Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Alerts
  • Advertising/recruitment
  • Subscribe
  • Contact
  • Current Issue
  • Past Issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews ...
    • 100th Anniversary of Insulin's Discovery (Jan 2021)
    • Hypoxia-inducible factors in disease pathophysiology and therapeutics (Oct 2020)
    • Latency in Infectious Disease (Jul 2020)
    • Immunotherapy in Hematological Cancers (Apr 2020)
    • Big Data's Future in Medicine (Feb 2020)
    • Mechanisms Underlying the Metabolic Syndrome (Oct 2019)
    • Reparative Immunology (Jul 2019)
    • View all review series ...
  • Viewpoint
  • Collections
    • Recently published
    • In-Press Preview
    • Commentaries
    • Concise Communication
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • Recently published
  • In-Press Preview
  • Commentaries
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Alerts
  • Advertising/recruitment
  • Subscribe
  • Contact
Heterologous prime-boost vaccination protects against EBV antigen–expressing lymphomas
Julia Rühl, … , Carol S. Leung, Christian Münz
Julia Rühl, … , Carol S. Leung, Christian Münz
Published March 12, 2019
Citation Information: J Clin Invest. 2019;129(5):2071-2087. https://doi.org/10.1172/JCI125364.
View: Text | PDF
Research Article Immunology

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

  • Text
  • PDF
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.

Authors

Julia Rühl, Carmen Citterio, Christine Engelmann, Tracey Haigh, Andrzej Dzionek, Johannes Dreyer, Rajiv Khanna, Graham S. Taylor, Joanna B. Wilson, Carol S. Leung, Christian Münz

×

Figure 7

Characteristics of T cell responses toward EBNA1-induced B cell lymphomas with and without protective vaccination.

Options: View larger image (or click on image) Download as PowerPoint
Characteristics of T cell responses toward EBNA1-induced B cell lymphoma...
huDEC205-Tg mice were immunized with different combinations of vaccines for the prime and the boost, scheduled 10 days apart. Mice in the preventive group were challenged i.v. with 3 × 106 to 5 × 106 BL-E1 tumor cells 14 days after the boost. (A) At sacrifice, bulk splenocytes were harvested and stimulated with 1 μg/ml EBNA1 or control HCMV pp65 peptide pools. IFN-γ production was monitored by ICS in CD4+ gated cells. Data are shown as the mean ± SEM from 2 independent experiments with at least 5 mice per group. Statistical analyses was done using a 2-tailed Mann-Whitney U test. (B) After splenocyte stimulation, IFN-γ production was monitored by ICS in CD8+ gated cells. Data are shown as the mean ± SEM from 2 independent experiments with at least 5 mice per group. **P < 0.01 and ***P < 0.001; Kruskal-Wallis with Dunn’s multiple comparisons test (C) The CD4+/CD8+ T cell ratio was calculated using the percentages of each subset in the spleen. *P < 0.05; 1-way ANOVA with Tukey’s multiple comparisons test. (D) At sacrifice, bulk splenocytes were harvested and stained for PD-1 on CD8+ gated cells. Total PD-1+CD8+ cell amounts per spleen were calculated using the total splenocytes count. Data are shown as the mean ± SEM from 2 independent experiments with at least 5 mice per group. Mice with PBS treatment or vaccination and tumor injection were compared with mice that were only treated with PBS or vaccinated. **P < 0.01; Kruskal-Wallis with Dunn’s multiple comparisons test. (E) Splenic tissue was fixed in PFA and embedded in paraffin and then stained with H&E, αCD8, and αCD4. One representative image from each group is shown, along with an image of splenic cells from a PBS-treated mouse without tumor challenge. Scale bar: 20 μm.
Follow JCI:
Copyright © 2021 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts