Roadmap for the development of candidate vaccines for FMD

What are we trying to achieve and why? What is the problem we are trying to solve?

Virus-like particles (VLPs) are non-replicating, non-pathogenic particles that have structural characteristics and antigenicity similar to the parental virus. The structural components of some VLPs have also proven amenable to the insertion or fusion of foreign antigenic sequences, allowing the production of chimeric VLPs exposing the foreign antigen on their surface.
The identification of suitable antigens and VLP expression system to develop a cross protective/multivalent species-specific subunit/peptide vaccine.

What are the scientific and technological challenges (knowledge gaps needing to be addressed)?

• Address cellular toxicity of FMDV 3C protein, leading to low/variable yields of capsid (partially addressed already)
• Manufacture mammalian cell culture systems
• Small size of vaccine antigens that can be incorporated into vaccine
• Define effects on non-humoral aspects of the immune response
• Reduce production costs

What approaches could/should be taken to address the research question?

• Establishing that there isn’t interference between the various antigens
• Monitoring the immune response following immunisation with the various combinations of candidate immunogens
• Challenge experiments with the various vaccine candidates
• If a multivalent vaccine isn’t possible then strain specific vaccines based on recognised antigen combinations will be needed
• Use of a VLP expression system to develop a cross protective/multivalent species-specific subunit vaccine
• Production of virus-like particles containing all the desired surface proteins

What else needs to be done before we can solve this need?

• Identify a combination of antigens that would generate protective responses or a common single antigen to which immune responses are normally suppressed
• Identify the most suitable VLP expression system
• The availability of a standardised challenge model

Existing knowledge including successes and failures

This platform is still in the Discovery phase. The majority of the VLP experimental FMD vaccines constructed to date have not been tested for efficacy in cattle or swine, and those that have been tested have shown only partial protection. Below some examples:

• Hepatitis B virus core particles, self-assemble into capsid particles and are extremely immunogenic, but formation of VLPs can be restricted by size and structure of heterologous antigens.
• Yeast-derived VLP experimental vaccines co-expressing either recombinant bovine IFN, IL-18 or HSP-70 and VLP P1 constructs has been shown to enhance SN and CMI responses in mice, but no livestock vaccine efficacy studies have been reported.
• Baculovirus- and E. coli-derived VLP experimental vaccines provide some protection against clinical disease in swine but fail to elicit strong protection against viral replication.
• The generation of VLP experimental vaccines using transgenic plants has shown some laboratory success but no vaccine candidate has been efficacy and safety tested in cattle or swine