Peptide Based Nanoparticles as a Platform for Vaccine Design

摘要

Artificial paniculate systems such as polymeric beads and liposomes have many applications in drug delivery, drag targeting, antigen display, vaccination, and other technologies. We have recently designed a novel type of nanoparticle with regular icosahedral symmetry and a diameter of about 16 nm, which self-assembles from single polypeptide chains. The geometry of the nanoparticle and its resemblance to small viruses will trigger a strong immune response based on repetitive antigen display - a concept that now is increasingly exploited for producing novel vaccines that yield high titers of specific antibodies by using virus-like-particles as repetitive antigen display systems. Such de novo designed nanoparticles eliminates the need for virus-based designs, and allow for high flexibility in vaccine design. Epitopes of any pathogen can readily be engineered onto the surface of the nanoparticle, thus allowing for the easy generation of a whole variety of different vaccines. To validate our system as a novel platform for vaccine design, we have designed nanoparticles that display antigenic sequences at their surface. As a test model we have inserted the pilin sequence from Pseudomonas at the C-terminus of the constructs. Immunization experiments using such nanoparticles for repetitive antigen display are described and presented.