Engineering a Rugged Nanoscaffold to Enhance Plug-and-Display Vaccination

作者: Theodora U. J. Bruun , Anne-Marie C. Andersson , Simon J. Draper , Mark Howarth

DOI: 10.1021/ACSNANO.8B02805

关键词: NanobiotechnologyIsopeptide bondAntigenProtein engineeringNanotechnologyVaccinationNanomedicineBioconjugationVirus-like particleChemistry

摘要: Nanoscale organization is crucial to stimulating an immune response. Using self-assembling proteins as multimerization platforms provides a safe and immunogenic system vaccinate against otherwise weakly antigens. Such are generally based on icosahedral viruses have led vaccines given millions of people. It unclear whether synthetic protein nanoassemblies would show similar potency. Here we take the computationally designed porous dodecahedral i301 60-mer rationally engineer this particle, giving mutated (mi3) with improved particle uniformity stability. To simplify conjugation nanoparticle, employ SpyCatcher fusion mi3, such that antigen interest linked SpyTag peptide can spontaneously couple through isopeptide bond formation (Plug-and-Display). SpyCatcher-mi3 expressed solubly high yields in Escherichia coli, more than 10-fold greater yield comparable phage-derived nanopartic...

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