Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK.
MRC Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, OX3 9DS, UK.
Angew Chem Int Ed Engl. 2021 Jan 4;60(1):321-330. doi: 10.1002/anie.202009663. Epub 2020 Oct 27.
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.
界面处的对称性匹配是分子组装的一个基本障碍。病毒样颗粒（VLPs）是对抗包括 COVID-19 在内的致病威胁的重要疫苗平台。然而，对称性不匹配可能会阻止疫苗的纳米组装。我们建立了一种将 VLPs 与不同抗原对称性偶联的方法。SpyCatcher003 实现了高效的 VLP 缀合和极端的热稳定性。许多人已经对 SpyTag：SpyCatcher 有预先存在的抗体，但对 003 变体的抗体较少。我们不仅将计算机设计的 VLP 与单体（SARS-CoV-2）偶联，还与环状二聚体（新城疫、莱姆病）、三聚体（流感血凝素）和四聚体（流感神经氨酸酶）偶联。甚至可以展示具有二面体对称性的抗原。对于流感的全球性挑战，SpyTag 介导的三聚体和四聚体抗原展示强烈诱导了中和抗体。SpyCatcher003 缀合能够实现多种对称性的纳米展示，从而生成有效的疫苗。
