Studies carried out by The Pirbright Institute and the University of Oxford have shown that Oxford’s new potential vaccine against COVID-19, named RBD-SpyVLP, produces a strong antibody response in mice and pigs, providing vital information for the further development of the vaccine. Although this type of vaccine is not a competitor for the first wave of vaccines, it is hoped that it will be useful as a standalone vaccine or as a booster for individuals primed with a different COVID-19 vaccine.
Having already taken over two million lives, the COVID-19 pandemic continues to have a huge global impact on human health, welfare, and economies. The need for a vaccine against the virus that causes the disease, SARS-CoV-2, has become increasingly urgent and the global research community has risen to the challenge. Vaccine development has progressed at an unprecedented pace, with the World Health Organization (WHO) reporting 173 vaccine candidates in preclinical trials, 64 that have moved to human clinical trials and three that have received temporary authorisation for use in the UK.
The Oxford-produced RBD-SpyVLP vaccine candidate contains part of the SARS-CoV-2 spike protein called the receptor binding domain (RBD), which a range of protective neutralising antibodies can bind to in a way that blocks infection. The RBD is attached to a virus-like particle (VLP) that contains no genetic material using Oxford’s SpyTag/SpyCatcher technology, a kind of protein ‘superglue’. This was shown to generate a greater antibody response in mice than administering the RBD alone. Pirbright researchers tested the RBD-SpyVLP vaccine in pigs as a large animal model to establish if different dosages would affect the immune response.
The research, published in Nature Communications, demonstrated that RBD-SpyVLP produces a strong neutralising antibody response. The study also examined samples taken from the nose and mouth of vaccinated pigs and found SARS-CoV-2 specific antibodies were present. This is a promising finding since antibodies at the site of entry for SARS-CoV-2 could be important for providing robust protection. Interestingly, no difference was found in the magnitude of antibody response when comparing vaccine dose levels. This suggests that the smaller dose tested, which is the same as intended for human administration, may provide equal protection to larger doses or that even lower doses of the vaccine could be effective.
Pirbright’s pig model has previously been used to test Oxford’s ChAdOx1 nCoV-19 (AZD1222) vaccine, which demonstrated that two doses produced a stronger immune response in pigs than one. Pigs have similar immune, respiratory and physiological characteristics to humans, and can therefore provide vital knowledge about the response to candidate vaccines that can inform human clinical trials. This model has been shown to predict vaccine outcome in humans, particularly in influenza studies.
Professor Simon Graham, who led the pig studies at Pirbright, said: “These results offer valuable insights into the kind of immune responses that the RBD-SpyVLP vaccine could trigger in humans. Further understanding the dose required to elicit a strong immune response is key for the progression of vaccine development and scaling up for manufacture.”
The researchers also tested the stability of the vaccine and found that RBD-SpyVLP is highly resilient, stable at room temperature and can be freeze dried without losing its power to immunise. These properties would reduce dependence on cold chains for transport and storage and facilitate global distribution.
Professor Graham Ogg, Interim Director of the Medical Research Council Human Immunology Unit (MRC HIU), remarked: “I am delighted about the promising progress of the novel vaccine study, which is a result of a large collaborative effort including Professor Alain Townsend’s team at the MRC HIU, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford and The Pirbright Institute. The findings provide the foundations to progress towards further exciting developments.”
Professor Melanie Welham, Executive Chair at the Biotechnology and Biological Sciences Research Council (BBSRC), part of UK Research and Innovation (UKRI) said: "These latest results into the immune response from the Oxford COVID-19 vaccine candidate, RBD-SpyVLP, are both exciting and promising. By drawing on scientific knowledge from multiple disciplines, researchers have collectively demonstrated the ability to improve and advance development of the vaccine."
Notes to editors
The article “A COVID-19 vaccine candidate using SpyCatcher multimerization of the SARS-CoV-2 spike protein receptor-binding domain induces potent neutralising antibody responses” will be available in Nature Communications from 10:00 GMT on the 22 January 2021.
Research was funded by the Townsend-Jeantet Charitable Trust, the EPA Cephalosporin Early Career Researcher Fund, the Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Science (CIFMS), Cancer Research UK, the UKRI Medical Research Council and the Wellcome Trust (FC001030).
The Pirbright Institute research was funded by the Biotechnology and Biological Sciences Research Council (BBSRC) UK Research and Innovation (UKRI) Institute Strategic Programme Grants, the UKRI Engineering and Physical Sciences Research Council and the UK Department for Environment Food and Rural Affairs.
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About The Pirbright Institute
The Pirbright Institute is a world leading centre of excellence in research and surveillance of virus diseases of farm animals and viruses that spread from animals to humans. Based in the UK and receiving strategic funding from the Biotechnology and Biological Sciences Research Council (BBSRC) part of UK Research and Innovation (UKRI), the Institute works to enhance capability to contain, control and eliminate these economically and medically important diseases through highly innovative fundamental and applied bioscience.
The Institute is an independent company, limited by guarantee and a registered charity, governed by a Board of non-executive Trustee Directors.
With an annual income of £35 million from grants and commercial activity, and a total of £25.2 million strategic investment from BBSRC UKRI during 2019-2020, the Institute contributes to global food security and health, improving quality of life for animals and people.
For more information about The Pirbright Institute see: www.pirbright.ac.uk
About the Medical Research Council Human Immunology Unit (MRC HIU)
The Medical Research Council Human Immunology Unit (MRC HIU) was founded in 1998 and represents one of the central pillars of basic and translational immunology in Oxford, and also throughout the UK and worldwide. The MRC HIU encompasses a broad range of inter-related research programmes which further our understanding of how the human immune system functions from early life to old age, and during health and disease. Such knowledge is critical in the development of new approaches to prevent and treat infections, autoimmune diseases and cancer. The MRC HIU team are directly involved in clinical trials to translate the findings towards patient benefit.
About BBSRC UKRI
The Biotechnology and Biological Sciences Research Council (BBSRC) is part of UK Research and Innovation (UKRI), a non-departmental public body funded by a grant-in-aid from the UK government.
BBSRC invests in world-class bioscience research and training on behalf of the UK public. Our aim is to further scientific knowledge, to promote economic growth, wealth and job creation and to improve quality of life in the UK and beyond.
Funded by government, BBSRC invested £451 million in world-class bioscience in 2019-20.
We support research and training in universities and strategically funded institutes. BBSRC research and the people we fund are helping society to meet major challenges, including food security, green energy and healthier, longer lives. Our investments underpin important UK economic sectors, such as farming, food, industrial biotechnology and pharmaceuticals.
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