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Self-assembling protein nanoparticles and virus like particles correctly display β-barrel from meningococcal factor H-binding protein through genetic fusion

Recombinant protein-based vaccines are a valid and safer alternative to traditional vaccines based on live-attenuated or killed pathogens. However, the immune response of subunit vaccines is generally lower compared to that elicited by traditional vaccines and usually requires the use of adjuvants....

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Autores principales: Cappelli, Luigia, Cinelli, Paolo, Giusti, Fabiola, Ferlenghi, Ilaria, Utrio-Lanfaloni, Sabrina, Wahome, Newton, Bottomley, Matthew James, Maione, Domenico, Cozzi, Roberta
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9480994/
https://www.ncbi.nlm.nih.gov/pubmed/36112575
http://dx.doi.org/10.1371/journal.pone.0273322
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author Cappelli, Luigia
Cinelli, Paolo
Giusti, Fabiola
Ferlenghi, Ilaria
Utrio-Lanfaloni, Sabrina
Wahome, Newton
Bottomley, Matthew James
Maione, Domenico
Cozzi, Roberta
author_facet Cappelli, Luigia
Cinelli, Paolo
Giusti, Fabiola
Ferlenghi, Ilaria
Utrio-Lanfaloni, Sabrina
Wahome, Newton
Bottomley, Matthew James
Maione, Domenico
Cozzi, Roberta
author_sort Cappelli, Luigia
collection PubMed
description Recombinant protein-based vaccines are a valid and safer alternative to traditional vaccines based on live-attenuated or killed pathogens. However, the immune response of subunit vaccines is generally lower compared to that elicited by traditional vaccines and usually requires the use of adjuvants. The use of self-assembling protein nanoparticles, as a platform for vaccine antigen presentation, is emerging as a promising approach to enhance the production of protective and functional antibodies. In this work we demonstrated the successful repetitive antigen display of the C-terminal β-barrel domain of factor H binding protein, derived from serogroup B Meningococcus on the surface of different self-assembling nanoparticles using genetic fusion. Six nanoparticle scaffolds were tested, including virus-like particles with different sizes, geometries, and physicochemical properties. Combining computational and structure-based rational design we were able generate antigen-fused scaffolds that closely aligned with three-dimensional structure predictions. The chimeric nanoparticles were produced as recombinant proteins in Escherichia coli and evaluated for solubility, stability, self-assembly, and antigen accessibility using a variety of biophysical methods. Several scaffolds were identified as being suitable for genetic fusion with the β-barrel from fHbp, including ferritin, a de novo designed aldolase from Thermotoga maritima, encapsulin, CP3 phage coat protein, and the Hepatitis B core antigen. In conclusion, a systematic screening of self-assembling nanoparticles has been applied for the repetitive surface display of a vaccine antigen. This work demonstrates the capacity of rational structure-based design to develop new chimeric nanoparticles and describes a strategy that can be utilized to discover new nanoparticle-based approaches in the search for vaccines against bacterial pathogens.
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spelling pubmed-94809942022-09-17 Self-assembling protein nanoparticles and virus like particles correctly display β-barrel from meningococcal factor H-binding protein through genetic fusion Cappelli, Luigia Cinelli, Paolo Giusti, Fabiola Ferlenghi, Ilaria Utrio-Lanfaloni, Sabrina Wahome, Newton Bottomley, Matthew James Maione, Domenico Cozzi, Roberta PLoS One Research Article Recombinant protein-based vaccines are a valid and safer alternative to traditional vaccines based on live-attenuated or killed pathogens. However, the immune response of subunit vaccines is generally lower compared to that elicited by traditional vaccines and usually requires the use of adjuvants. The use of self-assembling protein nanoparticles, as a platform for vaccine antigen presentation, is emerging as a promising approach to enhance the production of protective and functional antibodies. In this work we demonstrated the successful repetitive antigen display of the C-terminal β-barrel domain of factor H binding protein, derived from serogroup B Meningococcus on the surface of different self-assembling nanoparticles using genetic fusion. Six nanoparticle scaffolds were tested, including virus-like particles with different sizes, geometries, and physicochemical properties. Combining computational and structure-based rational design we were able generate antigen-fused scaffolds that closely aligned with three-dimensional structure predictions. The chimeric nanoparticles were produced as recombinant proteins in Escherichia coli and evaluated for solubility, stability, self-assembly, and antigen accessibility using a variety of biophysical methods. Several scaffolds were identified as being suitable for genetic fusion with the β-barrel from fHbp, including ferritin, a de novo designed aldolase from Thermotoga maritima, encapsulin, CP3 phage coat protein, and the Hepatitis B core antigen. In conclusion, a systematic screening of self-assembling nanoparticles has been applied for the repetitive surface display of a vaccine antigen. This work demonstrates the capacity of rational structure-based design to develop new chimeric nanoparticles and describes a strategy that can be utilized to discover new nanoparticle-based approaches in the search for vaccines against bacterial pathogens. Public Library of Science 2022-09-16 /pmc/articles/PMC9480994/ /pubmed/36112575 http://dx.doi.org/10.1371/journal.pone.0273322 Text en © 2022 Cappelli et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Cappelli, Luigia
Cinelli, Paolo
Giusti, Fabiola
Ferlenghi, Ilaria
Utrio-Lanfaloni, Sabrina
Wahome, Newton
Bottomley, Matthew James
Maione, Domenico
Cozzi, Roberta
Self-assembling protein nanoparticles and virus like particles correctly display β-barrel from meningococcal factor H-binding protein through genetic fusion
title Self-assembling protein nanoparticles and virus like particles correctly display β-barrel from meningococcal factor H-binding protein through genetic fusion
title_full Self-assembling protein nanoparticles and virus like particles correctly display β-barrel from meningococcal factor H-binding protein through genetic fusion
title_fullStr Self-assembling protein nanoparticles and virus like particles correctly display β-barrel from meningococcal factor H-binding protein through genetic fusion
title_full_unstemmed Self-assembling protein nanoparticles and virus like particles correctly display β-barrel from meningococcal factor H-binding protein through genetic fusion
title_short Self-assembling protein nanoparticles and virus like particles correctly display β-barrel from meningococcal factor H-binding protein through genetic fusion
title_sort self-assembling protein nanoparticles and virus like particles correctly display β-barrel from meningococcal factor h-binding protein through genetic fusion
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9480994/
https://www.ncbi.nlm.nih.gov/pubmed/36112575
http://dx.doi.org/10.1371/journal.pone.0273322
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