Elicitation of broadly protective sarbecovirus immunity by receptor-binding domain nanoparticle vaccines

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  • Walls, Alexandra
    • Other Affiliation: University of Washington
  • Miranda, Marcos C.
    • Other Affiliation: University of Washington
  • Schäfer, Alexandra
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Pham, Minh N.
    • Other Affiliation: University of Washington
  • Greaney, Allison
    • Other Affiliation: Fred Hutchinson Cancer Research Center
  • Arunachalam, Prabhu S.
    • Other Affiliation: Stanford University
  • Navarro, Mary-Jane
    • Other Affiliation: University of Washington
  • Tortorici, M. Alejandra
    • Other Affiliation: University of Washington
  • Rogers, Kenneth
    • Other Affiliation: University of Louisiana at Lafayette
  • O'Connor, Megan
    • Other Affiliation: University of Washington
  • Shirreff, Lisa
    • Other Affiliation: University of Louisiana at Lafayette
  • Ferrell, Douglas E.
    • Other Affiliation: University of Louisiana at Lafayette
  • Bowen, John
    • Other Affiliation: University of Washington
  • Brunette, Natalie
    • Other Affiliation: University of Washington
  • Kepl, Elizabeth
    • Other Affiliation: University of Washington
  • Zepeda, Samantha K.
    • Other Affiliation: University of Washington
  • Starr, Tyler
    • Other Affiliation: Fred Hutchinson Cancer Research Center
  • Hsieh, Ching-Lin
    • Other Affiliation: The University of Texas at Austin
  • Fiala, Brooke
    • Other Affiliation: University of Washington
  • Wrenn, Samuel
    • Other Affiliation: University of Washington
  • Pettie, Deleah
    • Other Affiliation: University of Washington
  • Sydeman, Claire
    • Other Affiliation: University of Washington
  • Sprouse, Kaitlin R.
    • Other Affiliation: University of Washington
  • Johnson, Max
    • Other Affiliation: University of Washington
  • Blackstone, Alyssa
    • Other Affiliation: University of Washington
  • Ravichandran, Rashimi
    • Other Affiliation: University of Washington
  • Ogohara, Cassandra
    • Other Affiliation: University of Washington
  • Carter, Lauren
    • Other Affiliation: University of Washington
  • Tilles, Sasha W.
    • Other Affiliation: University of Washington School of Medicine
  • Rappuoli, Rino
    • Other Affiliation: GSK
  • Leist, Sarah R.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Martinez, David R.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Clark, Matthew
    • Affiliation: School of Medicine, Department of Microbiology and Immunology
  • Tisch, Roland
    • Affiliation: N.C. Cancer Hospital, UNC Lineberger Comprehensive Cancer Center
  • O'Hagan, Derek T.
    • Other Affiliation: GSK
  • Van Der Most, Robbert
    • Other Affiliation: GSK
  • Van Voorhis, Wesley C.
    • Other Affiliation: University of Washington School of Medicine
  • Corti, Davide
    • Other Affiliation: Humabs Biomed SA
  • McLellan, Jason S.
    • Other Affiliation: The University of Texas at Austin
  • Kleanthous, Harry
    • Other Affiliation: Bill and Melinda Gates Foundation
  • Sheahan, Timothy P.
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Smith, Kelly D.
    • Other Affiliation: UW Medicine Department of Laboratory Medicine and Pathology
  • Fuller, Deborah J.
    • Other Affiliation: University of Washington
  • Villinger, Francois
    • Other Affiliation: University of Louisiana at Lafayette
  • Bloom, Jesse
    • Other Affiliation: University of Washington
  • Pulendran, Bali
    • Other Affiliation: Stanford University
  • Baric, Ralph
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • King, Neal P.
    • Other Affiliation: University of Washington
  • Veesler, David
    • Other Affiliation: University of Washington
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 vaccine (RBD-NP) 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-NP 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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  • Article
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  • In Copyright
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  • Attribution-NonCommercial-NoDerivs 3.0 United States
Journal title
  • Cell
Language
  • English
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  • Postprint

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