Vaccine innovation in the UK: SMEs and national capabilities

THE 2013-2016 West African Ebola outbreak prompted an evaluation of the UK Government’s response to infectious diseases with epidemic potential, which resulted in the creation of the UK Vaccine Network (UKVN). The UKVN is a £110m project that is part of the Department of Health and Social Care (DHSC) Global Health Security programme. It supports the development of new vaccines and vaccine technologies to tackle diseases that represent emergent epidemic threats, for the benefit of people in low- and middle-income countries (LMICs).

Since 2016, the DHSC has worked with UK Research and Innovation (UKRI) to fund R&D competitions for: a) the development of new vaccine platforms and manufacturing techniques; and b) late-stage pre-clinical and early-stage clinical development of vaccine candidates for 12 priority pathogens previously identified by the UKVN. Although the COVID-19 virus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) was not included in the list, another member of the coronavirus family, the Middle Eastern Respiratory Syndrome (MERS) virus was.^1,2 More importantly, the focus on the development of novel vaccine platforms enabled UK academic and industrial groups to employ these technologies to develop anti-COVID-19 vaccines.

Funded by the UKVN, Professor Robin Shattock’s group at Imperial College London developed a multivalent synthetic self-replicating RNA (saRNA) platform technology as a safer, faster and more cost-effective approach to the development of vaccines against human viral haemorrhagic fevers. The ultimate aim of the project was to develop this platform for future pandemics, which became a reality in 2020 as the platform was used to develop one of the UK’s two leading vaccine candidates against COVID-19. In June 2020, Imperial College London set up a social enterprise, VacEquity Global Health, in partnership with Morningside Ventures to manufacture and distribute this vaccine in the UK and overseas, including LMICs.

The technology behind the UK’s leading vaccine candidate, AZD1222, was also supported by UKVN. It was developed by scientists at the University of Oxford and Vaccitech, led by Professors Sarah Gilbert and Adrian Hill and licensed to AstraZeneca. It combines the knowledge on clinical development and manufacturing from AstraZeneca and the safety and immune response data gained by the development of vaccines against other viruses, including MERS, by the University of Oxford/Vaccitech.³

In 2018, the UK Government Industrial Strategy Challenge Fund (ISCF) invested £66m in the creation of the Vaccines Manufacturing Innovation Centre (VMIC), which is currently being built in Oxfordshire. The centre is also backed up by private investment from Janssen Vaccines & Prevention and MSD, as well as expertise and training from Cytiva.⁴ In response to COVID-19, the UK Government has invested a further £131m to accelerate the completion of the centre and create a temporary manufacturing facility (“Virtual VMIC”) ready to make vaccines at pace and scale to support the manufacturing of a COVID-19 vaccine when it is ready.⁵

Another COVID-19 initiative launched by the Government was the creation of a Vaccine Taskforce to rapidly manage the development and deployment of the vaccine. It has selected the two candidates described above.⁶ Both of these vaccines are now being tested in humans and the Taskforce has co-ordinated public and private sector organisations involved in their development and used the UK’s R&D expertise to support international vaccine efforts.

If everything goes according to plan, the Oxford/ AstraZeneca vaccine could be approved for human use later this year⁷ and subsequently made available for vaccinations in the UK and worldwide through agreements with organisations including CEPI, Gavi and the Serum Institute of India.⁸ The Imperial College London vaccine is expected to be ready for UK administration in early 2021.⁹

The vaccine innovation landscape in the UK has a rich diversity of university laboratories, research institutes and innovative companies working on prophylactic vaccines. Table 1 lists some of the UK SME innovators in this space and several will be highlighted below.

Technologies under development cover areas including novel vaccine design platforms, needle‑free delivery, technologies to eliminate the cold chain and “One Health”. As expected, many of these companies are involved in the development of COVID-19 vaccines and may provide new technologies for the next pandemic.

Traditionally, vaccines have contained weakened or inactivated whole pathogens – an approach which is still used successfully today. However, new tools including improved DNA sequencing, as well as better understanding of the immune system and increased computing power, have become available. They have allowed vaccine companies to build models to predict the immunological responses to vaccines (both humoral and cellular), and to assess parameters such as manufacturing yield and stability. This can help design optimal genetic sequences for vaccines tailored to the pathogen against which immunity is sought. Baseimmune is a UK SME focusing on this approach by using a variety of data sources: ’omics (genomic, proteomic, metabolomic, etc,) databases, laboratory data, surveillance data and others, and applying deep learning to derive vaccine candidates. Similarly, DIOSynVax aims to apply their computing platform using genomic and immunologic inputs to derive DNA- or RNA‑based vaccines.

If a vaccine is based on genetic information encoding immunogenic fragments of the pathogen, it usually needs a vehicle to introduce this into the recipient’s body. The Oxford COVID-19 vaccine, with the involvement of SME Vaccitech, is an example of this. The team has developed a non-pathogenic chimpanzee adenovirus delivery system that, in the case of AZD1222, incorporates the genetic information of the SARS-CoV-2 Spike protein, which is essential for the COVID-19 virus to enter target cells. Its intention, following administration of the vaccine, is for the recipient to express this protein antigen and mount an effective immune response against it.

Building synthetic particles that resemble viruses and that incorporate pathogenic antigens is an alternative novel way of designing vaccines. This approach aims to mimic either enveloped or nonenveloped viruses, called virosomes and virus‑like particles (VLPs), respectively. Activirosomes is an SME working on the former. Its lipid vesicle technology, Active Virosome, is aimed at developing effective, affordable vaccines to respond quickly to new infection outbreaks. This is achieved by introducing antigens or genetic constructs into these vesicles. An example of the latter is SpyBiotech, which has developed technology that avoids one of the challenges of VLPs: a lack of stability. This instability arises due to the incorporation of antigens derived from pathogens into VLP structural proteins. SpyBiotech has designed stable structural VLP proteins incorporating a tag called SpyCatcher. This forms an irreversible bond with the target antigen incorporating another tag called SpyTag. This technology ensures complete coverage with immunogenic antigens of the particle. New vaccines can be generated by exchanging the antigen onto a universal particle platform.

An additional area of focus is oral delivery of vaccines, as mucosal delivery may generate a more effective immune response. They are also easier to administer. Examples include iosBio and SporeGen. iosBio’s OraPro platform consists of a non-replicating viral delivery vehicle formulated in an enteric capsule for oral administration. The advantages of OraPro include cold chain-free distribution and storage, the ability to withstand the acidity of the stomach and delivery in a non‑invasive manner. They also claim the potential for repeat dosing due to a lack of anti-vector immunity in the gastrointestinal tract and the possibility of combined delivery of vaccine antigens and other biopharmaceuticals using their platform. SporeGen’s SporeVax^® approach is to display vaccine antigens on the surface of spores derived from Bacillus subtilis. The spores act as vaccine delivery agents and can survive temperatures as high as 70°C.

Finally, another important angle worth mentioning is One Health. The WHO defines One Health as “an approach to designing and implementing programmes, policies, legislation and research in which multiple sectors communicate and work together to achieve better public health outcomes”.¹⁰ In the context of vaccines, this includes controlling zoonoses: diseases that can spread between animals and humans. Examples are new, more pathogenic human influenza variants generated within an animal vector, which then move to infect humans. The Vaccine Group addresses this – using a herpes virus-based delivery system, the company has developed vaccines for zoonotic diseases including COVID-19, for which the company is hoping to start field trials in cats and other pets.

In addition to the innovative SMEs described above and in Table 1, the complexity of developing vaccines requires a matching complex mix of organisations including academic institutions, large biopharmaceutical companies, contract researchers, development and manufacturing organisations, funders, membership organisations and research and technology organisations (RTOs). The latter play a key role in facilitating the translation from early-stage product to market introduction. Besides VMIC, other major UK RTOs supporting vaccine development are the Cell and Gene Therapy Catapult, whose particular expertise is in viral delivery vehicles, and the Centre for Process Innovation (CPI) site in Darlington, which specialises in biologics manufacturing, including vaccines. Their roles in the two main government‑backed vaccines include CPI working with the Imperial College London team on their vaccine¹¹ and the Cell and Gene Therapy Catapult managing the conversion and operation of an existing vaccine facility for the purpose of COVID-19 vaccine manufacture.¹²

In summary, the UK is well placed to develop safe and effective vaccine candidates to COVID-19. As a result of the timely investments described in this article, the country is also poised to play a leading role in the response to future epidemics.

References

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3. University of Oxford. COVID-19 Oxford Vaccine Trial. Available from: https://COVID19vaccinetrial.co.uk/about [Accessed 5th October 2020].
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8. AstraZeneca. AstraZeneca takes next steps towards broad and equitable access to Oxford University’s potential COVID-19 vaccine. Available from: https://www.astrazeneca.com/mediacentre…[Accessed 5th October 2020].
9. Scheuber A. Imperial social enterprise to accelerate low-cost COVID-19 vaccine. Available from: https://www.imperial.ac.uk/news… [Accessed 5th October 2020].
10. World Health Organization. One Health. Available from: https://www.who.int/news-room/q-a-detail/one-health [Accessed 6th October 2020].
11. CPI. CPI joins national taskforce to develop COVID-19 vaccine. Available from: https://www.uk-cpi.com/news… [Accessed 6th October 2020].
12. Cell and Gene Therapy Catapult. Press Release: Over £100m cash boost to manufacture millions of doses of COVID-19 vaccine. Available from: https://ct.catapult.org.uk/news-media/general-news/press-release… [Accessed 6th October 2020].