Scancell Holdings plc – Written evidence (COV0003)

Scancell Holdings plc is a UK based immunotherapy company with expertise in the development of cancer vaccines. As the COVID-19 pandemic has unfolded, Scancell has been evaluating how it can best contribute its expertise in immunology and drug development to help in the global response.

Currently, there are no approved coronavirus vaccines, so one that prevents infection would be of major benefit in controlling the current pandemic. It would also provide a prototype to prevent infection from any new emerging viruses. The vaccine needs to be safe, effective and scalable.

COVID-19 enters cells via its ‘spike’ or S protein binding to the ACE2 receptor. The need is therefore to stimulate neutralising antibodies (VNAbs) to the S-protein to prevent viral entry and to generate potent memory T cells to ensure clearance of virally infected cells.

Several COVID-19 vaccines are currently in development, including chimpanzee adenovirus, pox virus, RNA, DNA, protein and peptide vaccines. Most of these COVID-19 vaccines predominantly target the S protein and stimulate VNAbs but they do not focus on stimulating high avidity T cell responses; as a result it remains to be determined if they stimulate durable memory responses.

Targeting of dendritic cells is vital to stimulate high avidity T cells. Hence, we have designed a DNA vaccine that encodes two viral antigens, the nucleocapsid protein, or N-protein, and also the receptor binding domain of the S-protein. This results in direct targeting of dendritic cells to induce potent memory CD4 and CD8 T-cell responses to N-protein plus high titre VNAbs against the S-protein. This in turn can result in durable humoral and cellular immunity providing a blueprint for response upon subsequent viral challenge.

The vaccine is injected as a small circle of genetic information known as a DNA plasmid (pDNA). The pDNA contains the instructions to make two of the Covid-19 proteins. One of them is the nucleoprotein (N) (shown in pink) from inside the virus and the other is part of the outer Spike (S) protein (shown in purple). The N protein has been modified to direct it to dendritic cells and induce strong T cell responses. The vaccine will also produce a fragment of the S protein that helps the virus get into cells (the receptor-binding domain or RBD). The body’s immune system will then generate neutralising antibodies against the S protein so that the virus is unable to get into cells and infect them.

DNA vaccines are simple and fast to manufacture compared to other vaccine approaches but they require specialist delivery devices such as electroporation to ensure cellular transfection. To overcome this we have developed a simple non-toxic peptide delivery system which is as effective as electroporation and superior to lipid-based delivery systems.

In summary, our research will study whether the induction of VNAbs and T cells against the S protein combined with potent T cell responses against the N protein stimulate durable memory responses and achieve the goals set for an effective and long lasting vaccine. As the N protein is highly conserved amongst coronaviruses it also possible this vaccine may also confer protection against new emerging viruses.

14 May 2020