Synthetic Self-Assembling ADDomer Scaffold for Next-generation Biotherapeutics

Lead Research Organisation: University of Bristol
Department Name: Biochemistry

Abstract

In this project, we will use ADDomer, a versatile, designer antigen-presenting platform we developed. ADDomer originates from a single component of Adenovirus, the penton base protein. Engineered penton base proteins spontaneously form exceptionally stable synthetic virus-like particles in vitro, which are highly soluble and safe as they contain no genetic material. This innovative ADDomer scaffold is uniquely suited to display on a single particle hundreds of pathogenic epitopes and protein domains which are inserted into flexible, variable loops present on the ADDomer surface. In the project here proposed, we will combine expertise in synthetic biology and biodesign with protein engineering and cryo-electron microscopy to achieve a step-change in the potency of the ADDomer technology and create a uniquely powerful ADDoer-based vaccine prototype to combat coronavirus inculding SARS-CoV-2. Moreover, we will establish a versatile platform to enable rapid adaptation if new and currently unknown coronavirus threats arise (SARS-CoV-X). For translation to market, we will work with our industrial partner Imophoron Ltd, an award-winning Bristol start-up developing ADDomer as a next-generation vaccine platform technology. Building on this powerful synergy, we will utilize a range of biochemical, biophysical, engineering and marketing approaches to design, create, characterize, produce and roll-out highly effective next-generation ADDomer-based therapeutics to combat human infectious disease.

Publications

10 25 50

Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/T008741/1 01/10/2020 30/09/2028
2429411 Studentship BB/T008741/1 01/10/2020 30/09/2024 Charlotte Fletcher
 
Description A vaccine has been developed for Respiratory Syncytial Virus (RSV) using the ADDomer platform. The vaccine has been tested in a proof-of-concept animal study in a mouse model with promising results.
Exploitation Route The ADDomer RSV vaccine can be taken forward into further pre-clinical studies (challenge, toxicology etc) and clinical trials by Imophoron.
Sectors Pharmaceuticals and Medical Biotechnology

 
Description Imophoron Ltd 
Organisation Imophoron Ltd
Country United Kingdom 
Sector Private 
PI Contribution Design, production and biochemical and biophysical analysis of ADDomer RSV vaccine candidate
Collaborator Contribution Funding of proof-of-concept animal study (Balb/c mice) for ADDomer RSV vaccine candidate (at Charles River Laboratories). Opportunity to learn and perform immunology techniques
Impact An ADDomer RSV vaccine candidate with promising results in its proof-of-concept study
Start Year 2022
 
Title ADDomer RSV Vaccine 
Description ADDomer vaccine for RSV. Proof-of-concept study (in Balb/c mice) completed January 2023 with data analysis underway. This award (PhD studentship for Charlotte Fletcher) funded vaccine design and production of small research batches. Imophoron Ltd (PhD supervisor's start-up company) funded the animal study (performed by Charles River Laboratories, Portishead) 
Type Therapeutic Intervention - Vaccines
Current Stage Of Development Initial development
Year Development Stage Completed 2023
Development Status Under active development/distribution
Impact No vaccines for RSV are approved for use in humans currently so the development of an ADDomer RSV vaccine could potentially address an unmet need. 
 
Description Presented - UK Pediatric Vaccination Group (UKPVG) Meeting, December 2022 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Gave a 20 minute presentation describing the ADDomer platform to a large group of clinicians, epidemiologists and researchers. Described the background, production methods, and pre-clinical data from the ADDomer COVID-19 vaccine, along with preliminary data for my RSV vaccine.
Year(s) Of Engagement Activity 2022