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Low-dose bivalent mRNA vaccine is highly effective against different SARS-CoV-2 variants in a transgenic mouse model
Björn Corleis; Donata Hoffmann; Susanne Rauch; Charlie Fricke; Nicole Roth; Janina Gergen; Kristina Kovacikova; Kore Schlottau; Nico Joel Halwe; Lorenz Ulrich; Jacob Schön; Kerstin Wernike; Marek Widera; Sandra Ciesek; Stefan Otto Mueller; Thomas C Mettenleiter; Benjamin Petsch; Martin Beer; Anca Dorhoi.
Afiliación
  • Björn Corleis; Institute of Immunology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany
  • Donata Hoffmann; Friedrich-Loeffler-Institut, Institute of diagnostic virology
  • Susanne Rauch; CureVac AG, Tübingen, Germany
  • Charlie Fricke; Friedrich-Loeffler-Institut; Institute of Immunology
  • Nicole Roth; CureVac AG, Tübingen, Germany
  • Janina Gergen; CureVac AG, Tübingen, Germany
  • Kristina Kovacikova; CureVac AG, Tübingen, Germany
  • Kore Schlottau; Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany
  • Nico Joel Halwe; Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany
  • Lorenz Ulrich; Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany
  • Jacob Schön; Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany
  • Kerstin Wernike; Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany
  • Marek Widera; Institut für Med. Virologie, Universitätsklinikum Frankfurt (AöR), Paul-Ehrlich-Str.40, 60596 Frankfurt am Main
  • Sandra Ciesek; Institute of Medical Virology, University Hospital, Goethe University; German Center for Infection Research (DZIF), 38124 Braunschweig; Branch Translational Med
  • Stefan Otto Mueller; CureVac AG, Tübingen, Germany
  • Thomas C Mettenleiter; Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany
  • Benjamin Petsch; CureVac AG, Tübingen, Germany
  • Martin Beer; Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany
  • Anca Dorhoi; Institute of Immunology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany
Preprint en En | PREPRINT-BIORXIV | ID: ppbiorxiv-485440
ABSTRACT
Combining optimized spike (S) protein-encoding mRNA vaccines to target multiple SARS-CoV-2 variants could improve COVID-19 control. We compared monovalent and bivalent mRNA vaccines encoding B.1.351 (Beta) and/or B.1.617.2 (Delta) SARS-CoV-2 S-protein, primarily in a transgenic mouse model and a Wistar rat model. The low-dose bivalent mRNA vaccine contained half the mRNA of each respective monovalent vaccine, but induced comparable neutralizing antibody titres, enrichment of lung-resident memory CD8+ T cells, specific CD4+ and CD8+ responses, and fully protected transgenic mice from SARS-CoV-2 lethality. The bivalent mRNA vaccine significantly reduced viral replication in both Beta- and Delta-challenged mice. Sera from bivalent mRNA vaccine immunized Wistar rats also contained neutralizing antibodies against the B.1.1.529 (Omicron BA.1) variant. These data suggest that low-dose and fit-for-purpose multivalent mRNA vaccines encoding distinct S-proteins is a feasible approach for increasing the potency of vaccines against emerging and co-circulating SARS-CoV-2 variants.
Licencia
cc_by_nc_nd
Texto completo: 1 Colección: 09-preprints Base de datos: PREPRINT-BIORXIV Tipo de estudio: Experimental_studies Idioma: En Año: 2022 Tipo del documento: Preprint
Texto completo: 1 Colección: 09-preprints Base de datos: PREPRINT-BIORXIV Tipo de estudio: Experimental_studies Idioma: En Año: 2022 Tipo del documento: Preprint