccine are starting in April 2020.
- At Imperial College London, Professor Robin Shattock and his team are working on a more experimental ‘plug and play’ approach, creating a vaccine made from selfamplifying RNA encapsulated in tiny droplets. This vaccine contains genetic instructions encoding both the virus spike protein (the part most likely to induce an immune response) and RNA copying machinery, enabling the vaccine to self-replicate inside cells and generate a greater protective immune response. The Imperial team expects to start clinical trials in June 2020.
Next steps for Coronavirus vaccine research
All of the vaccines in development must first prove they are safe and effective in small-scale clinical trials, which could take many months. Next come the challenges of scaling-up manufacturing and larger clinical trials involving hundreds or thousands of people before widespread rollout.
This will be no small feat: vaccines are commercially risky investments for pharmaceutical companies and production facilities are generally designed to produce one specific vaccine. The scaling-up of infrastructure to manufacture any new vaccine will be a very serious challenge.
There are still many questions about COVID-19 that need to be answered as we progress towards effective vaccine implementation: How long does immunity last and how many doses will be needed? Does protection vary between people according to genetic background, age or sex? And who should get priority access to vaccination in order to most effectively protect vulnerable populations?
The underlying aim of our report was to champion the UK vaccine research sector to policymakers, while making the case for the UK to make another substantial multiyear investment in Gavi, the Vaccine Alliance, ahead of their next replenishment conference in June, to be hosted virtually by the UK. A few hours after the report was launched, the Secretary of State for International Development announced in Parliament that the UK Government has decided to fund Gavi to the equivalent of £330 million per annum for the next five years. Meanwhile, our report had been sent to all MPs, all peers, a number of civil servants in Whitehall and officials in Parliament, as well as our partner scientific and civil society organisations.
We have had a number of leads from this work which are being followed up, not least the opportunity for working with Lord Patel, Chair of the House of Lords Science and Technology Committee on their next parliamentary inquiry on SARSCoV-2. This is a piece of work which will have longevity; many of the statistics produced for it will continue to inform our conversations with policymakers for months and years to come, and we will keep you updated on all our progress.
BSI Policy & Public Affairs Manager