Enhanced Humoral Responses Induced by Targeting of Antigen to Murine Dendritic Cells.
Dendritic cells (DCs) are superior in their ability to induce and control adaptive immune responses. These qualities have motivated the hypothesis that targeted delivery of antigen to DCs in vivo may be an effective way of enhancing immunization. Recent results show that antigen targeted to certain DC surface molecules may indeed induce robust immune responses. Targeting of antigen to DCs can be accomplished by the means of monoclonal antibodies. This study compared the humoral responses induced in mice by in vivo targeting of DCs using monoclonal antibodies specific for CD11c, CD36, CD205, Clec6A, Clec7A, Clec9A, Siglec-H and PDC-TREM. The results demonstrate that antigen delivery to different targets on DCs in vivo gives rise to humoral responses that differ in strength. Targeting of antigen to CD11c, CD36, CD205, Clec6A, Clec7A and PDC-TREM induced significantly stronger antibody responses compared to non-targeted isotype-matched controls. Targeting of Clec9A and Siglec-H did not lead to efficient antibody responses, which may be due to unfavourable properties of the targeting antibody, in which case, other antibodies with the same specificity might elicit a different outcome. Anti-CD11c was additionally used for elucidating the impact of the route of vaccination, and the results showed only minor differences between the antibody responses induced after immunization either s.c., i.v. or i.p. Altogether, these data show that targeting of different surface molecules on DCs result in very different antibody responses and that, even in the absence of adjuvants, strong humoral responses was induced.
Department of Clinical Immunology, Aalborg University Hospital, Aalborg, Denmark.|Laboratory of Immunology, Department of Health Science and Technology, Aalborg University, Aalborg, Denmark.
L H
LH
Pugholm
Laboratory of Immunology, Department of Health Science and Technology, Aalborg University, Aalborg, Denmark.
L R
LR
Petersen
Department of Clinical Immunology, Aalborg University Hospital, Aalborg, Denmark.
E K L
EK
Søndergaard
Department of Clinical Immunology, Aalborg University Hospital, Aalborg, Denmark.
K
K
Varming
Laboratory of Immunology, Department of Health Science and Technology, Aalborg University, Aalborg, Denmark.
R
R
Agger
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000917:Antibody Formation / Q000276:immunology; D000941:Antigens / Q000008:administration & dosage*; D000954:Antigens, Surface / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D016503:Drug Delivery Systems; D005260:Female; D056724:Immunity, Humoral / Q000276:immunology; D007114:Immunization / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats
D000911:Antibodies, Monoclonal; D000941:Antigens; D000954:Antigens, Surface