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Elicitation of broadly protective sarbecovirus immunity by receptor-binding domain nanoparticle vaccines.
Walls, Alexandra C; Miranda, Marcos C; Schäfer, Alexandra; Pham, Minh N; Greaney, Allison; Arunachalam, Prabhu S; Navarro, Mary-Jane; Tortorici, M Alejandra; Rogers, Kenneth; O'Connor, Megan A; Shirreff, Lisa; Ferrell, Douglas E; Bowen, John; Brunette, Natalie; Kepl, Elizabeth; Zepeda, Samantha K; Starr, Tyler; Hsieh, Ching-Lin; Fiala, Brooke; Wrenn, Samuel; Pettie, Deleah; Sydeman, Claire; Sprouse, Kaitlin R; Johnson, Max; Blackstone, Alyssa; Ravichandran, Rashmi; Ogohara, Cassandra; Carter, Lauren; Tilles, Sasha W; Rappuoli, Rino; Leist, Sarah R; Martinez, David R; Clark, Matthew; Tisch, Roland; O'Hagan, Derek T; Van Der Most, Robbert; Van Voorhis, Wesley C; Corti, Davide; McLellan, Jason S; Kleanthous, Harry; Sheahan, Timothy P; Smith, Kelly D; Fuller, Deborah H; Villinger, Francois; Bloom, Jesse; Pulendran, Bali; Baric, Ralph S; King, Neil P; Veesler, David.
  • Walls AC; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • Miranda MC; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
  • Schäfer A; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
  • Pham MN; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
  • Greaney A; Basic Sciences and Computational Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Department of Genome Sciences, University of Washington, Seattle, WA 98109, USA.
  • Arunachalam PS; Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.
  • Navarro MJ; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • Tortorici MA; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institut Pasteur and CNRS UMR 3569, Unité de Virologie Structurale, Paris, France.
  • Rogers K; New Iberia Research Center and Department of Biology, University of Louisiana at Lafayette, New Iberia, LA 70560, USA.
  • O'Connor MA; Washington National Primate Research Center, Seattle, WA 98121, USA; Department of Microbiology, University of Washington, Seattle, WA 98195, USA.
  • Shirreff L; New Iberia Research Center and Department of Biology, University of Louisiana at Lafayette, New Iberia, LA 70560, USA.
  • Ferrell DE; New Iberia Research Center and Department of Biology, University of Louisiana at Lafayette, New Iberia, LA 70560, USA.
  • Bowen J; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • Brunette N; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
  • Kepl E; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
  • Zepeda SK; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • Starr T; Basic Sciences and Computational Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
  • Hsieh CL; Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.
  • Fiala B; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
  • Wrenn S; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
  • Pettie D; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
  • Sydeman C; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
  • Sprouse KR; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • Johnson M; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
  • Blackstone A; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
  • Ravichandran R; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
  • Ogohara C; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
  • Carter L; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
  • Tilles SW; Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington School of Medicine, Seattle, WA 98195, USA.
  • Rappuoli R; GSK, Siena, Italy.
  • Leist SR; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
  • Martinez DR; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
  • Clark M; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
  • Tisch R; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
  • O'Hagan DT; GSK, Rockville, MD, USA.
  • Van Der Most R; GSK, Rixensart, Belgium.
  • Van Voorhis WC; Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington School of Medicine, Seattle, WA 98195, USA.
  • Corti D; Humabs Biomed SA, a subsidiary of Vir Biotechnology, 6500 Bellinzona, Switzerland.
  • McLellan JS; Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.
  • Kleanthous H; Bill & Melinda Gates Foundation, Seattle, WA 98109, USA.
  • Sheahan TP; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
  • Smith KD; UW Medicine Department of Laboratory Medicine and Pathology, Seattle, WA 98195, USA.
  • Fuller DH; Washington National Primate Research Center, Seattle, WA 98121, USA; Department of Microbiology, University of Washington, Seattle, WA 98195, USA.
  • Villinger F; New Iberia Research Center and Department of Biology, University of Louisiana at Lafayette, New Iberia, LA 70560, USA.
  • Bloom J; Basic Sciences and Computational Biology, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA; Department of Genome Sciences, University of Washington, Seattle, WA 98109, USA.
  • Pulendran B; Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.
  • Baric RS; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
  • King NP; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA. Electronic address: neil@ipd.uw.edu.
  • Veesler D; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA. Electronic address: dveesler@uw.edu.
Cell ; 184(21): 5432-5447.e16, 2021 10 14.
Article in English | MEDLINE | ID: covidwho-1454060
ABSTRACT
Understanding vaccine-elicited protection against SARS-CoV-2 variants and other sarbecoviruses is key for guiding public health policies. We show that a clinical stage multivalent SARS-CoV-2 spike receptor-binding domain nanoparticle (RBD-NP) vaccine protects mice from SARS-CoV-2 challenge after a single immunization, indicating a potential dose-sparing strategy. We benchmarked serum neutralizing activity elicited by RBD-NPs in non-human primates against a lead prefusion-stabilized SARS-CoV-2 spike (HexaPro) using a panel of circulating mutants. Polyclonal antibodies elicited by both vaccines are similarly resilient to many RBD residue substitutions tested, although mutations at and surrounding position 484 have negative consequences for neutralization. Mosaic and cocktail nanoparticle immunogens displaying multiple sarbecovirus RBDs elicit broad neutralizing activity in mice and protect mice against SARS-CoV challenge even in the absence of SARS-CoV RBD in the vaccine. This study provides proof of principle that multivalent sarbecovirus RBD-NPs induce heterotypic protection and motivates advancing such broadly protective sarbecovirus vaccines to the clinic.
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Full text: Available Collection: International databases Database: MEDLINE Topics: Vaccines / Variants Language: English Journal: Cell Year: 2021 Document Type: Article Affiliation country: J.cell.2021.09.015

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Full text: Available Collection: International databases Database: MEDLINE Topics: Vaccines / Variants Language: English Journal: Cell Year: 2021 Document Type: Article Affiliation country: J.cell.2021.09.015