Glycosidic Tn-based vaccines targeting dermal dendritic cells favor germinal center B-cell development and potent antibody response in the absence of adjuvant
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- Teresa Freire
- Institut Pasteur, Immune Regulation and Vaccinology Unit, Department of Immunology, Paris, France;
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- Xiaoming Zhang
- Institut Pasteur, Immune Regulation and Vaccinology Unit, Department of Immunology, Paris, France;
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- Edith Dériaud
- Institut Pasteur, Immune Regulation and Vaccinology Unit, Department of Immunology, Paris, France;
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- Christelle Ganneau
- Institut Pasteur, Unité de Chimie des Biomolécules, Paris, France;
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- Sophie Vichier-Guerre
- Unité de Recherche Associée, Centre National de la Recherche Scientifique 2128, Paris, France;
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- Elie Azria
- Department of Obstetrics and Gynecology, Groupe Hospitalier Bichat Claude Bernard, Paris, France;
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- Odile Launay
- Inserm U833, Paris, France;
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- Richard Lo-Man
- Institut Pasteur, Immune Regulation and Vaccinology Unit, Department of Immunology, Paris, France;
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- Sylvie Bay
- Institut Pasteur, Unité de Chimie des Biomolécules, Paris, France;
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- Claude Leclerc
- Institut Pasteur, Immune Regulation and Vaccinology Unit, Department of Immunology, Paris, France;
書誌事項
- 公開日
- 2010-11-04
- DOI
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- 10.1182/blood-2010-04-279133
- 公開者
- American Society of Hematology
この論文をさがす
説明
<jats:title>Abstract</jats:title><jats:p>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.</jats:p>
収録刊行物
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- Blood
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Blood 116 (18), 3526-3536, 2010-11-04
American Society of Hematology
