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Overcoming Symmetry Mismatch in Vaccine Nanoassembly through Spontaneous Amidation
Author(s) -
Rahikainen Rolle,
Rijal Pramila,
Tan Tiong Kit,
Wu HungJen,
Andersson AnneMarie C.,
Barrett Jordan R.,
Bowden Thomas A.,
Draper Simon J.,
Townsend Alain R.,
Howarth Mark
Publication year - 2021
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202009663
Subject(s) - trimer , tetramer , epitope , symmetry (geometry) , antigen , virology , chemistry , dimer , biology , genetics , biochemistry , mathematics , geometry , organic chemistry , enzyme
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.