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A safe, effective and adaptable live-attenuated SARS-CoV-2 vaccine to reduce disease and transmission using one-to-stop genome modifications.
Schön, Jacob; Barut, G Tuba; Trüeb, Bettina Salome; Halwe, Nico Joel; Berenguer Veiga, Inês; Kratzel, Annika; Ulrich, Lorenz; Kelly, Jenna N; Brügger, Melanie; Wylezich, Claudia; Taddeo, Adriano; Aguiar Moreira, Etori; Túrós, Demeter; Grau-Roma, Llorenç; Ahrens, Ann Kathrin; Schlottau, Kore; Britzke, Tobias; Breithaupt, Angele; Corleis, Björn; Kochmann, Jana; Oliveira Esteves, Blandina I; Almeida, Lea; Thomann, Lisa; Devisme, Christelle; Stalder, Hanspeter; Steiner, Silvio; Ochsenbein, Sarah; Schmied, Kimberly; Labroussaa, Fabien; Jores, Jörg; V'kovski, Philip; Cmiljanovic, Vladimir; Alves, Marco P; Benarafa, Charaf; Ebert, Nadine; Hoffmann, Donata; Beer, Martin; Thiel, Volker.
Affiliation
  • Schön J; Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany.
  • Barut GT; Institute of Virology and Immunology, Bern and Mittelhäusern, Bern, Switzerland.
  • Trüeb BS; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
  • Halwe NJ; Institute of Virology and Immunology, Bern and Mittelhäusern, Bern, Switzerland.
  • Berenguer Veiga I; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
  • Kratzel A; Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany.
  • Ulrich L; Institute of Virology and Immunology, Bern and Mittelhäusern, Bern, Switzerland.
  • Kelly JN; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
  • Brügger M; Institute of Virology and Immunology, Bern and Mittelhäusern, Bern, Switzerland.
  • Wylezich C; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
  • Taddeo A; Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany.
  • Aguiar Moreira E; Institute of Virology and Immunology, Bern and Mittelhäusern, Bern, Switzerland.
  • Túrós D; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
  • Grau-Roma L; Multidisciplinary Center for Infectious Diseases, University of Bern, Bern, Switzerland.
  • Ahrens AK; European Virus Bioinformatics Center, Jena, Germany.
  • Schlottau K; Institute of Virology and Immunology, Bern and Mittelhäusern, Bern, Switzerland.
  • Britzke T; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
  • Breithaupt A; Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany.
  • Corleis B; Department of Experimental Animal Facilities and Biorisk Management, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany.
  • Kochmann J; Institute of Virology and Immunology, Bern and Mittelhäusern, Bern, Switzerland.
  • Oliveira Esteves BI; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
  • Almeida L; Institute of Virology and Immunology, Bern and Mittelhäusern, Bern, Switzerland.
  • Thomann L; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
  • Devisme C; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
  • Stalder H; Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland.
  • Steiner S; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
  • Ochsenbein S; Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany.
  • Schmied K; Institute of Diagnostic Virology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany.
  • Labroussaa F; Department of Experimental Animal Facilities and Biorisk Management, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany.
  • Jores J; Department of Experimental Animal Facilities and Biorisk Management, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany.
  • V'kovski P; Institute of Immunology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany.
  • Cmiljanovic V; Institute of Immunology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany.
  • Alves MP; Institute of Virology and Immunology, Bern and Mittelhäusern, Bern, Switzerland.
  • Benarafa C; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
  • Ebert N; Institute of Virology and Immunology, Bern and Mittelhäusern, Bern, Switzerland.
  • Hoffmann D; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
  • Beer M; Institute of Virology and Immunology, Bern and Mittelhäusern, Bern, Switzerland.
  • Thiel V; Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Bern, Switzerland.
Nat Microbiol ; 2024 Jul 12.
Article in En | MEDLINE | ID: mdl-38997518
ABSTRACT
Approved vaccines are effective against severe COVID-19, but broader immunity is needed against new variants and transmission. Therefore, we developed genome-modified live-attenuated vaccines (LAV) by recoding the SARS-CoV-2 genome, including 'one-to-stop' (OTS) codons, disabling Nsp1 translational repression and removing ORF6, 7ab and 8 to boost host immune responses, as well as the spike polybasic cleavage site to optimize the safety profile. The resulting OTS-modified SARS-CoV-2 LAVs, designated as OTS-206 and OTS-228, are genetically stable and can be intranasally administered, while being adjustable and sustainable regarding the level of attenuation. OTS-228 exhibits an optimal safety profile in preclinical animal models, with no side effects or detectable transmission. A single-dose vaccination induces a sterilizing immunity in vivo against homologous WT SARS-CoV-2 challenge infection and a broad protection against Omicron BA.2, BA.5 and XBB.1.5, with reduced transmission. Finally, this promising LAV approach could be applicable to other emerging viruses.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Nat Microbiol Year: 2024 Type: Article Affiliation country: Germany
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Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Nat Microbiol Year: 2024 Type: Article Affiliation country: Germany