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SARS-CoV2 variant-specific replicating RNA vaccines protect from disease following challenge with heterologous variants of concern

Despite mass public health efforts, the SARS-CoV2 pandemic continues as of late 2021 with resurgent case numbers in many parts of the world. The emergence of SARS-CoV2 variants of concern (VoCs) and evidence that existing vaccines that were designed to protect from the original strains of SARS-CoV-2...

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Autores principales: Hawman, David W, Meade-White, Kimberly, Archer, Jacob, Leventhal, Shanna S, Wilson, Drew, Shaia, Carl, Randall, Samantha, Khandhar, Amit P, Krieger, Kyle, Hsiang, Tien-Ying, Gale, Michael, Berglund, Peter, Fuller, Deborah Heydenburg, Feldmann, Heinz, Erasmus, Jesse H
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8983041/
https://www.ncbi.nlm.nih.gov/pubmed/35191378
http://dx.doi.org/10.7554/eLife.75537
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author Hawman, David W
Meade-White, Kimberly
Archer, Jacob
Leventhal, Shanna S
Wilson, Drew
Shaia, Carl
Randall, Samantha
Khandhar, Amit P
Krieger, Kyle
Hsiang, Tien-Ying
Gale, Michael
Berglund, Peter
Fuller, Deborah Heydenburg
Feldmann, Heinz
Erasmus, Jesse H
author_facet Hawman, David W
Meade-White, Kimberly
Archer, Jacob
Leventhal, Shanna S
Wilson, Drew
Shaia, Carl
Randall, Samantha
Khandhar, Amit P
Krieger, Kyle
Hsiang, Tien-Ying
Gale, Michael
Berglund, Peter
Fuller, Deborah Heydenburg
Feldmann, Heinz
Erasmus, Jesse H
author_sort Hawman, David W
collection PubMed
description Despite mass public health efforts, the SARS-CoV2 pandemic continues as of late 2021 with resurgent case numbers in many parts of the world. The emergence of SARS-CoV2 variants of concern (VoCs) and evidence that existing vaccines that were designed to protect from the original strains of SARS-CoV-2 may have reduced potency for protection from infection against these VoC is driving continued development of second-generation vaccines that can protect against multiple VoC. In this report, we evaluated an alphavirus-based replicating RNA vaccine expressing Spike proteins from the original SARS-CoV-2 Alpha strain and recent VoCs delivered in vivo via a lipid inorganic nanoparticle. Vaccination of both mice and Syrian Golden hamsters showed that vaccination induced potent neutralizing titers against each homologous VoC but reduced neutralization against heterologous challenges. Vaccinated hamsters challenged with homologous SARS-CoV2 variants exhibited complete protection from infection. In addition, vaccinated hamsters challenged with heterologous SARS-CoV-2 variants exhibited significantly reduced shedding of infectious virus. Our data demonstrate that this vaccine platform can be updated to target emergent VoCs, elicits significant protective immunity against SARS-CoV2 variants and supports continued development of this platform.
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spelling pubmed-89830412022-04-06 SARS-CoV2 variant-specific replicating RNA vaccines protect from disease following challenge with heterologous variants of concern Hawman, David W Meade-White, Kimberly Archer, Jacob Leventhal, Shanna S Wilson, Drew Shaia, Carl Randall, Samantha Khandhar, Amit P Krieger, Kyle Hsiang, Tien-Ying Gale, Michael Berglund, Peter Fuller, Deborah Heydenburg Feldmann, Heinz Erasmus, Jesse H eLife Immunology and Inflammation Despite mass public health efforts, the SARS-CoV2 pandemic continues as of late 2021 with resurgent case numbers in many parts of the world. The emergence of SARS-CoV2 variants of concern (VoCs) and evidence that existing vaccines that were designed to protect from the original strains of SARS-CoV-2 may have reduced potency for protection from infection against these VoC is driving continued development of second-generation vaccines that can protect against multiple VoC. In this report, we evaluated an alphavirus-based replicating RNA vaccine expressing Spike proteins from the original SARS-CoV-2 Alpha strain and recent VoCs delivered in vivo via a lipid inorganic nanoparticle. Vaccination of both mice and Syrian Golden hamsters showed that vaccination induced potent neutralizing titers against each homologous VoC but reduced neutralization against heterologous challenges. Vaccinated hamsters challenged with homologous SARS-CoV2 variants exhibited complete protection from infection. In addition, vaccinated hamsters challenged with heterologous SARS-CoV-2 variants exhibited significantly reduced shedding of infectious virus. Our data demonstrate that this vaccine platform can be updated to target emergent VoCs, elicits significant protective immunity against SARS-CoV2 variants and supports continued development of this platform. eLife Sciences Publications, Ltd 2022-02-22 /pmc/articles/PMC8983041/ /pubmed/35191378 http://dx.doi.org/10.7554/eLife.75537 Text en https://creativecommons.org/publicdomain/zero/1.0/This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication (https://creativecommons.org/publicdomain/zero/1.0/) .
spellingShingle Immunology and Inflammation
Hawman, David W
Meade-White, Kimberly
Archer, Jacob
Leventhal, Shanna S
Wilson, Drew
Shaia, Carl
Randall, Samantha
Khandhar, Amit P
Krieger, Kyle
Hsiang, Tien-Ying
Gale, Michael
Berglund, Peter
Fuller, Deborah Heydenburg
Feldmann, Heinz
Erasmus, Jesse H
SARS-CoV2 variant-specific replicating RNA vaccines protect from disease following challenge with heterologous variants of concern
title SARS-CoV2 variant-specific replicating RNA vaccines protect from disease following challenge with heterologous variants of concern
title_full SARS-CoV2 variant-specific replicating RNA vaccines protect from disease following challenge with heterologous variants of concern
title_fullStr SARS-CoV2 variant-specific replicating RNA vaccines protect from disease following challenge with heterologous variants of concern
title_full_unstemmed SARS-CoV2 variant-specific replicating RNA vaccines protect from disease following challenge with heterologous variants of concern
title_short SARS-CoV2 variant-specific replicating RNA vaccines protect from disease following challenge with heterologous variants of concern
title_sort sars-cov2 variant-specific replicating rna vaccines protect from disease following challenge with heterologous variants of concern
topic Immunology and Inflammation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8983041/
https://www.ncbi.nlm.nih.gov/pubmed/35191378
http://dx.doi.org/10.7554/eLife.75537
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