The Wellcome Trust has awarded £1.3M to the IAH and collaborators to investigate the translation of fundamental research into novel ways of producing better foot-and-mouth disease virus (FMDV) vaccines at a commercial level. IAH is collaborating with the Department of Structural Biology (University of Oxford), Intervet-Schering Plough Animal Health (Intervet-SPAH, Netherlands), ARC-Onderstepoort Veterinary Institute (South Africa), and the Plum Island Animal Disease Center (USA). The partnership is led by Dr Bryan Charleston of IAH.
Many types of FMD vaccines have poor stability. The virus particles disintegrate with time, especially if not kept cold, which is difficult in many countries where FMD vaccines are frequently required. Since it is only intact particles that induce protection, the result is poor immunity that is short-lived; re-vaccination is required. In this study, stabilizing mutations will be identified, in conjunction with the University of Oxford, and then introduced into the genome of FMDV of two serotypes, type 0 and SAT2, for which infectious clones are available within IAH and Onderstepoort, respectively. (FMDV infectious clones are DNA copies of the complete RNA genome of strains of FMDV. The DNA can be manipulated by standard molecular biology techniques, followed by production of FMDV RNA from which new FMDV particles are produced.)
Another drawback of producing FMDV on a scale large enough for vaccine manufacture - the poor growth of field strains in commercially-used cell cultures - will also be addressed. Plum island have an infectious clone of a strain of type A FMDV that grows well in cell culture, as it attaches well - unlike field strains - to heparin sulphate molecules at the surface of the cells. Genes encoding the proteins essential for the induction of protective immunity against other type A and SAT2 strains will be introduced into the genome of the cell culture-adapted virus by genetic manipulation. It is hoped that the resultant viruses will have the desired protection-inducing properties coupled with being able to grow well under commercial conditions.
Vaccine manufacturer Intervet-SPAH will do pilot studies on the growth of the modified FMDVs, and test the immunity induced by them.
This work has been developed in collaboration with the Global Foot-and-Mouth Disease Research Alliance (GFRA), which is committed to increasing our fundamental knowledge of foot-and-mouth disease (FMD), and to use that knowledge to develop new tools to assist the control and eventual eradication of the disease.
IAH has a major programme of research on FMDV, aimed not only at the production of better vaccines, but also of more rapid diagnostics, and an understanding how the disease spreads and persists. The IAH is also the FMD Reference Laboratory on behalf of Defra, the Food and Agriculture Organisation, and the World Organisation for Animal Health (OIE).