Author(s)
Yaroslav Tsybovsky
Published 9 Projects
COVID-19 Immunology Synthetic Biology Antibody Immune Evasion
Andrew B. Ward
Published 9 Projects
Immunology Microbiology Synthetic Biology Influenza Hemagglutinin Stalk
Content
Video Abstract (AI generated) (01:39) Paper Preprint Supplementary Information eLifeThe adaptive immune system is highly sensitive to arrayed antigens, and multivalent display of viral glycoproteins on symmetric scaffolds has been found to substantially increase the elicitation of antigen-specific antibodies. Motivated by the considerable promise of this strategy for next-generation anti-viral vaccines, we set out to design new self-assembling protein nanoparticles with geometries specifically tailored to scaffold ectodomains of different viral glycoproteins. We first designed and characterized homo-trimers from designed repeat proteins with N-terminal helices positioned to match the C termini of several viral glycoprotein trimers. Oligomers found to experimentally adopt the designed configuration were then used to generate nanoparticles with tetrahedral, octahedral, or icosahedral symmetry. Examples of all three target symmetries were experimentally validated by cryo-electron microscopy and several were assessed for their ability to display viral glycoproteins via genetic fusion. Electron microscopy and antibody binding experiments demonstrated that the designed nanoparticles display conformationally intact native-like HIV-1 Env, influenza hemagglutinin, and prefusion RSV F trimers in the predicted geometries. This work demonstrates that novel nanoparticle immunogens can be designed from the bottom up with atomic-level accuracy and provides a general strategy for precisely controlling epitope presentation and accessibility.
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Yaroslav Tsybovsky. (2021, Nov 1).Tailored Design of Protein Nanoparticle Scaffolds for Multivalent Presentation of Viral Glycoprotein Antigens[Video]. Scitok. https://scitok.com/project/p/883d6def
Ueda George. "Tailored Design of Protein Nanoparticle Scaffolds for Multivalent Presentation of Viral Glycoprotein Antigens" Scitok, uploaded by Tsybovsky Yaroslav, 1 Nov, 2021, https://scitok.com/project/p883d6def
Yaroslav Tsybovsky. "Tailored Design of Protein Nanoparticle Scaffolds for Multivalent Presentation of Viral Glycoprotein Antigens" Scitok. (Nov 1, 2021). https://scitok.com/project/p/883d6def
Yaroslav Tsybovsky (Nov 1, 2021). Tailored Design of Protein Nanoparticle Scaffolds for Multivalent Presentation of Viral Glycoprotein Antigens Scitok. https://scitok.com/project/p/883d6def
Yaroslav Tsybovsky. Tailored Design of Protein Nanoparticle Scaffolds for Multivalent Presentation of Viral Glycoprotein Antigens[video]. 2021 Nov 1. https://scitok.com/project/p/883d6def
@online{al2006link, title={ Tailored Design of Protein Nanoparticle Scaffolds for Multivalent Presentation of Viral Glycoprotein Antigens }, author={ Tsybovsky, Yaroslav }, organization={Scitok}, month={ Nov }, day={ 1 }, year={ 2021 }, url = {https://scitok.com/project/p/883d6def}, }