SARS-CoV2 variant-specific replicating RNA vaccines protect from disease following challenge with heterologous variants of concern
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- David W Hawman
- Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories
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- Kimberly Meade-White
- Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories
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- Jacob Archer
- HDT Bio
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- Shanna S Leventhal
- Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories
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- Drew Wilson
- Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories
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- Carl Shaia
- Rocky Mountain Veterinary Branch, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories
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- Samantha Randall
- Department of Microbiology, University of Washington School of Medicine
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- Amit P Khandhar
- HDT Bio
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- Kyle Krieger
- HDT Bio
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- Tien-Ying Hsiang
- Center for Innate Immunity and Immune Disease, Department of Immunology, University of Washington School of Medicine
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- Michael Gale
- Center for Innate Immunity and Immune Disease, Department of Immunology, University of Washington School of Medicine
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- Peter Berglund
- HDT Bio
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- Deborah Heydenburg Fuller
- Department of Microbiology, University of Washington School of Medicine
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- Heinz Feldmann
- Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories
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- Jesse H Erasmus
- HDT Bio
説明
<jats:p>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.</jats:p>
収録刊行物
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- eLife
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eLife 11 2022-02-22
eLife Sciences Publications, Ltd
