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.