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Studies carried out in the MRC Human Immunology Unit (MRC HIU) in collaboration with the Pirbright Institute have shown that a 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.

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.

Dr Jack Tan, from the Townsend group at the MRC HIU, said: “We were fascinated by the SpyTag/SpyCatcher technology developed by Mark Howarth and our work together since led to the development of the RBD-SpyVLP vaccine. RBD-SpyVLP is very potent and extremely stable at room temperature. It can be freeze-dried, which will greatly facilitate its distribution in countries with insufficient cold-chain capacity. The vaccine is also versatile and can be updated to match the circulating variants promptly. We are trying very hard to obtain funding at the moment and hoping to test the RBD-SpyVLP in human in the near future.”

Professor Graham Ogg, Interim Director 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."

 

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