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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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2022-02-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/75537 |
| _version_ | 1797998329071665152 |
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| author | David W Hawman Kimberly Meade-White Jacob Archer Shanna S Leventhal Drew Wilson Carl Shaia Samantha Randall Amit P Khandhar Kyle Krieger Tien-Ying Hsiang Michael Gale Peter Berglund Deborah Heydenburg Fuller Heinz Feldmann Jesse H Erasmus |
| author_facet | David W Hawman Kimberly Meade-White Jacob Archer Shanna S Leventhal Drew Wilson Carl Shaia Samantha Randall Amit P Khandhar Kyle Krieger Tien-Ying Hsiang Michael Gale Peter Berglund Deborah Heydenburg Fuller Heinz Feldmann Jesse H Erasmus |
| author_sort | David W Hawman |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-11T10:46:55Z |
| format | Article |
| id | doaj.art-90febf2692524714945d906eb9c6e393 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T10:46:55Z |
| publishDate | 2022-02-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-90febf2692524714945d906eb9c6e3932022-12-22T04:29:02ZengeLife Sciences Publications LtdeLife2050-084X2022-02-011110.7554/eLife.75537SARS-CoV2 variant-specific replicating RNA vaccines protect from disease following challenge with heterologous variants of concernDavid W Hawman0https://orcid.org/0000-0001-8233-8176Kimberly Meade-White1Jacob Archer2Shanna S Leventhal3Drew Wilson4Carl Shaia5Samantha Randall6Amit P Khandhar7Kyle Krieger8Tien-Ying Hsiang9Michael Gale10Peter Berglund11Deborah Heydenburg Fuller12Heinz Feldmann13https://orcid.org/0000-0001-9448-8227Jesse H Erasmus14https://orcid.org/0000-0003-1612-2697Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, United StatesLaboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, United StatesHDT Bio, Seattle, United StatesLaboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, United StatesLaboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, United StatesRocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, United StatesDepartment of Microbiology, University of Washington School of Medicine, Seattle, United StatesHDT Bio, Seattle, United StatesHDT Bio, Seattle, United StatesCenter for Innate Immunity and Immune Disease, Department of Immunology, University of Washington School of Medicine, Seattle, United StatesCenter for Innate Immunity and Immune Disease, Department of Immunology, University of Washington School of Medicine, Seattle, United StatesHDT Bio, Seattle, United StatesDepartment of Microbiology, University of Washington School of Medicine, Seattle, United StatesLaboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, United StatesHDT Bio, Seattle, United States; Department of Microbiology, University of Washington School of Medicine, Seattle, United StatesDespite 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.https://elifesciences.org/articles/75537hamsterCOVID-19vaccineRNA vaccinereplicon |
| spellingShingle | David W Hawman Kimberly Meade-White Jacob Archer Shanna S Leventhal Drew Wilson Carl Shaia Samantha Randall Amit P Khandhar Kyle Krieger Tien-Ying Hsiang Michael Gale Peter Berglund Deborah Heydenburg Fuller Heinz Feldmann Jesse H Erasmus SARS-CoV2 variant-specific replicating RNA vaccines protect from disease following challenge with heterologous variants of concern eLife hamster COVID-19 vaccine RNA vaccine replicon |
| 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 | hamster COVID-19 vaccine RNA vaccine replicon |
| url | https://elifesciences.org/articles/75537 |
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