Novel approaches to foot-and-mouth disease vaccine development.

The need for better foot-and-mouth disease (FMD) vaccines is not new, a report from the Research Commission on FMD, authored by F. Loeffler and P. Frosch in 1897, highlighted the need for developing a vaccine against FMD and qualified this as a devastating disease causing "severe economic damage to the country's agriculture" [1]. Inactivated antigen vaccines have been available since the early 1900s and have been instrumental in eradicating FMD from parts of the world and repressing clinical disease in others. However, these vaccines require using live virulent FMDV for manufacturing, fail to prevent infection resulting in the establishment of carrier animals, require multiple vaccination schedules (every six months) and have limited coverage to the specific serotype and in many cases subtype of FMDV. Therefore, FMD vaccinology continues to be a very active research field. Research-based novel vaccine approaches over the last decade have resulted in at least one novel molecular vaccine being licensed for emergency use in the US and multiple other vaccine approaches being actively pursued as alternatives to current vaccines. Here we will review and update the main research efforts on FMD vaccines, including subunit and peptide vaccines, DNA vaccines, empty capsid vaccines (directly delivered or vector delivered), novel inactivated antigen production platforms and live attenuated vaccines. Each of these approaches will be discussed in terms of their safety and efficacy characteristics, product transition feasibility as well as their applicability to global control and eradication efforts.