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

Rühl, J. et al. (2019) Heterologous prime-boost vaccination protects against EBV antigen–expressing lymphomas. Journal of Clinical Investigation, 129(5), pp. 2071-2087. (doi: 10.1172/JCI125364) (PMID:30860494) (PMCID:PMC6486346)

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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.

Item Type:Articles
Additional Information:This study was supported by Cancer Research Switzerland (KFS- 4091-02-2017); the clinical research priority programs KFSPMS and KFSPHHLD of the University of Zurich; the Vontobel Foundation; the Baugarten Foundation, the Sobek Foundation; the Swiss Vaccine Research Institute; the Swiss MS Society; the Swiss National Science Foundation (310030_162560 and CRSII3_160708); and Worldwide Cancer Research (AICR 11-0516 and WCR 14-1033).
Glasgow Author(s) Enlighten ID:Wilson, Professor Joanna
Authors: Rühl, J., Citterio, C., Engelmann, C., Haigh, T., Dzionek, A., Dreyer, J., Khanna, R., Taylor, G. S., Wilson, J. B., Leung, C. S., and Munz, C.
College/School:College of Medical Veterinary and Life Sciences > School of Life Sciences
College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
Journal Name:Journal of Clinical Investigation
Publisher:Americal Society for Clinical Investigation
ISSN (Online):1558-8238
Published Online:12 March 2019

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