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

Autor: 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
Přispěvatelé: University of Zurich, Leung, Carol S
Rok vydání: 2019
Předmět:
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
Zdroj: J Clin Invest
ISSN: 1558-8238
0021-9738
DOI: 10.1172/jci125364
Popis: 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.
Databáze: OpenAIRE
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