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A Nanoscaffolded Spike-RBD Vaccine Provides Protection against SARS-CoV-2 with Minimal Anti-Scaffold Response
The response of the adaptive immune system is augmented by multimeric presentation of a specific antigen, resembling viral particles. Several vaccines have been designed based on natural or designed protein scaffolds, which exhibited a potent adaptive immune response to antigens; however, antibodies...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146944/ https://www.ncbi.nlm.nih.gov/pubmed/33925446 http://dx.doi.org/10.3390/vaccines9050431 |
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author | Lainšček, Duško Fink, Tina Forstnerič, Vida Hafner-Bratkovič, Iva Orehek, Sara Strmšek, Žiga Manček-Keber, Mateja Pečan, Peter Esih, Hana Malenšek, Špela Aupič, Jana Dekleva, Petra Plaper, Tjaša Vidmar, Sara Kadunc, Lucija Benčina, Mojca Omersa, Neža Anderluh, Gregor Pojer, Florence Lau, Kelvin Hacker, David Correia, Bruno E. Peterhoff, David Wagner, Ralf Bergant, Valter Herrmann, Alexander Pichlmair, Andreas Jerala, Roman |
author_facet | Lainšček, Duško Fink, Tina Forstnerič, Vida Hafner-Bratkovič, Iva Orehek, Sara Strmšek, Žiga Manček-Keber, Mateja Pečan, Peter Esih, Hana Malenšek, Špela Aupič, Jana Dekleva, Petra Plaper, Tjaša Vidmar, Sara Kadunc, Lucija Benčina, Mojca Omersa, Neža Anderluh, Gregor Pojer, Florence Lau, Kelvin Hacker, David Correia, Bruno E. Peterhoff, David Wagner, Ralf Bergant, Valter Herrmann, Alexander Pichlmair, Andreas Jerala, Roman |
author_sort | Lainšček, Duško |
collection | PubMed |
description | The response of the adaptive immune system is augmented by multimeric presentation of a specific antigen, resembling viral particles. Several vaccines have been designed based on natural or designed protein scaffolds, which exhibited a potent adaptive immune response to antigens; however, antibodies are also generated against the scaffold, which may impair subsequent vaccination. In order to compare polypeptide scaffolds of different size and oligomerization state with respect to their efficiency, including anti-scaffold immunity, we compared several strategies of presentation of the RBD domain of the SARS-CoV-2 spike protein, an antigen aiming to generate neutralizing antibodies. A comparison of several genetic fusions of RBD to different nanoscaffolding domains (foldon, ferritin, lumazine synthase, and β-annulus peptide) delivered as DNA plasmids demonstrated a strongly augmented immune response, with high titers of neutralizing antibodies and a robust T-cell response in mice. Antibody titers and virus neutralization were most potently enhanced by fusion to the small β-annulus peptide scaffold, which itself triggered a minimal response in contrast to larger scaffolds. The β-annulus fused RBD protein increased residence in lymph nodes and triggered the most potent viral neutralization in immunization by a recombinant protein. Results of the study support the use of a nanoscaffolding platform using the β-annulus peptide for vaccine design. |
format | Online Article Text |
id | pubmed-8146944 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-81469442021-05-26 A Nanoscaffolded Spike-RBD Vaccine Provides Protection against SARS-CoV-2 with Minimal Anti-Scaffold Response Lainšček, Duško Fink, Tina Forstnerič, Vida Hafner-Bratkovič, Iva Orehek, Sara Strmšek, Žiga Manček-Keber, Mateja Pečan, Peter Esih, Hana Malenšek, Špela Aupič, Jana Dekleva, Petra Plaper, Tjaša Vidmar, Sara Kadunc, Lucija Benčina, Mojca Omersa, Neža Anderluh, Gregor Pojer, Florence Lau, Kelvin Hacker, David Correia, Bruno E. Peterhoff, David Wagner, Ralf Bergant, Valter Herrmann, Alexander Pichlmair, Andreas Jerala, Roman Vaccines (Basel) Article The response of the adaptive immune system is augmented by multimeric presentation of a specific antigen, resembling viral particles. Several vaccines have been designed based on natural or designed protein scaffolds, which exhibited a potent adaptive immune response to antigens; however, antibodies are also generated against the scaffold, which may impair subsequent vaccination. In order to compare polypeptide scaffolds of different size and oligomerization state with respect to their efficiency, including anti-scaffold immunity, we compared several strategies of presentation of the RBD domain of the SARS-CoV-2 spike protein, an antigen aiming to generate neutralizing antibodies. A comparison of several genetic fusions of RBD to different nanoscaffolding domains (foldon, ferritin, lumazine synthase, and β-annulus peptide) delivered as DNA plasmids demonstrated a strongly augmented immune response, with high titers of neutralizing antibodies and a robust T-cell response in mice. Antibody titers and virus neutralization were most potently enhanced by fusion to the small β-annulus peptide scaffold, which itself triggered a minimal response in contrast to larger scaffolds. The β-annulus fused RBD protein increased residence in lymph nodes and triggered the most potent viral neutralization in immunization by a recombinant protein. Results of the study support the use of a nanoscaffolding platform using the β-annulus peptide for vaccine design. MDPI 2021-04-27 /pmc/articles/PMC8146944/ /pubmed/33925446 http://dx.doi.org/10.3390/vaccines9050431 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Lainšček, Duško Fink, Tina Forstnerič, Vida Hafner-Bratkovič, Iva Orehek, Sara Strmšek, Žiga Manček-Keber, Mateja Pečan, Peter Esih, Hana Malenšek, Špela Aupič, Jana Dekleva, Petra Plaper, Tjaša Vidmar, Sara Kadunc, Lucija Benčina, Mojca Omersa, Neža Anderluh, Gregor Pojer, Florence Lau, Kelvin Hacker, David Correia, Bruno E. Peterhoff, David Wagner, Ralf Bergant, Valter Herrmann, Alexander Pichlmair, Andreas Jerala, Roman A Nanoscaffolded Spike-RBD Vaccine Provides Protection against SARS-CoV-2 with Minimal Anti-Scaffold Response |
title | A Nanoscaffolded Spike-RBD Vaccine Provides Protection against SARS-CoV-2 with Minimal Anti-Scaffold Response |
title_full | A Nanoscaffolded Spike-RBD Vaccine Provides Protection against SARS-CoV-2 with Minimal Anti-Scaffold Response |
title_fullStr | A Nanoscaffolded Spike-RBD Vaccine Provides Protection against SARS-CoV-2 with Minimal Anti-Scaffold Response |
title_full_unstemmed | A Nanoscaffolded Spike-RBD Vaccine Provides Protection against SARS-CoV-2 with Minimal Anti-Scaffold Response |
title_short | A Nanoscaffolded Spike-RBD Vaccine Provides Protection against SARS-CoV-2 with Minimal Anti-Scaffold Response |
title_sort | nanoscaffolded spike-rbd vaccine provides protection against sars-cov-2 with minimal anti-scaffold response |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8146944/ https://www.ncbi.nlm.nih.gov/pubmed/33925446 http://dx.doi.org/10.3390/vaccines9050431 |
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