Glycosidic Tn-based vaccines targeting dermal dendritic cells favor germinal center B-cell development and potent antibody response in the absence of adjuvant.

نویسندگان

  • Teresa Freire
  • Xiaoming Zhang
  • Edith Dériaud
  • Christelle Ganneau
  • Sophie Vichier-Guerre
  • Elie Azria
  • Odile Launay
  • Richard Lo-Man
  • Sylvie Bay
  • Claude Leclerc
چکیده

In vivo targeting of C-type lectin receptors is an effective strategy for increasing antigen uptake and presentation by dendritic cells (DCs). To induce efficient immune response, glycosylated tumor-associated Tn antigens were used to target DCs through binding to macrophage galactose-type lectin (MGL). The capacity of Tn-glycosylated antigens-and the multiple antigenic glycopeptide Tn3 therapeutic candidate vaccine-to target mouse and human MGL(+) DCs are demonstrated, especially regarding dermal DCs. In mice, MGL(+) CD103(-) dermal DCs efficiently captured and processed glycosylated Tn antigen in vivo, inducing a potent major histocompatibility complex (MHC) class II-restricted T-cell response. Intradermal immunization with Tn-glycopeptides induced high levels of Th2 cytokines-even in the presence of unmethylated cytosine-phosphate-guanosine-and was associated with increased expansion of the germinal center B-cell population. Therefore, MGL acts as an efficient endocytic antigen receptor on dermal DCs in vivo, able to prime Tn-specific T- and B-cell responses. Moreover, even in the absence of adjuvant, immunization with this glycosidic Tn-based vaccine induced high levels of anti-Tn antibody responses, recognizing human tumor cells. In vivo DC-targeting strategies, based on Tn-MGL interactions, constitute a promising strategy for enhancing antigen presentation and inducing potent antibody response.

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عنوان ژورنال:
  • Blood

دوره 116 18  شماره 

صفحات  -

تاریخ انتشار 2010