title: Peptide-conjugated PAMAM dendrimer as a universal DNA vaccine platform to target antigen-presenting cells.
abstract: 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.
authors: Department of Microbiology and Immunology, Sylvester Cancer Center, Miller School of Medicine, University of Miami, Miami, USA. pdaftarian@med.miami.edu
authors: Pirouz
authors: P
authors: Daftarian
authors: Angel E
authors: AE
authors: Kaifer
authors: Wei
authors: W
authors: Li
authors: Bonnie B
authors: BB
authors: Blomberg
authors: Daniela
authors: D
authors: Frasca
authors: Felix
authors: F
authors: Roth
authors: Raquibul
authors: R
authors: Chowdhury
authors: Eric A
authors: EA
authors: Berg
authors: Jordan B
authors: JB
authors: Fishman
authors: Husain A
authors: HA
authors: Al Sayegh
authors: Pat
authors: P
authors: Blackwelder
authors: Luca
authors: L
authors: Inverardi
authors: Victor L
authors: VL
authors: Perez
authors: Vance
authors: V
authors: Lemmon
authors: Paolo
authors: P
authors: Serafini
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004247:DNA / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D050091:Dendrimers / Q000737:chemistry*; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008546:Melanoma, Experimental / Q000276:immunology / Q000473:pathology / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010455:Peptides / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology; D055672:Static Electricity; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D014611:Vaccination / Q000379:methods; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
chemical_list: D050091:Dendrimers; D000949:Histocompatibility Antigens Class II; C104700:PAMAM Starburst; D010455:Peptides; D019444:Vaccines, DNA; D004247:DNA