Targeted PLGA nano- but not microparticles specifically deliver antigen to human dendritic cells via DC-SIGN in vitro.
Vaccine efficacy is strongly enhanced by antibody-mediated targeting of vaccine components to dendritic cells (DCs), which are professional antigen presenting cells. However, the options to link antigens or immune modulators to a single antibody are limited. Here, we engineered versatile nano- and micrometer-sized slow-release vaccine delivery vehicles that specifically target human DCs to overcome this limitation. The nano- (NPs) and microparticles (MPs), with diameters of approximately 200nm and 2microm, consist of a PLGA core coated with a polyethylene glycol-lipid layer carrying the humanized targeting antibody hD1, which does not interact with complement or Fc receptors and recognizes the human C-type lectin receptor DC-SIGN on DCs. We studied how these particles interact with human DCs and blood cells, as well as the kinetics of PLGA-encapsulated antigen degradation within DCs. Encapsulation of antigen resulted in almost 38% degradation for both NPs and MPs 6days after particle ingestion by DCs, compared to 94% when nonencapsulated, soluble antigen was used. In contrast to the MPs, which were taken up rather nonspecifically, the NPs effectively targeted human DCs. Consequently, targeted delivery only improved antigen presentation of NPs and induced antigen-dependent T cell responses at 10-100 fold lower concentrations than nontargeted NPs.
Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Medical Centre, Nijmegen, The Netherlands.
Luis J
LJ
Cruz
Paul J
PJ
Tacken
Remco
R
Fokkink
Ben
B
Joosten
Martien Cohen
MC
Stuart
Fernando
F
Albericio
Ruurd
R
Torensma
Carl G
CG
Figdor
D000906:Antibodies / Q000276:immunology / Q000378:metabolism; D017951:Antigen Presentation / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism; D000941:Antigens / Q000276:immunology / Q000378:metabolism; D015815:Cell Adhesion Molecules; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D016503:Drug Delivery Systems; D006801:Humans; D019344:Lactic Acid; D037181:Lectins, C-Type / Q000276:immunology* / Q000378:metabolism; D011092:Polyethylene Glycols / Q000378:metabolism; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011956:Receptors, Cell Surface; D014612:Vaccines / Q000276:immunology / Q000378:metabolism; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D000906:Antibodies; D000941:Antigens; D015815:Cell Adhesion Molecules; D019344:Lactic Acid; D037181:Lectins, C-Type; D011092:Polyethylene Glycols; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011956:Receptors, Cell Surface; D014612:Vaccines; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin