title: Neutralization serotyping of BK polyomavirus infection in kidney transplant recipients.
abstract: BK polyomavirus (BKV or BKPyV) associated nephropathy affects up to 10% of kidney transplant recipients (KTRs). BKV isolates are categorized into four genotypes. It is currently unclear whether the four genotypes are also serotypes. To address this issue, we developed high-throughput serological assays based on antibody-mediated neutralization of BKV genotype I and IV reporter vectors (pseudoviruses). Neutralization-based testing of sera from mice immunized with BKV-I or BKV-IV virus-like particles (VLPs) or sera from naturally infected human subjects revealed that BKV-I specific serum antibodies are poorly neutralizing against BKV-IV and vice versa. The fact that BKV-I and BKV-IV are distinct serotypes was less evident in traditional VLP-based ELISAs. BKV-I and BKV-IV neutralization assays were used to examine BKV type-specific neutralizing antibody responses in KTRs at various time points after transplantation. At study entry, sera from 5% and 49% of KTRs showed no detectable neutralizing activity for BKV-I or BKV-IV neutralization, respectively. By one year after transplantation, all KTRs were neutralization seropositive for BKV-I, and 43% of the initially BKV-IV seronegative subjects showed evidence of acute seroconversion for BKV-IV neutralization. The results suggest a model in which BKV-IV-specific seroconversion reflects a de novo BKV-IV infection in KTRs who initially lack protective antibody responses capable of neutralizing genotype IV BKVs. If this model is correct, it suggests that pre-vaccinating prospective KTRs with a multivalent VLP-based vaccine against all BKV serotypes, or administration of BKV-neutralizing antibodies, might offer protection against graft loss or dysfunction due to BKV associated nephropathy.
authors.affiliation: Laboratory of Cellular Oncology, National Cancer Institute, Bethesda, Maryland, United States of America.
authors.forename: Diana V
authors.initials: DV
authors.lastname: Pastrana
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Brennan
authors.forename: Nicolas
authors.initials: N
authors.lastname: Cuburu
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Storch
authors.forename: Raphael P
authors.initials: RP
authors.lastname: Viscidi
authors.forename: Parmjeet S
authors.initials: PS
authors.lastname: Randhawa
authors.forename: Christopher B
authors.initials: CB
authors.lastname: Buck
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology* / Q000494:pharmacology; D000914:Antibodies, Viral; D001739:BK Virus / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007674:Kidney Diseases / Q000276:immunology / Q000517:prevention & control*; D016030:Kidney Transplantation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D027601:Polyomavirus Infections / Q000097:blood / Q000276:immunology / Q000517:prevention & control*; D013997:Time Factors; D014611:Vaccination / Q000379:methods; D014765:Viral Vaccines / Q000276:immunology / Q000494:pharmacology
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D014765:Viral Vaccines