Scientists at the University of Nottingham and Nottingham Trent University are to begin clinical trials for a DNA vaccine to prevent COVID-19.

Experts from both universities are working with Scancell Holdings plc, a developer of novel immunotherapies for the treatment of cancer, to adapt its existing cancer vaccine platform for the development of a new vaccine.

Now, thanks to funding from Innovate UK, as part of UK Research and Innovation’s response to COVID-19, work can progress to Phase I clinical trials.

Virologists at the University of Nottingham’s Centre for Research on Global Virus Infections have identified parts of the novel coronavirus, named SARS-CoV-2, that they hope will generate an immune response to prevent infections that have caused the COVID-19 pandemic.

This information is being used by Scancell to design DNA-based vaccines that allow easy and effective delivery of the vaccine into humans and the development of protective antibody and T cell immune responses.

Gene therapy scientists at the new University of Nottingham’s Biodiscovery Institute (BDI) are formulating the vaccine as peptide nanoparticles to be delivered efficiently with a simple injection. This will be scaled up to generate the dosages required for a global vaccination programme against COVID-19.

Nottingham Trent University’s John van Geest Cancer Research Centre will screen the new vaccine for its capacity to trigger immune responses against SARS-CoV-2, prior to the new approaches being tested in healthy volunteers.

There are usually four stages of clinical trials, with stage 1 being the first test in human volunteers. It is expected that these trials will begin next year, subject to available manufacturing capacity.

The project builds on Scancell’s success with its lead ImmunoBody® cancer vaccine to treat patients suffering from malignant melanoma. The DNA vaccine platform is safe, cost-effective and suitable for rapid and largescale manufacture. The team believe that the combined T cell and antibody approach will give more potent and long-lasting responses, ultimately leading to better protection.

The novel DNA vaccine will target two SARS-CoV-2 proteins in an effort to block both the virus itself and remove any infected cells. The nucleocapsid (N) protein, which makes up the bulk of the virus particle, and also the spike (S) protein, which enables the virus to gain entry into a cell.

Any surface protein, such as S, is the natural target for virus-killing antibodies, which prevent the virus from entering the cell.

As N protein is expressed inside infected cells, it is hoped that the N protein component of the vaccine will stimulate immune cells to recognise and kill virus-infected cells. The N protein is highly conserved amongst coronaviruses; therefore, this new vaccine has the potential to generate protection not only against SARS-CoV-2, but also against new coronaviruses that may arise in the future.

Vaccine-induced immunity to SARS-CoV-2 will be tested in samples from vaccinated people using tools developed at the University of Nottingham.

The project will be led by Professor Lindy Durrant, Chief Scientific Officer Scancell, and Professor of Cancer Immunotherapy at the University of Nottingham. Professor Durrant will work in collaboration with Professor Jonathan Ball, Dr James Dixon, Professor Janet Daly, Dr Chris Coleman and other colleagues in the Centre for Global Virus Infections and the new Biodiscovery Institute at the University of Nottingham, and alongside Professor Graham Pockley at the John van Geest Cancer Research Centre at Nottingham Trent University.

Professor Durrant, said: “T cells, and particularly high avidity T cells, are becoming increasingly recognised as an important factor in vaccine design for inducing long-term immunity against SARS CoV-2. Patients who had recovered from the original 2003 SARS infection have measurable T cell responses many years following recovery. We have been able to translate our ability to stimulate high avidity T cells to treat melanoma into a vaccine that can potentially provide an effective and durable immune response to COVID-19.”

‘Creating an effective immunity against COVID-19 requires the strongest antibody and T cell responses. Both strong molecular design and effective vaccine delivery is vital for success. We have a simple platform that can be used to effectively package and deliver the vaccine DNA with peptide nanoparticles. We aim to demonstrate safe, efficient and scalable formulation to provide the millions-billions of dosages needed to combat this global pandemic.”

Professor Pockley at Nottingham Trent University, said: “Nottingham Trent University and the John van Geest Cancer Research Centre are delighted to support Scancell’s endeavours to develop an effective vaccine for COVID-19. This exciting research programme highlights the capabilities and skills that are available in Nottingham and the value of collaborative working, not only between Universities, but also with commercial partners.”

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