Stable assemblies of cationic bilayer fragments and CpG oligonucleotide with enhanced immunoadjuvant activity in vivo.
The cationic lipid dioctadecyldimethylammonium bromide (DODAB) and the CpG oligonucleotide (CpG) have been separately used as potent immunoadjuvants driving Th1 responses. Here DODAB bilayer fragments (BF) and CpG (5'-TTGACGTTCG-3') assemblies have their physical properties and immunoadjuvant activity determined using ovalbumin (OVA) as a model antigen. At 0.1 mg/mL OVA, the dependence of DODAB BF/OVA size and zeta-potential on time and [DODAB] establishes 0.1 mM DODAB as suitable for obtaining stable and cationic DODAB BF/OVA assemblies. At 0.1 mM DODAB, 0.1 mg/mL OVA and 0.006 mM CpG, the zeta-potential is zero. At [CpG]>0.006 mM, good colloidal stability for the anionic assemblies is due to charge overcompensation. At 0.020 mM CpG, these DODAB BF/OVA/CpG assemblies are highly effective in vivo generating responses similar to those elicited by the stable and cationic DODAB BF/OVA. The anti-OVA DTH reaction and the secretion of IFN-gamma and IL-12 are 6, 42 and 9 times larger for the DODAB BF/OVA/CpG-immunized mice than the same responses by OVA-immunized mice, respectively. This work shows for the first time that charge of small assemblies is not important to determine the immune response.
Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, CP 26077, CEP 05513-970, São Paulo, SP, Brazil.
Julio H K
JH
Rozenfeld
Sandriana R
SR
Silva
Priscila A
PA
Ranéia
Eliana
E
Faquim-Mauro
Ana M
AM
Carmona-Ribeiro
D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000737:chemistry; D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D017951:Antigen Presentation / Q000276:immunology; D002412:Cations; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry*; D004355:Drug Stability; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D008051:Lipid Bilayers / Q000737:chemistry* / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D010047:Ovalbumin / Q000008:administration & dosage* / Q000737:chemistry / Q000276:immunology; D010316:Particle Size; D000644:Quaternary Ammonium Compounds / Q000737:chemistry* / Q000276:immunology; D013499:Surface Properties
D000276:Adjuvants, Immunologic; D002412:Cations; C516146:CpG ODN-OVA; D016207:Cytokines; D004337:Drug Carriers; D007074:Immunoglobulin G; D008051:Lipid Bilayers; D009838:Oligodeoxyribonucleotides; D000644:Quaternary Ammonium Compounds; C015831:dimethyldioctadecylammonium; D010047:Ovalbumin