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

  1. David W Hawman  Is a corresponding author
  2. Kimberly Meade-White
  3. Jacob Archer
  4. Shanna S Leventhal
  5. Drew Wilson
  6. Carl Shaia
  7. Samantha Randall
  8. Amit P Khandhar
  9. Kyle Krieger
  10. Tien-Ying Hsiang
  11. Michael Gale Jr
  12. Peter Berglund
  13. Deborah Heydenburg Fuller
  14. Heinz Feldmann  Is a corresponding author
  15. Jesse Erasmus  Is a corresponding author
  1. National Institute of Allergy and Infectious Diseases, United States
  2. HDT Bio, United States
  3. University of Washington, United States
  4. 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

  1. David W Hawman

    Laboratory of Virology, National Institute of Allergy and Infectious Diseases, Hamilton, United States
    For correspondence
    david.hawman@nih.gov
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8233-8176
  2. Kimberly Meade-White

    Laboratory of Virology, National Institute of Allergy and Infectious Diseases, Hamilton, United States
    Competing interests
    No competing interests declared.
  3. Jacob Archer

    HDT Bio, Seattle, United States
    Competing interests
    Jacob Archer, is a consultant for InBios.
  4. Shanna S Leventhal

    Laboratory of Virology, National Institute of Allergy and Infectious Diseases, Hamilton, United States
    Competing interests
    No competing interests declared.
  5. Drew Wilson

    Laboratory of Virology, National Institute of Allergy and Infectious Diseases, Hamilton, United States
    Competing interests
    No competing interests declared.
  6. Carl Shaia

    Division of Intramural Research, National Institute of Allergy and Infectious Diseases, Hamilton, United States
    Competing interests
    No competing interests declared.
  7. Samantha Randall

    Department of Microbiology, University of Washington, Seattle, United States
    Competing interests
    No competing interests declared.
  8. Amit P Khandhar

    HDT Bio, Seattle, United States
    Competing interests
    Amit P Khandhar, has equity interest in HDT Bio. Is a co-inventors on U.S. patent application no. 62/993,307 Compositions and methods for delivery of RNA" pertaining to the LION formulation.".
  9. Kyle Krieger

    HDT Bio, Seattle, United States
    Competing interests
    No competing interests declared.
  10. Tien-Ying Hsiang

    Department of Immunology, The University of Washington, Seattle, United States
    Competing interests
    No competing interests declared.
  11. Michael Gale Jr

    Department of Immunology, University of Washington, Seattle, United States
    Competing interests
    Michael Gale, has equity interest in HDT Bio..
  12. Peter Berglund

    HDT Bio, Seattle, United States
    Competing interests
    Peter Berglund, has equity interest in HDT Bio. Is a consultant for Arcturus, Sensei, and Next Phase..
  13. Deborah Heydenburg Fuller

    Department of Microbiology, University of Washington, Seattle, United States
    Competing interests
    Deborah Heydenburg Fuller, has equity interest in HDT Bio. Is a consultant for Gerson Lehrman Group, Orlance, Abacus Bioscience, Neoleukin Therapeutics..
  14. Heinz Feldmann

    Laboratory of Virology, National Institute of Allergy and Infectious Diseases, Hamilton, United States
    For correspondence
    feldmannh@niaid.nih.gov
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9448-8227
  15. Jesse Erasmus

    HDT Bio, Seattle, United States
    For correspondence
    jesse.erasmus@hdt.bio
    Competing interests
    Jesse Erasmus, has equity interest in HDT Bio. Is a consultant for InBios. Is a co-inventors on U.S. patent application no. 62/993,307 Compositions and methods for delivery of RNA" pertaining to the LION formulation.".
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1612-2697

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.

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).

Reviewing Editor

  1. Tomohiro Kurosaki, Osaka University, Japan

Publication history

  1. Received: November 13, 2021
  2. Preprint posted: December 13, 2021 (view preprint)
  3. Accepted: February 17, 2022
  4. Accepted Manuscript published: February 22, 2022 (version 1)
  5. 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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  1. David W Hawman
  2. Kimberly Meade-White
  3. Jacob Archer
  4. Shanna S Leventhal
  5. Drew Wilson
  6. Carl Shaia
  7. Samantha Randall
  8. Amit P Khandhar
  9. Kyle Krieger
  10. Tien-Ying Hsiang
  11. Michael Gale Jr
  12. Peter Berglund
  13. Deborah Heydenburg Fuller
  14. Heinz Feldmann
  15. Jesse Erasmus
(2022)
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
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