Title: A Synthetic Biology-driven, high throughput approach to vaccine design
Funder: Biotechnology and Biological Sciences Research Council

Abstract: Vaccination has a key role to play in the control of bacterial infections, particularly as the rising incidence of antibiotic resistant strains is now a serious public health problem. For example, Novartis recently obtained licensure for Bexsero, a new vaccine against serogroup B meningococcal meningitis. It is likely that this vaccine will be introduced into clinical use in the UK, but it will be very expensive and it still uses outer membrane vesicles- a technology which is more than 30 years old. Also, development time is very slow- Bexsero has taken more than 15 years to come to market. This proposal is based on a different approach, which promises to speed up vaccine development considerably, at the same time as dramatically reducing production costs. It is based on a simple adaptation of the use of virus-like particles (VLPs). VLPs have been in clinical for a considerable time, and they are known to be safe and effective. Prof Derrick has shown that a single VLP particle can be engineered to display multiple antigens, using a synthetic polycistronic mRNA coding for multiple copies of the human hepatitis core viral capsid protein (HBc), fused to heterologous antigens from Neisseria meningitidis (the causative agent of meningococcal meningitis). Preliminary data shows that the modified VLPs elicit a protective response in an animal model. This approach extends current VLP technology in a new direction, offering enormous potential for the display of multiple antigens on a single VLP produced from one process run, considerably reducing the cost of goods. Additionally, the Derrick Lab has demonstrated that HBc VLPs 'capture' the mRNA which codes for them when they are expressed in E. coli. This observation establishes the potential for the design of large libraries of HBc-antigen fusions which can be screened for specific characteristics, such as stability or binding against antisera from animals or human patients. This innovation would allow for rapid, cost effective selection of candidate vaccines with a high level of optimisation derived from a clinically acceptable scaffold. Applications of this technology extend well beyond meningitis vaccines: it could be applied in circumstances where rapid development of a vaccine against a new disease is needed- in Biodefence, for example. The objectives of this proposal are to engage the consultants, Ithaka, to assess the potential of these discoveries and report on possible pathways to commercial implementation. This will be achieved by: 1. Working closely with the Client, Prof Derrick and his research team, building on information and contacts already available, to develop an initial technology specification and unique selling proposition. 2. Perform a high level analysis (using secondary sources and in-house expertise only), to determine whether the technology specification addresses new opportunities and areas of unmet need in the target markets. 3. To review outputs from the high level analysis with the Client to create a non-confidential technology brief. 4. To develop a detailed analysis of the shortlisted applications using primary and secondary sources and including a competitor analysis, to identify genuine opportunities. The deliverables from this report will be: 1. A high level market overview of information from secondary sources; 2. An assessment of the opportunities for the technology and competitive advantage(s); 3. More detailed analysis including feedback on the potential market opportunity from primary research with industry gatekeepers; 4. A summary of barriers to exploitation and conclusions regarding the potential commercial opportunity; 5. Identification of the data package necessary for a novel bacterial vaccine technology that would allow partnering opportunities with industry, and/or create an investable proposition for a start-up company, and the technical milestones that require to be achieved in any further research to achieve this.


Research activity codes: 3.4 VACCINES
Health categories: INFECTION