title: Enhanced antibody production in mice to the malaria antigen AMA1 by CPG 7909 requires physical association of CpG and antigen.
abstract: CpG oligodeoxynucleotides are potent immunostimulants. In this study, CPG 7909 was formulated with the recombinant Plasmodium falciparum protein AMA1-C1 adsorbed to Alhydrogel (aluminum hydroxide) and used to immunize mice. Mice receiving free CPG 7909 in a separate same site injection to the AMA1-C1/Alhydrogel had the same antibody responses as mice receiving AMA1-C1/Alhydrogel alone. For mice immunized with CPG 7909 bound to the AMA1-C1/Alhydrogel formulation, there was a bell shaped CPG 7909 dose-response curve with the highest antibody response co-incident with the concentration of CPG 7909 that saturated binding to the Alhydrogel. At a higher CPG 7909 dose where 74% was unbound, there was no enhancement of response over AMA1-C1/Alhydrogel alone. Our results suggest that the adjuvant effects of CpGs are optimal when adsorbed to Alhydrogel and highlight the need for careful characterization of the vaccine formulation.
authors.affiliation: Malaria Vaccine Development Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 5640 Fishers Lane, Rockville, MD 20852, USA.
authors.forename: Gregory E D
authors.initials: GE
authors.lastname: Mullen
authors.forename: Joan A
authors.initials: JA
authors.lastname: Aebig
authors.forename: Gelu
authors.initials: G
authors.lastname: Dobrescu
authors.forename: Kelly
authors.initials: K
authors.lastname: Rausch
authors.forename: Lynn
authors.initials: L
authors.lastname: Lambert
authors.forename: Carole A
authors.initials: CA
authors.lastname: Long
authors.forename: Aaron P
authors.initials: AP
authors.lastname: Miles
authors.forename: Allan
authors.initials: A
authors.lastname: Saul
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood*; D000953:Antigens, Protozoan / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D008288:Malaria / Q000276:immunology*; D017780:Malaria Vaccines / Q000276:immunology*; D051379:Mice; D009838:Oligodeoxyribonucleotides / Q000276:immunology*; D010963:Plasmodium falciparum / Q000276:immunology*
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D007074:Immunoglobulin G; D017780:Malaria Vaccines; D009838:Oligodeoxyribonucleotides; C483020:ProMune