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 method of treating or inhibiting BK polyomavirus-associated nephropathy or BK polyomavirus-associated hemorrhagic cystitis in a subject, comprising administering to a subject in need of treatment for or inhibition of BK polyomavirus-associated nephropathy or BK polyomavirus-associated hemorrhagic cystitis a therapeutically effective amount of at least one isolated BKV serotype IV (BKV-IV) capsid polypeptide or a nucleic acid encoding the at least one BKV-IV capsid polypeptide, thereby treating or inhibiting the BK polyomavirus-associated nephropathy or the BK polyomavirus-associated hemorrhagic cystitis. 
     
     
         2 . The method of  claim 1 , further comprising administering to the subject a therapeutically effective amount of:
 at least one isolated BKV serotype I (BKV-I) capsid polypeptide or a nucleic acid encoding the at least one BKV-I capsid polypeptide;   at least one isolated BKV serotype II (BKV-II) capsid polypeptide or a nucleic acid encoding the at least one BKV-II capsid polypeptide;   at least one isolated BKV serotype III (BKV-III) capsid polypeptide or a nucleic acid encoding the at least one BKV-III capsid polypeptide;   at least one isolated JC polyomavirus capsid polypeptide or a nucleic acid encoding the at least one JC polyomavirus capsid polypeptide; or   a combination of two or more thereof.   
     
     
         3 . The method of  claim 1 , further comprising administering an adjuvant to the subject. 
     
     
         4 . The method of  claim 1 , wherein the subject is an immunocompromised subject or a subject who has been treated with or is a candidate for treatment with an immunosuppressant. 
     
     
         5 . The method of  claim 1 , wherein the subject is a subject who has received or is a candidate for an organ transplant. 
     
     
         6 . The method of  claim 5 , wherein the subject has received or is a candidate for a kidney transplant or a bone marrow transplant. 
     
     
         7 . The method of  claim 5 , wherein the subject is a candidate for an organ transplant and the therapeutically effective amount of the at least one BKV-IV capsid polypeptide or nucleic acid encoding the at least one BKV-IV capsid polypeptide is administered to the subject a sufficient time prior to the organ transplant to produce an immune response in the subject. 
     
     
         8 . The method of  claim 1 , wherein the subject does not have BKV-IV neutralizing antibodies. 
     
     
         9 . The method of  claim 1 , wherein the subject is a subject in need of treatment for or inhibition of BK polyomavirus-associated nephropathy. 
     
     
         10 . The method of  claim 9 , further comprising selecting the subject in need of treatment for or inhibition of BK polyomavirus-associated nephropathy.