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Heterologous prime-boost vaccination protects against EBV antigen-expressing lymphomas.

  • Rühl J Viral Immunobiology, Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
  • Citterio C Viral Immunobiology, Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
  • Engelmann C Viral Immunobiology, Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
  • Haigh T Cancer Immunology and Immunotherapy Centre, University of Birmingham, Birmingham, United Kingdom.
  • Dzionek A Miltenyi Biotec GmbH, Bergisch Gladbach, Germany.
  • Dreyer J Institute for Pathology, Unfallkrankenhaus Berlin, Berlin, Germany.
  • Khanna R QIMR Berghofer Centre for Immunotherapy and Vaccine Development and Tumour Immunology Laboratory, Department of Immunology, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
  • Taylor GS Cancer Immunology and Immunotherapy Centre, University of Birmingham, Birmingham, United Kingdom.
  • Wilson JB College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom.
  • Leung CS University of Oxford, Nuffield Department of Medicine, Ludwig Institute for Cancer Research, Oxford, United Kingdom.
  • Münz C Viral Immunobiology, Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland.
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  • 2019-05-02
Published in:
  • The Journal of clinical investigation. - 2019
Immunology
Lymphomas
Animals
CD4-Positive T-Lymphocytes
CD8-Positive T-Lymphocytes
Cancer Vaccines
Cell Line, Tumor
Epstein-Barr Virus Infections
Epstein-Barr Virus Nuclear Antigens
Genetic Vectors
HEK293 Cells
Herpesvirus 4, Human
Humans
Immunoglobulin G
Interferon-gamma
Leukocytes, Mononuclear
Lymphoma
Mice
Mice, Inbred C57BL
Mice, Transgenic
Rats
Treatment Outcome
Vaccination
Vaccinia virus
English The Epstein-Barr virus (EBV) is one of the predominant tumor viruses in humans, but so far no therapeutic or prophylactic vaccination against this transforming pathogen is available. We demonstrated that heterologous prime-boost vaccination with the nuclear antigen 1 of EBV (EBNA1), either targeted to the DEC205 receptor on DCs or expressed from a recombinant modified vaccinia virus Ankara (MVA) vector, improved priming of antigen-specific CD4+ T cell help. This help supported the expansion and maintenance of EBNA1-specific CD8+ T cells that are most efficiently primed by recombinant adenoviruses that encode EBNA1. These combined CD4+ and CD8+ T cell responses protected against EBNA1-expressing T and B cell lymphomas, including lymphoproliferations that emerged spontaneously after EBNA1 expression. In particular, the heterologous EBNA1-expressing adenovirus, boosted by EBNA1-encoding MVA vaccination, demonstrated protection as a prophylactic and therapeutic treatment for the respective lymphoma challenges. Our study shows that such heterologous prime-boost vaccinations against EBV-associated malignancies as well as symptomatic primary EBV infection should be further explored for clinical development.
Language
  • English
Open access status
bronze
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Persistent URL
https://sonar.ch/global/documents/297229
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