Engineering a Rugged Nanoscaffold To Enhance Plug-and-Display Vaccination.

ACS Nano
Theodora U J BruunMark Howarth

Abstract

Nanoscale organization is crucial to stimulating an immune response. Using self-assembling proteins as multimerization platforms provides a safe and immunogenic system to vaccinate against otherwise weakly immunogenic antigens. Such multimerization platforms are generally based on icosahedral viruses and have led to vaccines given to millions of people. It is unclear whether synthetic protein nanoassemblies would show similar potency. Here we take the computationally designed porous dodecahedral i301 60-mer and rationally engineer this particle, giving a mutated i301 (mi3) with improved particle uniformity and stability. To simplify the conjugation of this nanoparticle, we employ a SpyCatcher fusion of mi3, such that an antigen of interest linked to the SpyTag peptide can spontaneously couple through isopeptide bond formation (Plug-and-Display). SpyCatcher-mi3 expressed solubly to high yields in Escherichia coli, giving more than 10-fold greater yield than a comparable phage-derived icosahedral nanoparticle, SpyCatcher-AP205. SpyCatcher-mi3 nanoparticles showed high stability to temperature, freeze-thaw, lyophilization, and storage over time. We demonstrate approximately 95% efficiency coupling to different transmission-blockin...Continue Reading

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Citations

Mar 16, 2019·Scientific Reports·Anne-Marie C AnderssonMark Howarth
Jul 23, 2019·Biotechnology and Bioengineering·Hansol KimSebyung Kang
Jan 1, 2020·Expert Review of Vaccines·Lasse NeukirchPeter Johannes Holst
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Mar 7, 2021·International Journal of Molecular Sciences·Que Dan NguyenTakafumi Ueno
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Jun 9, 2021·International Journal of Biological Macromolecules·Ze-Hui LiuFang He
Aug 10, 2021·Frontiers in Immunology·Ze-Hui LiuFang He
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Mar 6, 2019·ACS Nano·Yang XuNicholas Stephanopoulos
Aug 29, 2021·Pharmaceuticals·David S PeabodyBryce Chackerian
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Dec 24, 2021·Biomacromolecules·Md Shahadat HossainDavoud Mozhdehi
Jan 29, 2022·The Journal of Microbiology·Chulwoo KimSang-Uk Seo

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Datasets Mentioned

BETA
KU302810

Methods Mentioned

BETA
size-exclusion chromatography
dynamic light scattering
size-exclusion purification
transmission electron microscopy
enzyme-linked immunosorbent assay
ELISA
PCR
gel filtration
Assay
transfection

Software Mentioned

- Measure
ImageJ
SpyCatcher
BLAST
ImageLab
UniProt BLAST
SpyTag
PSI
Excel
PyMOL

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