*Purpose: BKPyV persists as significant cause of premature kidney transplant failure. Current treatment is based on reducing immunosuppression to regain immune control over BKPyV replication [1, 2]. BKPyV-specific T cells have been shown to play a major role in this regard, whereby increasing cytotoxic CD8 T cells have been associated with clearance of BKPyV-DNAemia [3]. We aimed at characterising the role of antigen-presenting cells (APCs), CD4 T cells and adjuvants in boosting peptide-specific BKPyV-specific CD8+T cell responses in vitro.

*Methods: 25 BKPyV-Vp1-VLP IgG ELISA seropositive blood donors (BD) were HLA-typed using NGS sequencing. Cryopreserved PBMCs were differentiated into monocyte-derived dendritic cells (Mo-DCs) and monocyte-derived Langerhans cells (Mo-LCs). Mo-DCs and Mo-LCs were pulsed with overlapping 15mer peptide pools (15mP) covering the BKPyV large Tumor-antigen (LTag) and co-cultured with autologous T cells. Cells were re-stimulated either with 15mP or the 9mP containing 97 immunodominant 9mer epitopes [4]. BKPyV-specific T cell responses were measured using IFNy-ELISpot and FACS.

*Results: Mo-LCs induced higher overall BKPyV-specific CD4 T cell responses than Mo-DCs, whereas overall CD8 T cell responses were similar, with some exceptions (Figure 1A). BKPyV-specific CD8 T cell responses required CD4 T cell help, since selective CD4 T cell removal showed significant reductions in CD8 T cell IFNy-responses (Figure 1B). Using MF59-adjuvant, BKPyV-specific T cell responses were increased in 3 individuals among the 6 donors tested. Notably, HLA-B7 and HLA-B8 BD (n=2) showed higher CD8 T cell responses to the immunodominant 9m127 peptide in the presence of adjuvant [5].

*Conclusions: Our data indicate the peptide-dependent increase of CD8 T cells responses using rational combinations of peptides, APCs, CD4 T cells and adjuvant. The relevance for peptide-specific vaccines will be evaluated.

[1] Hirsch HH, Randhawa PS, AST-IDCOP (2019) Clin Transplant: e13528; [2] Kaur A et al (2019) Curr Opin Infect Dis 32: 575; [3] Leboeuf C et al (2017) Am J Transplant 17: 2591; [4] Cioni M et al (2016) Am J Transplant 16: 1193; [5] Wilhelm M et al (2019) Transplantation 103: e384;

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