TY - JOUR
T1 - Heterologous prime-boost vaccination protects against EBV antigen-expressing lymphomas
AU - Ruhl, Julia
AU - Citterio, C
AU - Engelmann, Christine
AU - Haigh, Tracey
AU - Dzionek, A
AU - Dreyer, J
AU - Khanna, Rajiv
AU - Taylor, Graham
AU - Wilson, J
AU - Leung, C
AU - Munz, Christian
PY - 2019/5/1
Y1 - 2019/5/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85062859578&partnerID=8YFLogxK
U2 - 10.1172/JCI125364
DO - 10.1172/JCI125364
M3 - Article
SN - 0021-9738
VL - 129
SP - 2071
EP - 2087
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
IS - 5
ER -