Methods and compositions for inhibiting polyomavirus-associated pathology

Abstract

Disclosed herein are methods of eliciting an immune response against a polyomavirus (for example, BKV serotype I (BKV-I), BKV serotype II (BKV-II), BKV serotype III (BKV-III) and/or BKV serotype IV (BKV-IV)) and methods of treating or inhibiting polyomavirus-associated pathology (such as polyomavirus-associated nephropathy, BKV-associated hemorrhagic cystitis, or JC virus-associated progressive multifocal leukoencephalopathy; PML). Further disclosed are immunogenic compositions of use in the disclosed methods. Also disclosed are methods of selecting an organ transplant donor and/or recipient including detecting whether the prospective donor and/or recipient has BKV serotype-specific (such as BKV serotype IV-specific) neutralizing antibodies.

We claim: 
     
         1 . A multivalent BK polyomavirus (BKV) immunogenic composition comprising:
 a virus-like particle comprising at least one BKV serotype IV capsid polypeptide;   a virus-like particle comprising at least one BKV serotype I capsid polypeptide;   a pharmaceutically acceptable carrier; and   an adjuvant.   
     
     
         2 . The composition of  claim 1 , wherein the at least one BKV-IV capsid polypeptide comprises the amino acid sequence of any one of SEQ ID NOs: 4-6, 16, and 110-125 and the at least one isolated BKV-I capsid polypeptide comprises the amino acid sequence of any one of SEQ ID NOs: 1-3, 13-15, and 52-103. 
     
     
         3 . The composition of  claim 1 , further comprising:
 a virus-like particle comprising at least one BKV serotype II capsid polypeptide;   a virus-like particle comprising at least one BKV serotype III capsid polypeptide; or   a combination thereof.   
     
     
         4 . The composition of  claim 1 , wherein the at least one capsid polypeptide comprises VP1, VP2, VP3, or a combination of two or more thereof. 
     
     
         5 . The composition of  claim 1 , wherein the at least one BKV serotype IV capsid polypeptide comprises one or more of a BKV-IVb1 VP1 polypeptide and/or a BKV-IVc2 VP1 polypeptide. 
     
     
         6 . The composition of  claim 5 , wherein the BKV-IVb1 VP1 polypeptide is encoded by a nucleic acid molecule comprising the sequence of SEQ ID NO: 47 and/or the BKV-IVc2 VP1 polypeptide is encoded by a nucleic acid molecule comprising the sequence of SEQ ID NO: 27 or 39. 
     
     
         7 . The composition of  claim 1 , wherein the at least one BKV serotype I capsid polypeptide comprises one or more of a BKV-Ia VP1 polypeptide, a BKV-Ib1 VP1 polypeptide, a BKV-Ib2 VP1 polypeptide, and/or a BKV-Ic VP1 polypeptide. 
     
     
         8 . The composition of  claim 7 , wherein the BKV-Ia VP1 polypeptide is encoded by a nucleic acid molecule comprising the sequence of SEQ ID NO: 42, the BKV-Ib1 VP1 polypeptide is encoded by a nucleic acid molecule comprising the sequence of SEQ ID NO: 24; the BKV-Ib2 VP1 polypeptide is encoded by a nucleic acid molecule comprising the sequence of SEQ ID NO: 43; and/or the BKV-Ic VP1 polypeptide is encoded by a nucleic acid molecule comprising the sequence of SEQ ID NO: 44. 
     
     
         9 . The composition of  claim 1 , wherein the virus-like particle comprising at least one BKV-IV capsid polypeptide comprises a BKV-IV VP1 polypeptide, and the virus-like particle comprising at least one BKV-I capsid polypeptide comprises a BKV-Ia VP1 polypeptide and/or a BKV-Ib2 VP1 polypeptide. 
     
     
         10 . The composition of  claim 1 , further comprising a virus-like particle comprising at least one JC polyomavirus capsid polypeptide. 
     
     
         11 . A multivalent BK polyomavirus (BKV) immunogenic composition comprising:
 a virus-like particle comprising at least one BKV serotype IV VP1 polypeptide, wherein the at least one BKV serotype IV VP1 polypeptide is encoded by a nucleic acid molecule comprising the sequence of SEQ ID NO: 39 or SEQ ID NO: 47;   a virus-like particle comprising at least one BKV serotype I VP1polypeptide, wherein the at least one BKV serotype I VP1 polypeptide is encoded by a nucleic acid molecule comprising the sequence of one of SEQ ID NOs: 42-44; and   a pharmaceutically acceptable carrier.   
     
     
         12 . The composition of  claim 11 , wherein the at least one BKV-IV VP1 polypeptide comprises the amino acid sequence of SEQ ID NO: 4 or SEQ ID NO: 16 and/ot the at least one isolated BKV-I VP1 polypeptide comprises the amino acid sequence of any one of SEQ ID NOs: 1 and 13-15. 
     
     
         13 . The composition of  claim 11 , further comprising:
 a virus-like particle comprising at least one BKV serotype II capsid polypeptide;   a virus-like particle comprising at least one BKV serotype III capsid polypeptide; or   a combination thereof.   
     
     
         14 . The composition of  claim 11 , wherein the virus-like particle further comprises a VP2 polypeptide, a VP3 polypeptide, or a combination of two or more thereof. 
     
     
         15 . The composition of  claim 11 , wherein the at least one BKV serotype IV VP1 polypeptide comprises one or more of a BKV-IVb1 VP1 polypeptide and/or a BKV-IVc2 VP1 polypeptide. 
     
     
         16 . The composition of  claim 11 , wherein the at least one BKV serotype I VP1 polypeptide comprises one or more of a BKV-Ia VP1 polypeptide, a BKV-Ib1 VP1 polypeptide, a BKV-Ib2 VP1 polypeptide, and/or a BKV-Ic VP1 polypeptide. 
     
     
         17 . The composition of  claim 11 , wherein the virus-like particle comprising at least one BKV-IV VP1 polypeptide comprises a BKV-IV VP1 polypeptide, and the virus-like particle comprising at least one BKV-I VP1 polypeptide comprises a BKV-Ia VP1 polypeptide and/or a BKV-Ib2 VP1 polypeptide. 
     
     
         18 . The composition of  claim 11 , further comprising a virus-like particle comprising at least one JC polyomavirus capsid polypeptide. 
     
     
         19 . The composition of  claim 11 , further comprising an adjuvant.