Arterivirus

Abstract

The present invention relates to replication-competent Arteriviruses having a decreased DUB/deISGylating activity due to a mutation in the PLP2 domain of the non-structural protein nsp2, to their use as a medicament, their use as a vaccine and in prophylaxis, to vaccines comprising such Arteriviruses and to Arteriviral PLP2-ubiquitin complexes.

1 - 20 . (canceled) 
     
     
         21 . A live attenuated vaccine comprising a replication-competent Arterivirus and a pharmaceutically acceptable carrier, wherein said Arterivirus comprises a decreased DUB/deISGylating activity due to a mutation in the PLP2 domain of the non-structural protein nsp2. 
     
     
         22 . The live attenuated vaccine of  claim 21 , wherein said Arterivirus comprises a mutation in at least 2 different consensus position regions selected from the group consisting of consensus position regions 296-297, 303-306, 309-319, 326-330 and 343-355 according to the EAV numbering as depicted in  FIG. 3 . 
     
     
         23 . The live attenuated vaccine of  claim 22 , wherein said Arterivirus comprises a mutation in at least 3 different consensus position regions. 
     
     
         24 . The live attenuated vaccine of  claim 21 , wherein said Arterivirus comprises a mutation at one or more of the consensus positions T312, I313 and I353 according to the EAV numbering as depicted in  FIG. 3 . 
     
     
         25 . The live attenuated vaccine of  claim 21 , wherein said Arterivirus is selected from the group of viruses consisting of Equine arteritis virus (EAV) and Porcine respiratory and reproductive syndrome virus (PRRSV). 
     
     
         26 . The live attenuated vaccine of  claim 21 , wherein said mutations in the PLP2 domain are located at consensus position regions 296-297, 303-306, 310-318, 327-329 or 343-354 according to the EAV numbering as depicted in  FIG. 3 . 
     
     
         27 . The live attenuated vaccine of  claim 26 , wherein said mutations in the PLP2 domain are located at consensus position regions 296-297, 303-306, 311-317, 328, 343-346, 347-348 or 350-353 according to the EAV numbering as depicted in  FIG. 3 . 
     
     
         28 . The live attenuated vaccine of  claim 27 , wherein said mutations in the PLP2 domain are at consensus positions T312, I313 or I353. 
     
     
         29 . The live attenuated vaccine of  claim 28 , wherein said Arterivirus is EAV and said mutations in the PLP2 domain are chosen from T312A, I313V, I353A, I353R, I353S, I353T or I353W. 
     
     
         30 . The live attenuated vaccine of  claim 24 , wherein said Arterivirus comprises at least 2 mutations, each of which contributes to a decreased DUB/deISGylating activity. 
     
     
         31 . The live attenuated vaccine of  claim 21 , wherein said vaccine comprises an additional immunogen of a virus or micro-organism pathogenic to the animal to be vaccinated, an antibody against said immunogen, or genetic information encoding an immunogen of said virus or micro-organism. 
     
     
         32 . The live attenuated vaccine of  claim 31 , wherein said the virus or micro-organism pathogenic to the animal to be vaccinated is selected from the group of  Brachyspira hyodysenteriae , African Swine Fever virus, Nipah virus, Porcine Circovirus, Porcine Torque Teno virus, Pseudorabies virus, Porcine influenza virus, Porcine Epidemic Diarrheal virus (PEDV), Foot and Mouth disease virus, Transmissible gastro-enteritis virus, Rotavirus,  Escherichia coli, Erysipelo rhusiopathiae, Bordetella bronchiseptica, Salmonella cholerasuis, Haemophilus parasuis, Pasteurella multocida, Streptococcus suis, Mycoplasma hyopneumoniae  and  Actinobacillus pleuropneumoniae.    
     
     
         33 . The live attenuated vaccine of  claim 31 , wherein said the virus or micro-organism pathogenic to the animal to be vaccinated is selected from the group consisting of Equine Influenza virus,  Clostridium tetani , Equine Herpesvirus 1 and Equine Herpesvirus 4. 
     
     
         34 . A method of making a replication-competent Arterivirus which has a decreased DUB/deISGylating activity due to a mutation in the PLP2 domain of the non-structural protein nsp2, comprising recombinantly introducing a mutation in the PLP2 domain of the non-structural protein nsp2. 
     
     
         35 . The method of  claim 34 , wherein said Arterivirus comprises a mutation in 2 different consensus position regions chosen from the group consisting of consensus position regions 296-297, 303-306, 309-319, 326-330 and 343-355 according to the EAV numbering as depicted in  FIG. 3 . 
     
     
         36 . The method of  claim 34 , wherein said Arterivirus comprises a mutation at one or more of the consensus positions T312, I313 and I353 according to the EAV numbering as depicted in  FIG. 3 . 
     
     
         37 . A replication competent Arterivirus obtained by the method of  claim 34 . 
     
     
         38 . A replication-competent Arterivirus, characterized in that said virus has a decreased DUB/deISGylating activity due to a mutation in the PLP2 domain of the non-structural protein nsp2.