SARS-CoV2 variant-specific replicating RNA vaccines protect from disease and pathology and reduce viral shedding following challenge with heterologous SARS-CoV2 variants of concern
- National Institute of Allergy and Infectious Diseases, United States
- HDT Bio, United States
- University of Washington, United States
- The University of Washington, United States
Abstract
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 (VoC) 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.
Data availability
All data generated or analyzed during this study are included in the figures and supporting files
Article and author information
Author details
Funding
National Institute of Allergy and Infectious Diseases
- Michael Gale Jr
- Jesse Erasmus
Division of Intramural Research, National Institute of Allergy and Infectious Diseases
- David W Hawman
- Kimberly Meade-White
- Shanna S Leventhal
- Drew Wilson
- Carl Shaia
- Heinz Feldmann
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Tomohiro Kurosaki, Osaka University, Japan
Ethics
Animal experimentation: Animal experiments were approved by the corresponding institutional animal care and use committee and performed by experienced personnel under veterinary oversight (Protocol #2020-63).
Version history
- Received: November 13, 2021
- Preprint posted: December 13, 2021 (view preprint)
- Accepted: February 17, 2022
- Accepted Manuscript published: February 22, 2022 (version 1)
- Version of Record published: April 5, 2022 (version 2)
Copyright
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.
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SARS-CoV2 variant-specific replicating RNA vaccines protect from disease and pathology and reduce viral shedding following challenge with heterologous SARS-CoV2 variants of concern
eLife 11:e75537.
https://doi.org/10.7554/eLife.75537
Further reading
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