PCSK9 Hapten Multicopy Displayed onto Carrier Protein Nanoparticle: An Antiatherosclerosis Vaccine.

Abstract

In recent years, various vaccination strategies have shed new light on the treatment of atherosclerosis. Proprotein convertase subtilisin/Kexin type 9 (PCSK9) is a hot target in the development of antiatherosclerosis vaccine. However, the efficacy of conventional PCSK9 is largely limited by poor immunogenicity and low hapten density. Therefore, we hypothesized whether a nanostructure synthesized by self-assembled carrier protein accompanied by multicopy hapten display could improve the efficacy of vaccine. In this study, bovine serum albumin (BSA) was self-assembled into sub-100 nm nanoparticles via an intermolecular disulfide network as the inner core. Then, sequences of PCSK9 were conjugated onto the surface of nanoparticles by click chemistry to consequently form an orderly structured of nanovaccine with repetitive hapten display. Compared with conventional PCSK9 peptide vaccine, our immunization study demonstrated that the PCSK9 multicopy display nanovaccine (PMCDN) was able to induce higher titers of PCSK9 antibody and more efficient lymph node drainage and improve endocytosis by antigen presenting cells.