Overcoming Symmetry Mismatch in Vaccine Nanoassembly through Spontaneous Amidation.
Angew Chem Int Ed Engl
; 60(1): 321-330, 2021 01 04.
Article
in En
| MEDLINE
| ID: mdl-32886840
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 SpyTagSpyCatcher 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Nanostructures
/
Vaccines, Virus-Like Particle
/
COVID-19 Vaccines
Limits:
Humans
Language:
En
Journal:
Angew Chem Int Ed Engl
Year:
2021
Document type:
Article
Affiliation country:
United kingdom