Poly-L-lysine-coated nanoparticles: a potent delivery system to enhance DNA vaccine efficacy.
DNA formulations provide the basis for safe and cost efficient vaccines. However, naked plasmid DNA is only poorly immunogenic and new effective delivery strategies are needed to enhance the potency of DNA vaccines. In this study, we present a novel approach for the delivery of DNA vaccines using inert poly-L-lysine (PLL) coated polystyrene particles, which greatly enhance DNA immunogenicity. Intradermal injection of plasmid DNA encoding for chicken egg ovalbumin (OVA) complexed with PLL-coated polystyrene nanoparticles induced high levels of CD8 T cells as well as OVA-specific antibodies in C57BL/6 mice and furthermore inhibited tumour growth after challenge with the OVA expressing EG7 tumour cell line. Importantly, vaccine efficacy depended critically on the size of the particles used as well as on the presence of the PLL linker. Our data show that PLL-coated polystyrene nanoparticles of 0.05 microm but not 0.02 microm or 1.0 microm in diameter are highly effective for the delivery of DNA vaccines.
Minigo
Gabriela
G
Vaccine and Infectious Diseases Laboratory, The Burnet Institute incorporating the Austin Research Institute, Austin Hospital, Studley Road, Heidelberg, Victoria 3084, Australia.
Scholzen
Anja
A
Tang
Choon K
CK
Hanley
Jennifer C
JC
Kalkanidis
Martha
M
Pietersz
Geoffrey A
GA
Apostolopoulos
Vasso
V
Plebanski
Magdalena
M
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical; D003713:Dendritic Cells / Q000276:immunology; D004337:Drug Carriers; D016503:Drug Delivery Systems; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000276:immunology / Q000517:prevention & control; D010047:Ovalbumin / Q000276:immunology; D010316:Particle Size; D010957:Plasmids / Q000235:genetics / Q000276:immunology; D011107:Polylysine / Q000494:pharmacology*; D011137:Polystyrenes; D019444:Vaccines, DNA / Q000276:immunology*
D000276:Adjuvants, Immunologic; D004337:Drug Carriers; D011137:Polystyrenes; D019444:Vaccines, DNA; D011107:Polylysine; D010047:Ovalbumin