*Purpose: Definitive polyomavirus nephropathy (PyVN) affects kidney transplants and impacts allograft function and survival. Data suggest that neutralizing PyV strain specific antibodies can attenuate and possible even prevent disease. Here we report observations from the mouse on the protective role of anti-PyV antibodies.

*Methods: Six breeding mice had been exposed to murine PyV (MuPyV). They had developed a robust IgG response while lacking definitive PyVN and only showing minor qPCR evidence of intra organ MuPyV. Newborns of exposed breeders were split: group 1 (n=23) was injected at birth with MuPyV; group 2 (n=21) was not injected. Group 3 (n=24) was born to unexposed breeders and injected with MuPyV at birth. Tissue, plasma, and urine were analyzed at various time-points (0,1,2,3,6, and 10 weeks) by light microscopy, immunohistochemistry, qPCR, and MuPyV antibody titer testing. The nonparametric Wilcoxon Rank Sums test was used for P-value comparisons.

*Results: Newborns from exposed breeder has IgG titers between 160-640, no IgM, and only subclinical minor molecular evidence of intra organ MuPyV by qPCR. During 10 weeks of follow up, groups 1 and 2 both cleared MuPyV. By week 10, MuPyV was largely undetectable in the setting of significantly reduced IgG titers (0-40; no IgM). Prior to clearance, both groups displayed a mild transient increase in IgG titers (up to 2560; no IgM) at weeks 2 and 3. MuPyV clearance occurred earlier in group 2 with significantly lower qPCR reads in kidney noted on week 2 (P<0.03). There was no MuPyV induced organ injury. In contrast, group 3 showed persistently high intra organ qPCR reads starting post MuPyV injection on day 0 and lasting through week 10 (P<0.05 compared to groups 1/2). Histologically apparent viral tissue injury was first noticeable at week 1 and persisted thereafter. IgG and IgM levels remained undetectable until week 2, when they began to slowly rise. By week 10, IgG titers had risen significantly (up to 20480) while IgM titers had decreased to 0.

*Conclusions: Preexisting neutralizing antibodies protect from PyVN and facilitate clearance of subclinical MuPyV. In contrast, establishing MuPyV induced disease/injury is unaffected by neutralizing antibodies. This data can help with developing preventative treatment strategies in man.

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