The CDVAX proposal addresses a bacterial nosocomial pathogen, Clostridium difficile, of significant importance to Europe for four clear reasons:
- The bacterium carries multiple drug resistance that has been shown to transfer from strain to strain and from animals to humans
- Control of the disease in humans requires an extensive regimen of antibiotics
- The disease produces four-times as many mortalities as MRSA and is the leading hospital-acquired infection
- There is currently no marketed vaccine, or development stage vaccine able to prevent both primary infection and relapse
Current vaccine strategies under development are based on injection of bacterial toxoids, a classical systemic approach. While some efficacy is seen it is now accepted that to effectively vaccinate against C. difficile infection (CDI) the vaccine must confer the induction of mucosal antibodies at the site of infection and induce an immune response able to decolonise C. difficile from the gastrointestinal (GI) tract. Decolonisation is necessary to prevent recurrence of the disease, i.e., clinical relapse, which is the salient characteristic of nosocomial CDI. Other current therapeutic strategies do not address mucosal immunity or protection against relapse. The CDVAX consortium proposes to develop an orally delivered mucosal vaccine using antigens that have already been shown to protect animals challenged with C. difficile (i.e., primary infection and relapse), up to and including a first-in-man clinical study.
The consortium’s vaccine is termed CDVAX and uses bacterial spores for antigen delivery. It carries IP protection and the lead participant, Royal Holloway, University of London (RHUL) both owns the IP and will sponsor the clinical trial. In addition, four SMEs will work in partnership with RHUL, from France, Belgium and Germany.
The 36-month project will:
- optimise the vaccine for human studies,
- develop analytical tools to characterise the vaccine,
- produce GMP-compliant clinical batches,
- carry out regulatory and GLP-compliant toxicology studies and
- evaluate safety and immunogenicity using in a phase I, double blind, clinical trial.
The proposal is highly innovative using a novel oral delivery platform. The impact of this proposal is therefore significant both in terms of resolving a clear unmet clinical need and in developing oral vaccine expertise within European academic groups and SMEs. The outcome of this project will be the primary evaluation of an oral vaccine to CDI.