Development of a Therapeutic mRNA Vaccine for COVID-19 using pHion's Delivery Technology

As infections with SARS-CoV-2 continue to rise with associated healthcare and economic implications, there is a race on to develop a vaccine to prevent the disease.

RNA vaccines are designed to encode the genetic sequences of antigens of a disease, in this instance SARS-CoV-2 and evoke an appropriate immune response.

There are several pipeline mRNA vaccines for SARS-CoV-2 that are designed to evoke a prophylactic response but as yet there is no therapeutic vaccine in development. To make a vaccine therapeutic, a particular type of immunity is required known as a CD8+ response.

Phion Therapeutics (Belfast SME) have a technology that when added to mRNA, creates a vaccine that produces a CD8+ response.

We get this response because we can deliver the vaccine into the correct cells (antigen presenting cells) using a cell penetrating peptide (RALA) as a delivery vehicle which is not recognised as foreign and bypasses the innate response.

RALA is designed to cross cellular membranes and fuse with endosomal membranes when the pH lowers which facilitates the release of the mRNA antigens into the cytosol without any associated toxicity. We are the only company to have this peptide to deliver the vaccine.

The vaccine itself is a genetic cargo (mRNA) designed to code for the antigens in a particular disease, in this instance multiple immunogenic proteins from SARS-CoV-2\.

RALA is adept at condensing all three mRNA into nanoparticles which are lyophilised and uniquely stable at room temperature without losing functionality.

Studies are designed to create a RALA/mRNA vaccine, validate baseline characteristics in humanised mice expressing the ACE-2 receptor, followed by determining the response in hamsters and then ferrets through outsourced challenge studies with SARS-CoV-2\. Finally, we will develop a regulatory framework to ensure progression to the clinic.

Outputs from this project are designed to provide definitive evidence of a robust prophylactic and therapeutic response using in vivo models.

With a comprehensive data package, by the end of this 18 month project we will have the candidate vaccine to progress to toxicology studies.

We believe that the RALA/mRNA technology marks the advent of a new generation of therapeutic vaccines that could clear viral infections on a global scale.

Most importantly, this platform technology for therapeutic vaccination will be made readily available to other industries and academics across the UK. With validation of automated scalability by the Centre for Process Innovation, pHion is confident of the supply chain.