Porcine reproductive and respiratory syndrome (PRRS) is the most important viral disease in pigs worldwide. Failure of vaccination and the emergence of highly virulent strains, the so-called High Fever Disease (HFD) PRRSV strains, cause huge economical losses to pig industry and is a big issue in animal welfare. HFD PRRSV strains of genotype II (American) emerged in 2006 in Asia. At present, the situation is there out of hand. These HFD PRRSV II strains pose a long distance threat to Europe. However, at the same time HFD PRRSV strains of type I (European, subtype 3 (Lena-like)) were also discovered in Eastern Europe (Belarus). This year, more virulent/pathogenic PRRSV I subtype 1 strains emerged in Western Europe, causing fever for one week and respiratory problems. Type I HFD PRRSV strains replicate to higher levels (x10-100) than the traditional PRRSV strains by infecting more subtypes of monocytic cells (use of new receptors), suppress heavily the antimicrobial defence and immune responses and cause respiratory problems and mortality. Vaccination against these strains with commercial attenuated and inactivated vaccines sometimes lead to an aggravation of the disease instead of protection. Type I HFD strains are menacing now the whole European pig industry. This brings HFD PRRS in the group of viral diseases that cannot be fully controlled by the available vaccines. Therefore, HFD PRRS should be prioritized in surveillance (diagnosis) and search for safe and efficacious vaccines. In the present project proposal, a group of five European PRRS experts that are already cooperating in a EU PRRS project (2009-2014) will join forces again to control HFD PRRS in Europe. By studying the pathogenesis, it will be examined what the mechanisms are of (i) the higher replication power of HFD PRRSV (target cells, new receptors), (ii) the immunosuppression and (iii) the immunity-dependent enhancement of virus replication. Based on the results new vaccines (inactivated/vector/attenuated) will be designed, developed and tested. In parallel, PRRS surveillance will be launched, in order to trace HFD PRRSV and to take the correct actions, whenever this virus causes a catastrophic epidemic in Western Europe.