Targeting the nuclear antigen 1 of Epstein-Barr virus to the human endocytic receptor DEC-205 stimulates protective T-cell responses

Cagan Gurer, Till Strowig, Fabienne Brilot, Maggi Pack, Christine Trumpfheller, Frida Arrey, Chae Gyu Park, Ralph M. Steinman, Christian Münz

Research output: Contribution to journalArticlepeer-review

109 Scopus citations

Abstract

Dendritic cells (DCs) express many endo-cytic receptors that deliver antigens for major histocompatibility class (MHC) I and II presentation to CD8+ and CD4+ T cells, respectively. Here, we show that targeting Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA1) to one of them, the human multilectin DEC-205 receptor, in the presence of the DC maturation stimulus poly(l:C), expanded EBNA1-specific CD4+ and CD8+ memory T cells, and these lymphocytes could control the outgrowth of autologous EBV-infected B cells in vitro. In addition, using a novel mouse model with reconstituted human immune system components, we demonstrated that vaccination with αDEC-205-EBNA1 antibodies primed EBNA1-specific IFN-γ-secreting T cells and also induced anti-EBNA1 antibodies in a subset of immu- nized mice. Because EBNA1 is the one EBV antigen that is expressed in all proliferating cells infected with this virus, our data suggest that DEC-205 targeting should be explored as a vaccination approach against symptomatic primary EBV infection and against EBV-associated malignancies.

Original languageEnglish
Pages (from-to)1231-1239
Number of pages9
JournalBlood
Volume112
Issue number4
DOIs
StatePublished - 15 Aug 2008
Externally publishedYes

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