Please use this identifier to cite or link to this item: https://observatorio.fm.usp.br/handle/OPI/34033
Title: Generation of Zika virus - specific T cells from seropositive and virus-naive donors for potential use as an autologous or ""off-the-shelf"" immunotherapeutic
Authors: HANAJIRI, RyoSANI, Gelina M.HANLEY, Patrick J.SILVEIRA, Cassia G.KALLAS, Esper G.KELLER, Michael D.BOLLARD, Catherine M.
Citation: CYTOTHERAPY, v.21, n.8, p.840-855, 2019
Abstract: Background: Zika virus (ZIKV) infection can cause severe birth defects in newborns with no effective currently available treatment. Adoptive transfer of virus-specific T cells has proven to be safe and effective for the prevention or treatment of many viral infections, and could represent a novel treatment approach for patients with ZIKV infection. However, extending this strategy to the ZIKV setting has been hampered by limited data on immunogenic T-cell antigens within ZIKV. Hence, we have generated ZIKV-specific T cells and characterized the cellular immune responses against ZIKV antigens. Methods: T-cell products were generated from peripheral blood of ZIKV-exposed donors, ZIKV-naive adult donors and umbilical cord blood by stimulation with pentadecamer (15mer) overlapping peptide libraries spanning four ZIKV polyproteins (C, M, E and NS1) using a Good Manufacturing Practice compliant protocol. Results: We successfully generated T cells targeting ZIKV antigens with clinically relevant numbers. The ex vivo-expanded T cells comprised both CD4(+) and CD8(+) T cells that were able to produce Th1-polarized effector cytokines and kill ZIKV-infected HLA-matched monocytes, confirming functionality of this unique T-cell product as a potential ""off-the-shelf"" therapeutic. Epitope mapping using peptide arrays identified several novel HLA class I and class II restricted epitopes within NS1 antigen, which is essential for viral replication and immune evasion. Discussion: Our findings demonstrate that it is feasible to generate potent ZIKV-specific T cells from a variety of cell sources including virus naive donors for future clinical use in an ""off-the-shelf"" setting.
Appears in Collections:Artigos e Materiais de Revistas Científicas - FM/MIP
Artigos e Materiais de Revistas Científicas - HC/ICHC
Artigos e Materiais de Revistas Científicas - LIM/60

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