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?

Identify the immunomodulatory factors/evasion mechanisms of FMDV

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

• Determine FMDV immune evasion mechanisms: is diversity a virulence factor?
• Identify the mechanisms of immunomodulation and the virus proteins responsible

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

• Studying the biological significance of the antagonistic events under physiological conditions of FMDV infection, preferably in primary cells from relevant target tissues of natural host species
• Generation of a range of knock-out viruses where the genes for various immunomodulatory factors or other stealth mechanisms have been removed and their use in experimental infections.

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

Host pathogen interaction

Existing knowledge including successes and failures

FMDV can evade innate immune responses through its ability to shut down cellular protein synthesis, including IFN type I, in susceptible epithelial cells. While earlier work identified roles for FMDV L(pro) and 3C(pro) in inhibiting the production of type I IFN, new data show that 3C(pro) can also impede signalling downstream of the type I IFN receptor. Recent research also identified distinct roles for the two forms of L(pro) that arise during viral replication, Lab(pro) and Lb(pro), with implications for our understanding of this protein as a molecular virulence factor