Neutralization serotyping of BK polyomavirus infection in kidney transplant recipients

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.