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Comparison of antibodies and carbohydrates to target vaccines to human dendritic cells via DC-SIGN

Paper ID Volume ID Publish Year Pages File Format Full-Text
7309 544 2012 11 PDF Available
Title
Comparison of antibodies and carbohydrates to target vaccines to human dendritic cells via DC-SIGN
Abstract

Vaccine efficacy is improved upon specific delivery to professional antigen (Ag) presenting cells, such as dendritic cells (DCs). Antigenicity and adjuvanticity of vaccine components can be enhanced by encapsulation within nanoparticle (NP) vaccine carriers that are targeted to the human DC-specific C-type lectin receptor DC-SIGN. Here we used two strategies to target vaccines components to DC-SIGN: 1) carbohydrates as natural receptor ligands and 2) receptor-specific antibodies (Abs). To determine the optimal targeting strategy, we coated NP vaccines harboring MHC class I or II-restricted Ags and the TLR ligands (TLRLs) poly I:C and resiquimod with either the DC-SIGN ligands Lewis-X (Lex), mannosylated lipoarabinomannan (ManLAM), glycosylated HIV protein gp120, or three distinct DC-SIGN Abs. Although, because of their lower MW, surface coating of NP vaccines with carbohydrates resulted in a higher number of surface molecules per NP than coating with Abs, NP vaccines carrying Abs were more effectively bound and internalized by human DCs than carriers harboring Lex, ManLAM or gp120. Furthermore, NP vaccines harboring TLRLs triggered significant induction of DC maturation markers when compared to those without TLRLs, irrespective of the targeting moiety. Ab- and gp120-mediated targeting induced equally high levels of proinflammatory cytokines and increased presentation of the MHC class I-restricted epitope. By contrast, presentation of the MHC class II-restricted epitope was more efficient upon Ab-mediated targeting than when using gp120, Lex or ManLAM. From these findings we conclude that receptor-specific Abs are more effective than carbohydrates for DC-targeted vaccination strategies.

Keywords
Antigenicity; Drug delivery; Immune response; Immunostimulation; Nanoparticle
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Comparison of antibodies and carbohydrates to target vaccines to human dendritic cells via DC-SIGN
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 33, Issue 16, June 2012, Pages 4229–4239
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us