Peptide vaccination against cytomegalovirus induces specific T cell response in responses in CMV seronegative end-stage renal disease patients

Introduction: Cytomegalovirus (CMV) reactivation occurs in seronegative patients after solid organ transplantation (SOT) particularly from seropositive donors and can be lethal. Generation of CMV-specific T cells helps to prevent CMV reactivation. Therefore, we initiated a clinical phase I CMVpp65 p...

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Main Authors: Sommerer, Claudia (Author) , Schmitt, Anita (Author) , Hückelhoven-Krauss, Angela (Author) , Giese, Thomas (Author) , Bruckner, Thomas (Author) , Wang, Lei (Author) , Schnitzler, Paul (Author) , Meuer, Stefan (Author) , Zeier, Martin (Author) , Schmitt, Michael (Author)
Format: Article (Journal)
Language:English
Published: 6 February 2021
In: Vaccines
Year: 2021, Volume: 9, Issue: 2, Pages: 1-15
ISSN:2076-393X
DOI:10.3390/vaccines9020133
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.3390/vaccines9020133
Verlag, lizenzpflichtig, Volltext: https://www.mdpi.com/2076-393X/9/2/133
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Author Notes:Claudia Sommerer, Anita Schmitt, Angela Hückelhoven-Krauss, Thomas Giese, Thomas Bruckner, Lei Wang, Paul Schnitzler, Stefan Meuer, Martin Zeier and Michael Schmitt
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Summary:Introduction: Cytomegalovirus (CMV) reactivation occurs in seronegative patients after solid organ transplantation (SOT) particularly from seropositive donors and can be lethal. Generation of CMV-specific T cells helps to prevent CMV reactivation. Therefore, we initiated a clinical phase I CMVpp65 peptide vaccination trial for seronegative end-stage renal disease patients waiting for kidney transplantation. Methods: The highly immunogenic nonamer peptide NLVPMVATV derived from CMV phosphoprotein 65(CMVpp65) in a water-in-oil emulsion (Montanide™) plus imiquimod (Aldara™) as an adjuvant was administered subcutaneously four times biweekly. Clinical course as well as immunological responses were monitored using IFN-γ ELISpot assays and flow cytometry for CMV-specific CD8+ T cells. Results: Peptide vaccination was well tolerated, and no drug-related serious adverse events were detected except for Grade I-II local skin reactions. Five of the 10 patients (50%) mounted any immune response (responders) and 40% of the patients presented CMV-specific CD8+ T cell responses elicited by these prophylactic vaccinations. No responders experienced CMV reactivation in the 18 months post-transplantation, while all non-responders reactivated. Conclusion: CMVpp65 peptide vaccination was safe, well tolerated, and clinically encouraging in seronegative end-stage renal disease patients waiting for kidney transplantation. Further studies with larger patient cohorts are planned.
Item Description:Gesehen am 09.09.2021
Physical Description:Online Resource
ISSN:2076-393X
DOI:10.3390/vaccines9020133