Peptide vaccination in the presence of adjuvants in patients after hematopoietic stem cell transplantation with CD4+ T cell reconstitution elicits consistent CD8+ T cell responses

• Verfasst von: Schmitt, Michael [VerfasserIn]
• Verfasst von: Schmitt, Anita [VerfasserIn]
• Verfasst von: Hückelhoven-Krauss, Angela [VerfasserIn]
• Verfasst von: Wang, Lei [VerfasserIn]
• Verfasst von: Hofmann, Susanne [VerfasserIn]
• Verfasst von: Michels, Birgit [VerfasserIn]
• Verfasst von: Wuchter, Patrick [VerfasserIn]
• Verfasst von: Eckstein, Volker [VerfasserIn]
• Verfasst von: Schnitzler, Paul [VerfasserIn]
• Verfasst von: Ho, Anthony Dick [VerfasserIn]
• Verfasst von: Dreger, Peter [VerfasserIn]
• Titel: Peptide vaccination in the presence of adjuvants in patients after hematopoietic stem cell transplantation with CD4+ T cell reconstitution elicits consistent CD8+ T cell responses
• Verf.angabe: Michael Schmitt, Anita Schmitt, Markus Wiesneth, Angela Hückelhoven, Zeguang Wu, Jürgen Kuball, Lei Wang, Peter Schauwecker, Susanne Hofmann, Marlies Götz, Birgit Michels, Birgit Maccari, Patrick Wuchter, Volker Eckstein, Thomas Mertens, Paul Schnitzler, Hartmut Döhner, Anthony D. Ho, Donald W. Bunjes, Peter Dreger, Hubert Schrezenmeier, and Jochen Greiner
• Jahr: 2017
• Umfang: 14 S.
• Fussnoten: Published: 2017.04.10 ; Gesehen am 12.06.2018
• Titel Quelle: Enthalten in: Theranostics
• Ort Quelle: Wyoming, NSW : Ivyspring, 2011
• Jahr Quelle: 2017
• Band/Heft Quelle: 7(2017), 6, Seite 1705-1718
• ISSN Quelle: 1838-7640
• DOI: doi:10.7150/thno.18301
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1576281205

Abstract

Rationale: Patients receiving an allogeneic stem cell graft from cytomegalovirus (CMV) seronegative donors are particularly prone to CMV reactivation with a high risk of disease and mortality. Therefore we developed and manufactured a novel vaccine and initiated a clinical phase I trial with a CMV phosphoprotein 65 (CMVpp65)-derived peptide. Methods: Ten patients after allogeneic stem cell transplantation received four vaccinations at a biweekly interval. All patients were monitored for CMVpp65 antigenemia. Flow cytometry for CMV-specific CD8+ and γδ T cells as well as neutralizing anti-CMV antibodies were correlated to clinical parameters.Results: The vaccination was well tolerated. Seven of nine patients cleared CMVpp65 antigenemia after four vaccinations and are still free from antigenemia to this day. Two patients with CMV reactivation showed persisting CMV antigenemia. One patient received prophylactic vaccination and did not develop antigenemia. An increase of up to six-fold in frequency of both CMV-specific CD8+ T cells and/or Vδ2negative γδ T cells was detected. Titers of neutralizing antibodies increased up to the tenfold. Humoral and cellular immune responses correlated with clearance of CMV. Conclusion: In summary, CMVpp65 peptide vaccination for patients after allogeneic stem cell transplantation at high risk for CMV reactivation was safe, well tolerated and clinically encouraging. A study in solid-organ transplant patients is ongoing.