Peptide-conjugated PAMAM dendrimer as a universal DNA vaccine platform to target antigen-presenting cells.

Published

Journal Article

DNA-based vaccines hold promise to outperform conventional antigen-based vaccines by virtue of many unique features. However, DNA vaccines have thus far fallen short of expectations, due in part to poor targeting of professional antigen-presenting cells (APC) and low immunogenicity. In this study, we describe a new platform for effective and selective delivery of DNA to APCs in vivo that offers intrinsic immune-enhancing characteristics. This platform is based on conjugation of fifth generation polyamidoamine (G5-PAMAM) dendrimers, a DNA-loading surface, with MHC class II-targeting peptides that can selectively deliver these dendrimers to APCs under conditions that enhance their immune stimulatory potency. DNA conjugated with this platform efficiently transfected murine and human APCs in vitro. Subcutaneous administration of DNA-peptide-dendrimer complexes in vivo preferentially transfected dendritic cells (DC) in the draining lymph nodes, promoted generation of high affinity T cells, and elicited rejection of established tumors. Taken together, our findings show how PAMAM dendrimer complexes can be used for high transfection efficiency and effective targeting of APCs in vivo, conferring properties essential to generate effective DNA vaccines.

Full Text

Duke Authors

Cited Authors

  • Daftarian, P; Kaifer, AE; Li, W; Blomberg, BB; Frasca, D; Roth, F; Chowdhury, R; Berg, EA; Fishman, JB; Al Sayegh, HA; Blackwelder, P; Inverardi, L; Perez, VL; Lemmon, V; Serafini, P

Published Date

  • December 15, 2011

Published In

Volume / Issue

  • 71 / 24

Start / End Page

  • 7452 - 7462

PubMed ID

  • 21987727

Pubmed Central ID

  • 21987727

Electronic International Standard Serial Number (EISSN)

  • 1538-7445

Digital Object Identifier (DOI)

  • 10.1158/0008-5472.CAN-11-1766

Language

  • eng

Conference Location

  • United States