Synergistic adjuvant activity of immunostimulatory DNA and oil/water emulsions for immunization with HIV p55 gag antigen.
A synthetic oligonucleotide containing a previously identified adjuvant active CpG DNA sequence was evaluated for its ability to augment antibody and CTL responses to p55 gag from HIV-1 in mice. Surprisingly, the CpG oligonucleotide, although, it had previously been described as the most potent adjuvant sequence in mice for the particulate HbsAg, was ineffective when used in a simple combination with urea-solubilized p55 antigen. However, a potent adjuvant effect was observed with the CpG sequence when it was formulated with emulsions. Enhancement of antibody titer by CpG emulsion formulations was observed with urea-solubilized p55 antigen, however, significantly higher titers were obtained with p55 bound to polylactide-co-glycolide microparticles. In both cases IgG2a was enhanced in the presence of CpG. It appears likely that presentation of CpG with emulsions and particulate antigens enhances their delivery into antigen presenting cells (APC) and results in more effective presentation of antigen and adjuvant. To support this hypothesis, preliminary in vitro studies were undertaken to show upregulation of CD86 on mouse bone marrow-derived dendritic cells (BMDC) in vitro, following incubation with CpG formulations.
O'Hagan
D T
DT
Chiron Corporation, 4560 Horton Street, Emeryville, CA 94608, USA.
Singh
M
M
Kazzaz
J
J
Ugozzoli
M
M
Briones
M
M
Donnelly
J
J
Ott
G
G
D016915:AIDS Vaccines / Q000008:administration & dosage*; D000327:Adsorption; D000818:Animals; D017951:Antigen Presentation; D003713:Dendritic Cells / Q000276:immunology; D004357:Drug Synergism; D004655:Emulsions; D005260:Female; D015683:Gene Products, gag / Q000008:administration & dosage*; D015483:HIV Antibodies / Q000096:biosynthesis; D015699:HIV Envelope Protein gp120 / Q000008:administration & dosage; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology*; D007074:Immunoglobulin G / Q000096:biosynthesis; D066298:In Vitro Techniques; D019344:Lactic Acid; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage*; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D011498:Protein Precursors / Q000008:administration & dosage*; D012995:Solubility
D016915:AIDS Vaccines; C408982:CPG-oligonucleotide; D004655:Emulsions; D015683:Gene Products, gag; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D007074:Immunoglobulin G; D009838:Oligodeoxyribonucleotides; D011108:Polymers; D011498:Protein Precursors; C059767:p55 gag precursor protein, Human immunodeficiency virus 1; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid