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Elicitation of broadly protective sarbecovirus immunity by receptor-binding domain nanoparticle vaccines.
Walls, Alexandra C; Miranda, Marcos C; Pham, Minh N; Schäfer, Alexandra; Greaney, Allison; Arunachalam, Prabhu S; Navarro, Mary-Jane; Tortorici, M Alejandra; Rogers, Kenneth; O'Connor, Megan A; Shireff, Lisa; Ferrell, Douglas E; Brunette, Natalie; Kepl, Elizabeth; Bowen, John; Zepeda, Samantha K; Starr, Tyler; Hsieh, Ching-Lin; Fiala, Brooke; Wrenn, Samuel; Pettie, Deleah; Sydeman, Claire; Johnson, Max; Blackstone, Alyssa; Ravichandran, Rashmi; Ogohara, Cassandra; Carter, Lauren; Tilles, Sasha W; Rappuoli, Rino; O'Hagan, Derek T; Van Der Most, Robbert; Van Voorhis, Wesley C; McLellan, Jason S; Kleanthous, Harry; Sheahan, Timothy P; Fuller, Deborah H; Villinger, Francois; Bloom, Jesse; Pulendran, Bali; Baric, Ralph; King, Neil; Veesler, David.
Afiliación
  • Walls AC; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • Miranda MC; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • Pham MN; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
  • Schäfer A; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • Greaney A; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
  • Arunachalam PS; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
  • Navarro MJ; Basic Sciences and Computational Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
  • Tortorici MA; Department of Genome Sciences, University of Washington, Seattle, WA 98109, USA.
  • Rogers K; Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.
  • O'Connor MA; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • Shireff L; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • Ferrell DE; Institut Pasteur and CNRS UMR 3569, Unité de Virologie Structurale, Paris, France.
  • Brunette N; New Iberia Research Center and Department of Biology, University of Louisiana at Lafayette, New Iberia, LA, 70560 USA.
  • Kepl E; Washington National Primate Research Center, Seattle, WA 98121, USA.
  • Bowen J; Department of Microbiology, University of Washington, Seattle, WA 98195, USA.
  • Zepeda SK; New Iberia Research Center and Department of Biology, University of Louisiana at Lafayette, New Iberia, LA, 70560 USA.
  • Starr T; New Iberia Research Center and Department of Biology, University of Louisiana at Lafayette, New Iberia, LA, 70560 USA.
  • Hsieh CL; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • Fiala B; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
  • Wrenn S; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • Pettie D; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
  • Sydeman C; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • Johnson M; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • Blackstone A; Basic Sciences and Computational Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
  • Ravichandran R; Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.
  • Ogohara C; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • Carter L; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
  • Tilles SW; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • Rappuoli R; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
  • O'Hagan DT; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • Van Der Most R; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
  • Van Voorhis WC; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • McLellan JS; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
  • Kleanthous H; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • Sheahan TP; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
  • Fuller DH; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • Villinger F; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
  • Bloom J; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • Pulendran B; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
  • Baric R; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • King N; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
  • Veesler D; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
bioRxiv ; 2021 Mar 16.
Article en En | MEDLINE | ID: mdl-33758839
ABSTRACT
Understanding the ability of SARS-CoV-2 vaccine-elicited antibodies to neutralize and protect against emerging variants of concern and other sarbecoviruses is key for guiding vaccine development decisions and public health policies. We show that a clinical stage multivalent SARS-CoV-2 receptor-binding domain nanoparticle vaccine (SARS-CoV-2 RBD-NP) protects mice from SARS-CoV-2-induced disease after a single shot, indicating that the vaccine could allow dose-sparing. SARS-CoV-2 RBD-NP elicits high antibody titers in two non-human primate (NHP) models against multiple distinct RBD antigenic sites known to be recognized by neutralizing antibodies. We benchmarked NHP serum neutralizing activity elicited by RBD-NP against a lead prefusion-stabilized SARS-CoV-2 spike immunogen using a panel of single-residue spike mutants detected in clinical isolates as well as the B.1.1.7 and B.1.351 variants of concern. Polyclonal antibodies elicited by both vaccines are resilient to most RBD mutations tested, but the E484K substitution has similar negative consequences for neutralization, and exhibit modest but comparable neutralization breadth against distantly related sarbecoviruses. We demonstrate that mosaic and cocktail sarbecovirus RBD-NPs elicit broad sarbecovirus neutralizing activity, including against the SARS-CoV-2 B.1.351 variant, and protect mice against severe SARS-CoV challenge even in the absence of the SARS-CoV RBD in the vaccine. This study provides proof of principle that sarbecovirus RBD-NPs induce heterotypic protection and enables advancement of broadly protective sarbecovirus vaccines to the clinic.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: BioRxiv Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: BioRxiv Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos