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 Blood, 15 August 2008, Vol. 112, No. 4, pp. 1231-1239.
Prepublished online as a Blood First Edition Paper on June 2, 2008; DOI 10.1182/blood-2008-03-148072.

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IMMUNOBIOLOGY

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

Cagan Gurer1,2, Till Strowig1,2, Fabienne Brilot1,2, Maggi Pack2,3, Christine Trumpfheller2,3, Frida Arrey1,2, Chae Gyu Park2,3, Ralph M. Steinman2,3, and Christian Münz1,2

1 Laboratory of Viral Immunobiology, 2 Christopher H. Browne Center for Immunology and Immune Diseases, and 3 Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, NY

Dendritic cells (DCs) express many endocytic 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(I: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 {alpha}DEC-205-EBNA1 antibodies primed EBNA1-specific IFN-{gamma}–secreting T cells and also induced anti-EBNA1 antibodies in a subset of immunized 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.


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T. Strowig, C. Gurer, A. Ploss, Y.-F. Liu, F. Arrey, J. Sashihara, G. Koo, C. M. Rice, J. W. Young, A. Chadburn, et al.
Priming of protective T cell responses against virus-induced tumors in mice with human immune system components
J. Exp. Med., June 8, 2009; 206(6): 1423 - 1434.
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