Abstract
Matching of symmetry at interfaces is a fundamental obstacle in molecular assembly. Virus‐like particles (VLPs) are important vaccine platforms against pathogenic threats, including Covid‐19. However, symmetry mismatch can prohibit vaccine nanoassembly. We established an approach for coupling VLPs to diverse antigen symmetries. SpyCatcher003 enabled efficient VLP conjugation and extreme thermal resilience. Many people had pre‐existing antibodies to SpyTag:SpyCatcher but less to the 003 variants. We coupled the computer‐designed VLP not only to monomers (SARS‐CoV‐2) but also to cyclic dimers (Newcastle disease, Lyme disease), trimers (influenza hemagglutinins), and tetramers (influenza neuraminidases). Even an antigen with dihedral symmetry could be displayed. For the global challenge of influenza, SpyTag‐mediated display of trimer and tetramer antigens strongly induced neutralizing antibodies. SpyCatcher003 conjugation enables nanodisplay of diverse symmetries towards generation of potent vaccines.
Highlights
As nanostructures grow and develop, there are often mismatches in size and symmetry at interfaces, including for crystal lattices,[1] metal-organic frameworks[2] and natural biological assemblies.[3]
Adenovirus has trimeric fibers extending from a capsid vertex with C5 (5-fold cyclic) symmetry, while Salmonellas injectisome has a C24 inner ring connecting to a C15 outer ring.[3]
Given the great problem of the failure of the cold-chain for global vaccine usage,[18] we used thermal and freeze-thaw stability analyses as surrogate assays to assess the resilience of the new virus-like particles (VLPs) platform
Summary
As nanostructures grow and develop, there are often mismatches in size and symmetry at interfaces, including for crystal lattices,[1] metal-organic frameworks[2] and natural biological assemblies.[3]. Genetic fusion of antigens to VLP subunits is hindered by different requirements for folding and posttranslational modifications, as well as symmetry mismatches.[9]
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