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Engineering a Rugged Nanoscaffold To Enhance Plug-and-Display Vaccination
[Image: see text] 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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American
Chemical Society
2018
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6158681/ https://www.ncbi.nlm.nih.gov/pubmed/30028591 http://dx.doi.org/10.1021/acsnano.8b02805 |
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author | Bruun, Theodora U. J. Andersson, Anne-Marie C. Draper, Simon J. Howarth, Mark |
author_facet | Bruun, Theodora U. J. Andersson, Anne-Marie C. Draper, Simon J. Howarth, Mark |
author_sort | Bruun, Theodora U. J. |
collection | PubMed |
description | [Image: see text] 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-blocking and blood-stage malaria antigens. Plasmodium falciparum CyRPA was conjugated to SpyCatcher-mi3 nanoparticles and elicited a high avidity antibody response, comparable to phage-derived virus-like particles despite their higher valency and RNA cargo. The simple production, precise derivatization, and exceptional ruggedness of this nanoscaffold should facilitate broad application for nanobiotechnology and vaccine development. |
format | Online Article Text |
id | pubmed-6158681 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | American
Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-61586812018-09-28 Engineering a Rugged Nanoscaffold To Enhance Plug-and-Display Vaccination Bruun, Theodora U. J. Andersson, Anne-Marie C. Draper, Simon J. Howarth, Mark ACS Nano [Image: see text] 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-blocking and blood-stage malaria antigens. Plasmodium falciparum CyRPA was conjugated to SpyCatcher-mi3 nanoparticles and elicited a high avidity antibody response, comparable to phage-derived virus-like particles despite their higher valency and RNA cargo. The simple production, precise derivatization, and exceptional ruggedness of this nanoscaffold should facilitate broad application for nanobiotechnology and vaccine development. American Chemical Society 2018-07-20 2018-09-25 /pmc/articles/PMC6158681/ /pubmed/30028591 http://dx.doi.org/10.1021/acsnano.8b02805 Text en Copyright © 2018 American Chemical Society This is an open access article published under a Creative Commons Attribution (CC-BY) License (http://pubs.acs.org/page/policy/authorchoice_ccby_termsofuse.html) , which permits unrestricted use, distribution and reproduction in any medium, provided the author and source are cited. |
spellingShingle | Bruun, Theodora U. J. Andersson, Anne-Marie C. Draper, Simon J. Howarth, Mark Engineering a Rugged Nanoscaffold To Enhance Plug-and-Display Vaccination |
title | Engineering a Rugged Nanoscaffold
To Enhance Plug-and-Display
Vaccination |
title_full | Engineering a Rugged Nanoscaffold
To Enhance Plug-and-Display
Vaccination |
title_fullStr | Engineering a Rugged Nanoscaffold
To Enhance Plug-and-Display
Vaccination |
title_full_unstemmed | Engineering a Rugged Nanoscaffold
To Enhance Plug-and-Display
Vaccination |
title_short | Engineering a Rugged Nanoscaffold
To Enhance Plug-and-Display
Vaccination |
title_sort | engineering a rugged nanoscaffold
to enhance plug-and-display
vaccination |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6158681/ https://www.ncbi.nlm.nih.gov/pubmed/30028591 http://dx.doi.org/10.1021/acsnano.8b02805 |
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