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Peptide Based Nanoparticles as a Platform for Vaccine Design

S.K. Raman, D.J. Kao, D. Tropel, A. Graff, G. Machaidze, R.S. Hodges and P. Burkhard
Biozentrum, CH

vaccine design, nanoparticle, self-assembly, immunology

To-date vaccines for many of the dreadful diseases such as Tuberculosis, Malaria, AIDS and Hepatitis are still ineffective or unavailable. Peptide based vaccines have been developed but because of their poor immunogenic response and the toxicity issue of the adjuvants used along with peptides still remains a concern. Here we describe the structure-based design of peptidic nanoparticles with regular polyhedral symmetry that mimic the architecture of viruses. Such peptide based nanoparticles represent an ideal repetitive antigen display system and may be used as a platform for the design of synthetic vaccines. Repetitive antigen display has been shown to strongly increase the immunogenicity of a given epitope and novel vaccines based on virus-like particles are gaining increased interest in the field of vaccine design. 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 of such different sized nanoparticles conjugated with the Pseudomonas pilin sequence (and also with other model surface antigens) in rabbits have recently been initiated.

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