Gastrointestinal infections are common in new-born animals in intensive animal husbandry, and pose a serious economic threat. While antibacterial agents have been very effective, antivirals have met with ! limited success. This project proposes to use a procedure known as intracellular immunization, in'which neonatal pigs will be inoculated with defective (non-infectious) viral genomes in order to prevent enteric infections. These defective genomes are small (<=10 kb) and have the unique ability of interfering at the molecular level with (i.e. inhibiting) the multiplication of homologous infectious virus, and are known as defective interfering (DI) genomes. In vivo they need be p resent only in a sufficient number of cells to reduce infection and hence allow the host's defence mechanisms to overcome the virus.
Intracellular immunization will be specifically tarqeted to tissues normally infected by the viral pathogen, using virus-like particles (VLPS) with envelope proteins that confer the required cell tropism.
Benefit will be mediated by two complementary mechanisms: (1) direct interference with virus multiplication in the cell which is effective immediately after administration and (2) induction of a conventional protective immune response which is effective after a few days, in a; manner analogous to human neonates who can be successively immunized by gut infection with oral poliovirus vaccine. Intracellular immunization will be developed for viruses of neonatal pigs . transmissible gast-; enteritis viru- (TGEV) and porcine epidemic diarrhoea virus (PEDV). Inj 1994 these viruses were major contributors to enteric and respiratory ! infections which cost the EU about 766 million ECU, (51,*' of an industry worth 15000 million ECU, and comparable to that of North America). In addition there is a major social impact as these losses are borne by small farmers rather than powerful industrial concerns. VLPs will be developed that target cloned TGEV DI RNA to pig enteric tract epithelial cells in culture. The final goal is the successful oral administration of this material to combat TGEV-induced disease in neonatal pigs. Successful development requires a transnational combination of the complementary expertises of four research groups and a company to (1) understand the molecular basis of intracellular immunity induced by DI virus genomes; (2) design VLPs to target the interfering molecules to tissues infected by the pathogen. (3) express interference with TGEV replication that is active in porcine gut! epithelial cells and (4) evaluate protection in neonatal pigs against TGEV and PEDV. This technology will have many applications as a novel, practical, effective, and safe means for controlling and preventing virus diseases of live-stock in the EU. North America and world-wide.
Funding SchemeCSC - Cost-sharing contracts
17813 Vall De Bianya, Gerona
2300 RC Leiden