BK polyomavirus (BKPyV) causes premature kidney transplant (KT) failure in 1-15% of patients. Since antivirals are lacking, most programs screen KT patients for BKPyV viremia and, if positive, reduce immunosuppression. We conducted a comprehensive study of BKPyV-specific immunity with focus on CD8 T-cells using a pool of 96 immunodominant 9mer epitopes (9mP) from the early viral gene region. Interferon-g EliSpot assays were compared with T-cell responses to 15mer pools and antibody levels at T0, T6, and T12 months posttransplant in prospectively cryopreserved cells and plasma of 96 KT patients (28 viremic; 68 non-viremic matched for transplantation period). Normalized BKPyV-specific IgG ELISAs revealed comparable seroprevalences at T0 between cases (89.3%) and controls (91.2%; p=0.8635), but cases had lower titers (p=0.022). 9mP and 15mP T-cell responses at T0 were not predictive of viremia, but, although onset and duration of viremia varied between patients, clearance was associated with stronger 9merP- than 15mP-responses both at T6 (p=0.044 vs. p=0.359) and T12 (p=0.048 vs. p=0.856). Antibodies increased at T6 and T12, but independent of viremia clearance. Following in vitro expansion and checkerboard analysis, 79 immunodominant 9mer epitopes were confirmed including 44 novel ones. Thus, BKPyV-specific T-cell responses to immunodominant 9mP are more sensitive than 15mer responses to guide immunosuppression reduction.The data of this study demonstrate for the first time that immunodominant 9mers can be used in the clinically relevant format of EliSpot assays to interrogate BKPyV-specific CD8 T-cells. Although the complexity of the 96 9mers is significantly lower than the 180 overlapping 15mer pools, the results indicate that targeting BKPyV-specific CD8 T-cell responses provide more sensitive functional information in patients having cleared BKPyV viremia.

CITATION INFORMATION: Hirsch H, Leboeuf C, Wilk S, Achermann R, Binet I, Golshayan D, Hadaya K, Hirzel C, Hoffmann M, Huynh-Do U, Koller M, Manuel O, Mueller N, Mueller T, Schaub S, Van Delden C, Weissbach F. BK Polyomavirus-Specific 9mer T-Cell Responses Predict Control of Viremia in Kidney Transplant Recipients: First Report from the Swiss Transplant Cohort Study. Am J Transplant. 2017;17 (suppl 3).

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