Peptide Vaccination Against Cytomegalovirus Induces Specific T Cell Response in Responses in CMV Seronegative End-Stage Renal Disease Patients

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: Claudia Sommerer, Anita Schmitt, Angela Hückelhoven-Krauss, Thomas Giese, Thomas Bruckner, Lei Wang, Paul Schnitzler, Stefan Meuer, Martin Zeier, Michael Schmitt
Format: Article
Language:English
Published: MDPI AG 2021-02-01
Series:Vaccines
Subjects:
cytomegalovirus (CMV)
CMV reactivation
phosphoprotein 65 (pp65) peptide vaccination
specific T cells
renal transplantation
Online Access:https://www.mdpi.com/2076-393X/9/2/133
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spelling doaj-52191f18891c48e392688c5183a91c072021-02-07T00:04:07ZengMDPI AGVaccines2076-393X2021-02-01913313310.3390/vaccines9020133Peptide Vaccination Against Cytomegalovirus Induces Specific T Cell Response in Responses in CMV Seronegative End-Stage Renal Disease PatientsClaudia Sommerer0Anita Schmitt1Angela Hückelhoven-Krauss2Thomas Giese3Thomas Bruckner4Lei Wang5Paul Schnitzler6Stefan Meuer7Martin Zeier8Michael Schmitt9Department of Nephrology, University Hospital Heidelberg, University of Heidelberg, 69117 Heidelberg, GermanyDepartment of Internal Medicine V, University of Heidelberg, 69117 Heidelberg, GermanyDepartment of Internal Medicine V, University of Heidelberg, 69117 Heidelberg, GermanyGerman Center for Infection Research DZIF, Heidelberg, GermanyInstitute of Medical Biometry and Informatics, University of Heidelberg, 69117 Heidelberg, GermanyDepartment of Internal Medicine V, University of Heidelberg, 69117 Heidelberg, GermanyDepartment of Virology, University Hospital Heidelberg, University of Heidelberg, 69117 Heidelberg, GermanyGerman Center for Infection Research DZIF, Heidelberg, GermanyDepartment of Nephrology, University Hospital Heidelberg, University of Heidelberg, 69117 Heidelberg, GermanyDepartment of Internal Medicine V, University of Heidelberg, 69117 Heidelberg, GermanyIntroduction: 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<sup>+</sup> 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<sup>+</sup> 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.https://www.mdpi.com/2076-393X/9/2/133cytomegalovirus (CMV)CMV reactivationphosphoprotein 65 (pp65) peptide vaccinationspecific T cellsrenal transplantation
collection DOAJ
language English
format Article
sources DOAJ
author Claudia Sommerer
Anita Schmitt
Angela Hückelhoven-Krauss
Thomas Giese
Thomas Bruckner
Lei Wang
Paul Schnitzler
Stefan Meuer
Martin Zeier
Michael Schmitt
spellingShingle Claudia Sommerer
Anita Schmitt
Angela Hückelhoven-Krauss
Thomas Giese
Thomas Bruckner
Lei Wang
Paul Schnitzler
Stefan Meuer
Martin Zeier
Michael Schmitt
Peptide Vaccination Against Cytomegalovirus Induces Specific T Cell Response in Responses in CMV Seronegative End-Stage Renal Disease Patients
Vaccines
cytomegalovirus (CMV)
CMV reactivation
phosphoprotein 65 (pp65) peptide vaccination
specific T cells
renal transplantation
author_facet Claudia Sommerer
Anita Schmitt
Angela Hückelhoven-Krauss
Thomas Giese
Thomas Bruckner
Lei Wang
Paul Schnitzler
Stefan Meuer
Martin Zeier
Michael Schmitt
author_sort Claudia Sommerer
title Peptide Vaccination Against Cytomegalovirus Induces Specific T Cell Response in Responses in CMV Seronegative End-Stage Renal Disease Patients
title_short Peptide Vaccination Against Cytomegalovirus Induces Specific T Cell Response in Responses in CMV Seronegative End-Stage Renal Disease Patients
title_full Peptide Vaccination Against Cytomegalovirus Induces Specific T Cell Response in Responses in CMV Seronegative End-Stage Renal Disease Patients
title_fullStr Peptide Vaccination Against Cytomegalovirus Induces Specific T Cell Response in Responses in CMV Seronegative End-Stage Renal Disease Patients
title_full_unstemmed Peptide Vaccination Against Cytomegalovirus Induces Specific T Cell Response in Responses in CMV Seronegative End-Stage Renal Disease Patients
title_sort peptide vaccination against cytomegalovirus induces specific t cell response in responses in cmv seronegative end-stage renal disease patients
publisher MDPI AG
series Vaccines
issn 2076-393X
publishDate 2021-02-01
description 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<sup>+</sup> 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<sup>+</sup> 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.
topic cytomegalovirus (CMV)
CMV reactivation
phosphoprotein 65 (pp65) peptide vaccination
specific T cells
renal transplantation
url https://www.mdpi.com/2076-393X/9/2/133
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