CVnCoV and CV2CoV protect human ACE2 transgenic mice from ancestral B BavPat1 and emerging B.1.351 SARS-CoV-2.

Donata Hoffmann, Björn Corleis, Susanne Rauch, Nicole Roth, Janine Mühe, Nico Joel Halwe, Lorenz Ulrich, Charlie Fricke, Jacob Schön, Anna Kraft, Angele Breithaupt, Kerstin Wernike, Anna Michelitsch, Franziska Sick, Claudia Wylezich, Bernd Hoffmann, Moritz Thran, Andreas Thess, Stefan O Mueller, Thomas C Mettenleiter, Benjamin Petsch, Anca Dorhoi, Martin Beer
Author Information
  1. Donata Hoffmann: Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany. ORCID
  2. Björn Corleis: Institute of Immunology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany.
  3. Susanne Rauch: CureVac AG, Tübingen, Germany.
  4. Nicole Roth: CureVac AG, Tübingen, Germany.
  5. Janine Mühe: CureVac AG, Tübingen, Germany.
  6. Nico Joel Halwe: Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany. ORCID
  7. Lorenz Ulrich: Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany. ORCID
  8. Charlie Fricke: Institute of Immunology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany. ORCID
  9. Jacob Schön: Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany.
  10. Anna Kraft: Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany. ORCID
  11. Angele Breithaupt: Department of Experimental Animal Facilities and Biorisk Management, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany. ORCID
  12. Kerstin Wernike: Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany. ORCID
  13. Anna Michelitsch: Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany. ORCID
  14. Franziska Sick: Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany.
  15. Claudia Wylezich: Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany. ORCID
  16. Bernd Hoffmann: Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany.
  17. Moritz Thran: CureVac AG, Tübingen, Germany.
  18. Andreas Thess: CureVac AG, Tübingen, Germany. ORCID
  19. Stefan O Mueller: CureVac AG, Tübingen, Germany.
  20. Thomas C Mettenleiter: Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Greifswald-Insel Riems, Germany.
  21. Benjamin Petsch: CureVac AG, Tübingen, Germany.
  22. Anca Dorhoi: Institute of Immunology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany. anca.dorhoi@fli.de. ORCID
  23. Martin Beer: Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany. martin.beer@fli.de. ORCID

Abstract

The ongoing SARS-CoV-2 pandemic necessitates the fast development of vaccines. Recently, viral mutants termed variants of concern (VOC) which may escape host immunity have emerged. The efficacy of spike encoding mRNA vaccines (CVnCoV and CV2CoV) against the ancestral strain and the VOC B.1.351 was tested in a K18-hACE2 transgenic mouse model. Naive mice and mice immunized with a formalin-inactivated SARS-CoV-2 preparation were used as controls. mRNA-immunized mice develop elevated SARS-CoV-2 RBD-specific antibody and neutralization titers which are readily detectable, but significantly reduced against VOC B.1.351. The mRNA vaccines fully protect from disease and mortality caused by either viral strain. SARS-CoV-2 remains undetected in swabs, lung, or brain in these groups. Despite lower neutralizing antibody titers compared to the ancestral strain BavPat1, CVnCoV and CV2CoV show complete disease protection against the novel VOC B.1.351 in our studies.

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Grants

  1. 01KI20703/Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research)

MeSH Term

Angiotensin-Converting Enzyme 2
Animals
Antibodies, Neutralizing
Antibodies, Viral
COVID-19
COVID-19 Vaccines
Cell Line
Chlorocebus aethiops
Genome, Viral
Humans
Mice
Mice, Transgenic
SARS-CoV-2
Spike Glycoprotein, Coronavirus
Vero Cells

Chemicals

Antibodies, Neutralizing
Antibodies, Viral
COVID-19 Vaccines
Spike Glycoprotein, Coronavirus
spike protein, SARS-CoV-2
ACE2 protein, human
Angiotensin-Converting Enzyme 2