Glycosidic Tn-based vaccines targeting dermal dendritic cells favor germinal center B-cell development and potent antibody response in the absence of adjuvant.
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.
Freire
Teresa
T
Immune Regulation and Vaccinology Unit, Department of Immunology, Institut Pasteur, 25-28 Rue du Dr. Roux, Paris Cedex 15, France.
Zhang
Xiaoming
X
Dériaud
Edith
E
Ganneau
Christelle
C
Vichier-Guerre
Sophie
S
Azria
Elie
E
Launay
Odile
O
Lo-Man
Richard
R
Bay
Sylvie
S
Leclerc
Claude
C
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D015295:Antigens, Tumor-Associated, Carbohydrate / Q000737:chemistry / Q000276:immunology*; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D018858:Germinal Center / Q000166:cytology*; D006031:Glycosylation; D006801:Humans; D007801:Langerhans Cells / Q000276:immunology*; D037102:Lectins / Q000276:immunology; D037181:Lectins, C-Type / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D014614:Vaccines, Synthetic / Q000737:chemistry / Q000276:immunology
D015295:Antigens, Tumor-Associated, Carbohydrate; D037102:Lectins; D037181:Lectins, C-Type; C506225:MGL lectin, human; D010455:Peptides; C040286:Tn antigen; D014614:Vaccines, Synthetic