title: Dose sparing of CpG oligodeoxynucleotide vaccine adjuvants by nanoparticle delivery.
abstract: The main objective of these studies was to investigate whether the nanoparticle delivery has any immunopotentiation effect at modest doses of a few micro- or nanograms of CpG oligodeoxynucleotide (CpG ODN) and what would be the influence on T cell responses at such low doses. Various doses (5 to 0.05 microg) of a model CpG ODN adjuvant (#1826) along with 2 Lf tetanus toxoid (TT) were formulated in either nanoparticles using poly(D,L-lactic-co-glycolic acid) (PLGA) 50:50 co-polymer, or saline. Strong antigen specific ex vivo T cell proliferation was observed for the Balb/c mice receiving immunogens in nanoparticles. At 5 microg dose of CpG ODN, the T cell stimulation index (SI) was 241 as compared with 74 for the same dose when given in saline. Comparable SI value of 78 was observed at 100-fold lower dose (0.05 microg) using nanoparticles. Similarly, significantly higher (P<0.01) cytokine secretion was observed for nanoparticles groups. A ten-fold lower dose (0.5 microg instead of 5 microg) of CpG ODN in nanoparticles was adequate to obtain levels of IFN-gamma, TNF-alpha, and IL-2 comparable to those observed following immunisations in saline. The immunopotentiation effect of the particulate delivery on antibody response (total IgG and subtypes) was not so marked. These studies emphasise that antigen delivery in biodegradable nanoparticles can facilitate induction of strong T cell responses, particularly of the Th1 type, at extremely lower doses of CpG ODN. Such reduction in the effective dose would be advantageous for minimising the potential side effects of these novel adjuvants.
authors.affiliation: Faculty of Pharmacy and Pharmaceutical Sciences, 3118 Dentistry Pharmacy Center, University of Alberta, Edmonton, T6G 2N8, Canada.
authors.forename: Manish
authors.initials: M
authors.lastname: Diwan
authors.forename: Praveen
authors.initials: P
authors.lastname: Elamanchili
authors.forename: Min
authors.initials: M
authors.lastname: Cao
authors.forename: John
authors.initials: J
authors.lastname: Samuel
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D007111:Immunity, Cellular / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D019344:Lactic Acid / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D049329:Nanostructures / Q000737:chemistry*; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry; D012995:Solubility; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D013745:Tetanus Toxoid / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D014612:Vaccines / Q000737:chemistry* / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000942:Antigens, Bacterial; C408982:CPG-oligonucleotide; D016207:Cytokines; D007074:Immunoglobulin G; D009838:Oligodeoxyribonucleotides; D011108:Polymers; D013745:Tetanus Toxoid; D014612:Vaccines; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid