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Elicitation of Potent Neutralizing Antibody Responses by Designed Protein Nanoparticle Vaccines for SARS-CoV-2.
Walls, Alexandra C; Fiala, Brooke; Schäfer, Alexandra; Wrenn, Samuel; Pham, Minh N; Murphy, Michael; Tse, Longping V; Shehata, Laila; O'Connor, Megan A; Chen, Chengbo; Navarro, Mary Jane; Miranda, Marcos C; Pettie, Deleah; Ravichandran, Rashmi; Kraft, John C; Ogohara, Cassandra; Palser, Anne; Chalk, Sara; Lee, E-Chiang; Guerriero, Kathryn; Kepl, Elizabeth; Chow, Cameron M; Sydeman, Claire; Hodge, Edgar A; Brown, Brieann; Fuller, Jim T; Dinnon, Kenneth H; Gralinski, Lisa E; Leist, Sarah R; Gully, Kendra L; Lewis, Thomas B; Guttman, Miklos; Chu, Helen Y; Lee, Kelly K; Fuller, Deborah H; Baric, Ralph S; Kellam, Paul; Carter, Lauren; Pepper, Marion; Sheahan, Timothy P; Veesler, David; King, Neil P.
Afiliación
  • Walls AC; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • Fiala B; 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.
  • Wrenn S; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
  • Pham MN; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
  • Murphy M; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
  • Tse LV; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
  • Shehata L; Department of Immunology, University of Washington, Seattle, WA 98109, USA.
  • O'Connor MA; Department of Microbiology, University of Washington, Seattle, WA 98109, USA; Washington National Primate Research Center, Seattle, WA 98121, USA.
  • Chen C; Department of Medicinal Chemistry, University of Washington, Seattle, WA 98195, USA; Biological Physics Structure and Design Program, University of Washington, Seattle, WA 91895, USA.
  • Navarro MJ; 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.
  • Pettie D; 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.
  • Kraft JC; 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.
  • Palser A; Kymab Ltd., Babraham Research Campus, Cambridge, UK.
  • Chalk S; Kymab Ltd., Babraham Research Campus, Cambridge, UK.
  • Lee EC; Kymab Ltd., Babraham Research Campus, Cambridge, UK.
  • Guerriero K; Department of Microbiology, University of Washington, Seattle, WA 98109, USA; Washington National Primate Research Center, Seattle, WA 98121, USA.
  • Kepl E; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
  • Chow CM; 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.
  • Hodge EA; Department of Medicinal Chemistry, University of Washington, Seattle, WA 98195, USA.
  • Brown B; Department of Microbiology, University of Washington, Seattle, WA 98109, USA; Washington National Primate Research Center, Seattle, WA 98121, USA.
  • Fuller JT; Department of Microbiology, University of Washington, Seattle, WA 98109, USA.
  • Dinnon KH; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
  • Gralinski LE; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
  • Leist SR; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
  • Gully KL; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
  • Lewis TB; Department of Microbiology, University of Washington, Seattle, WA 98109, USA; Washington National Primate Research Center, Seattle, WA 98121, USA.
  • Guttman M; Department of Medicinal Chemistry, University of Washington, Seattle, WA 98195, USA.
  • Chu HY; Department of Medicine, University of Washington, Seattle, WA 98109, USA.
  • Lee KK; Department of Medicinal Chemistry, University of Washington, Seattle, WA 98195, USA; Biological Physics Structure and Design Program, University of Washington, Seattle, WA 91895, USA.
  • Fuller DH; Department of Microbiology, University of Washington, Seattle, WA 98109, USA; Washington National Primate Research Center, Seattle, WA 98121, USA; Center for Innate Immunity and Immune Disease, University of Washington, Seattle, WA 98109, USA.
  • Baric RS; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
  • Kellam P; Kymab Ltd., Babraham Research Campus, Cambridge, UK; Department of Infectious Disease, Imperial College, London, UK.
  • Carter L; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
  • Pepper M; Department of Immunology, University of Washington, Seattle, WA 98109, USA.
  • Sheahan TP; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
  • Veesler D; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA. Electronic address: dveesler@uw.edu.
  • 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.
Cell ; 183(5): 1367-1382.e17, 2020 11 25.
Article en En | MEDLINE | ID: mdl-33160446
ABSTRACT
A safe, effective, and scalable vaccine is needed to halt the ongoing SARS-CoV-2 pandemic. We describe the structure-based design of self-assembling protein nanoparticle immunogens that elicit potent and protective antibody responses against SARS-CoV-2 in mice. The nanoparticle vaccines display 60 SARS-CoV-2 spike receptor-binding domains (RBDs) in a highly immunogenic array and induce neutralizing antibody titers 10-fold higher than the prefusion-stabilized spike despite a 5-fold lower dose. Antibodies elicited by the RBD nanoparticles target multiple distinct epitopes, suggesting they may not be easily susceptible to escape mutations, and exhibit a lower bindingneutralizing ratio than convalescent human sera, which may minimize the risk of vaccine-associated enhanced respiratory disease. The high yield and stability of the assembled nanoparticles suggest that manufacture of the nanoparticle vaccines will be highly scalable. These results highlight the utility of robust antigen display platforms and have launched cGMP manufacturing efforts to advance the SARS-CoV-2-RBD nanoparticle vaccine into the clinic.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Vacunación / Nanopartículas / Anticuerpos Neutralizantes / Glicoproteína de la Espiga del Coronavirus / Dominios Proteicos / Vacunas contra la COVID-19 / SARS-CoV-2 / COVID-19 / Anticuerpos Antivirales Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Risk_factors_studies Límite: Adolescent / Adult / Aged / Animals / Female / Humans / Male / Middle aged Idioma: En Revista: Cell Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Vacunación / Nanopartículas / Anticuerpos Neutralizantes / Glicoproteína de la Espiga del Coronavirus / Dominios Proteicos / Vacunas contra la COVID-19 / SARS-CoV-2 / COVID-19 / Anticuerpos Antivirales Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Risk_factors_studies Límite: Adolescent / Adult / Aged / Animals / Female / Humans / Male / Middle aged Idioma: En Revista: Cell Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos