Theranostics 2017; 7(6):1705-1718. doi:10.7150/thno.18301

Research Paper

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

Michael Schmitt1, 2✉, Anita Schmitt1, Markus Wiesneth3, Angela Hückelhoven1, Zeguang Wu4, Jürgen Kuball5, Lei Wang1, Peter Schauwecker3, Susanne Hofmann1, 6, Marlies Götz6, Birgit Michels1, Birgit Maccari3, Patrick Wuchter1, Volker Eckstein1, Thomas Mertens4, Paul Schnitzler7, Hartmut Döhner6, Anthony D. Ho1, 2, Donald W. Bunjes6, Peter Dreger1, Hubert Schrezenmeier3, Jochen Greiner6, 8

1. Dept. of Internal Medicine V, Heidelberg University Hospital, 69120 Heidelberg, Germany;
2. German Cancer Consortium/Deutsches Konsortium für Translationale Krebsforschung (DKTK), 69120 Heidelberg, Germany;
3. Institute of Clinical Transfusion Medicine and Immunogenetics Ulm, German Red Cross Blood Transfusion Service Baden-Württemberg-Hessen and Institute of Transfusion Medicine, University of Ulm, 89081 Ulm, Germany;
4. Institute of Virology, Ulm University Medical Center, 89081 Ulm, Germany;
5. Dept. of Hematology & Laboratory of Translational Immunology, University Medical Center, 3584 CX Utrecht, Netherlands;
6. Dept. of Internal Medicine III, University of Ulm, 89081 Ulm, Germany;
7. Dept. of Virology, University of Heidelberg, 69120 Heidelberg, Germany;
8. Dept. of Internal Medicine, Diakonie-Hospital Stuttgart, 70176 Stuttgart, Germany.

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.

Keywords: CMVpp65, CMV

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How to cite this article:
Schmitt M, Schmitt A, Wiesneth M, Hückelhoven A, Wu Z, Kuball J, Wang L, Schauwecker P, Hofmann S, Götz M, Michels B, Maccari B, Wuchter P, Eckstein V, Mertens T, Schnitzler P, Döhner H, Ho AD, Bunjes DW, Dreger P, Schrezenmeier H, Greiner J. 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. Theranostics 2017; 7(6):1705-1718. doi:10.7150/thno.18301. Available from http://www.thno.org/v07p1705.htm