title: Co-administration of a CpG adjuvant (VaxImmune, CPG 7909) with CETP vaccines increased immunogenicity in rabbits and mice.
abstract: Cholesteryl ester transfer protein (CETP) is a plasma glycoprotein that facilitates the transfer of neutral lipids and phospholipids between lipoproteins and contributes to the regulation of the plasma concentration of high density lipoprotein cholesterol (HDL-C). Vaccines have been developed that elicit antibodies that bind to and reduce the lipid transfer function of CETP as a way to increase the plasma concentration of HDL-C and prevent or treat atherosclerosis. This study assessed the immunogenicity of two vaccine peptides. The first, CETi-1, is a dimerized synthetic peptide, including residues 461-476 of human CETP and residues 830-843 of tetanus toxoid, TT(830-843). The second, PADRE-CETP, is a monomeric peptide, in which a PADRE T cell epitope (aK-Cha-VAAWTLKAa) replaces the TT(830-843) T cell epitope of CETi-1. Both peptides were formulated with aluminum-containing adjuvants (Alhydrogel), and tested in mice and rabbits with or without the co-administration of the investigational TLR9 agonist VaxImmune (CPG 7909). In both mice and rabbits, the vaccine peptide utilizing the PADRE T cell epitope elicited stronger anti-CETP antibody responses than the CETi-1 vaccine. Also, co-administration of VaxImmune enhanced the anti-CETP antibody responses to both vaccines. Isotype analysis of the murine anti-CETP antibody response to both vaccines demonstrated a switch from IgG1 to IgG2a upon co-administration of VaxImmune. We conclude that (1) the PADRE T cell epitope is more potent than the TT(830-843) epitope in providing help for the anti-CETP antibody response; and (2) co-administration of VaxImmune with either vaccine increased immunogenicity as measured by antibody response.
authors.affiliation: AVANT Immunotherapeutics, Inc., Needham, Massachusetts 02494, USA. lthomas@avantimmune.com
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Thomas
authors.forename: Russell A
authors.initials: RA
authors.lastname: Hammond
authors.forename: Eric M
authors.initials: EM
authors.lastname: Forsberg
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Geoghegan-Barek
authors.forename: Brad H
authors.initials: BH
authors.lastname: Karalius
authors.forename: Henry C
authors.initials: HC
authors.lastname: Marsh
authors.forename: Charles W
authors.initials: CW
authors.lastname: Rittershaus
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000494:pharmacology; D000536:Aluminum Hydroxide / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D000906:Antibodies / Q000097:blood; D050197:Atherosclerosis / Q000517:prevention & control* / Q000628:therapy*; D053480:Cholesterol Ester Transfer Proteins / Q000276:immunology*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage* / Q000494:pharmacology; D011817:Rabbits; D022223:Vaccines, Subunit / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000906:Antibodies; C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; D007074:Immunoglobulin G; D009838:Oligodeoxyribonucleotides; C483020:ProMune; D022223:Vaccines, Subunit; D000536:Aluminum Hydroxide