1. Heterologous prime-boost vaccination protects against EBV antigen–expressing lymphomas
- Author
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Christian Münz, Julia Rühl, Andrzej Dzionek, Graham S. Taylor, Rajiv Khanna, Joanna B. Wilson, Carmen Citterio, Christine Engelmann, Carol S. Leung, Johannes H. Dreyer, Tracey A. Haigh, University of Zurich, and Leung, Carol S
- Subjects
CD4-Positive T-Lymphocytes ,0301 basic medicine ,Epstein-Barr Virus Infections ,Herpesvirus 4, Human ,Lymphoma ,viruses ,Priming (immunology) ,2700 General Medicine ,CD8-Positive T-Lymphocytes ,10263 Institute of Experimental Immunology ,Mice ,chemistry.chemical_compound ,0302 clinical medicine ,hemic and lymphatic diseases ,Vaccination ,General Medicine ,Treatment Outcome ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Research Article ,T cell ,Genetic Vectors ,Heterologous ,Mice, Transgenic ,610 Medicine & health ,Vaccinia virus ,Biology ,complex mixtures ,Cancer Vaccines ,Virus ,Interferon-gamma ,03 medical and health sciences ,Antigen ,Cell Line, Tumor ,otorhinolaryngologic diseases ,medicine ,Animals ,Humans ,B cell ,Virology ,Rats ,Mice, Inbred C57BL ,stomatognathic diseases ,HEK293 Cells ,030104 developmental biology ,Epstein-Barr Virus Nuclear Antigens ,chemistry ,Immunoglobulin G ,Leukocytes, Mononuclear ,Commentary ,570 Life sciences ,biology ,Vaccinia ,CD8 - Abstract
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.
- Published
- 2019