title: CpG ODN and ISCOMATRIX adjuvant: a synergistic adjuvant combination inducing strong T-Cell IFN-γ responses.
abstract: For the induction of robust humoral and cellular immune responses, a strong rationale exists to use vaccine-adjuvant combinations possessing both immune modulatory and enhanced delivery capabilities. Herein, we evaluated the combination of 2 different adjuvants, a TLR9 agonist, composed of synthetic oligodeoxynucleotides (ODN) containing immunostimulatory CpG motifs (CpG), and ISCOMATRIX adjuvant (ISCOMATRIX), composed of saponin, phospholipid, and cholesterol, which possesses both immunostimulatory and delivery properties. While both individual adjuvants have been shown effective in numerous preclinical and clinical studies, it is likely that for optimal adjuvant activity a combined adjuvant approach will be necessary. Herein, using three different antigens, namely, hepatitis B surface antigen (HBsAg), ovalbumin (OVA), and influenza A haemagglutinin antigen (HA), we show in mice that some adjuvant effects of CpG and ISCOMATRIX are further enhanced if they are used in combination. In particular, with all three antigens, IFN-γ levels were greatly increased with the CpG/ISCOMATRIX combination. The ability of the CpG/ISCOMATRIX combination to induce antitumor responses when administered with OVA following administration to mice of a highly metastatic OVA-secreting tumor cell line (B16-OVA melanoma) was also demonstrated. Thus the CpG/ISCOMATRIX combination may prove to be a valuable tool in the development of novel or improved vaccines.
authors.affiliation: Pfizer Vaccine Research, Ottawa Laboratories, 340 Terry Fox Drive, Suite 200, Ottawa, ON, Canada K2K 3A2. michael.mccluskie@pfizer.com
authors.forename: Michael J
authors.initials: MJ
authors.lastname: McCluskie
authors.forename: Risini D
authors.initials: RD
authors.lastname: Weeratna
authors.forename: Dana M
authors.initials: DM
authors.lastname: Evans
authors.forename: Shawn
authors.initials: S
authors.lastname: Makinen
authors.forename: Debbie
authors.initials: D
authors.lastname: Drane
authors.forename: Heather L
authors.initials: HL
authors.lastname: Davis
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology; D002784:Cholesterol / Q000008:administration & dosage*; D004338:Drug Combinations; D004357:Drug Synergism; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D007113:Immunity, Innate / Q000187:drug effects / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism*; D051379:Mice; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage*; D010743:Phospholipids / Q000008:administration & dosage*; D012503:Saponins / Q000008:administration & dosage*; D013601:T-Lymphocytes / Q000187:drug effects; D051217:Toll-Like Receptor 9 / Q000819:agonists / Q000378:metabolism; D014612:Vaccines / Q000276:immunology
chemical_list: D000941:Antigens; C408982:CPG-oligonucleotide; D004338:Drug Combinations; C493786:ISCOMATRIX; D009838:Oligodeoxyribonucleotides; D010743:Phospholipids; D012503:Saponins; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9; D014612:Vaccines; D007371:Interferon-gamma; D002784:Cholesterol