Your browser doesn't support javascript.
loading
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; 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.
Afiliação
  • Walls AC; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • Fiala B; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • Schäfer A; institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
  • Wrenn S; 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.
  • Murphy M; institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
  • Tse LV; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • Shehata L; institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
  • O'Connor MA; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • Chen C; institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
  • Navarro MJ; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
  • Miranda MC; Department of Immunology, University of Washington, Seattle, WA 98109, USA.
  • Pettie D; Department of Microbiology, University of Washington, Seattle, WA 98109, USA.
  • Ravichandran R; Washington National Primate Research Center, Seattle, WA 98121, USA.
  • Kraft JC; Department of Medicinal Chemistry, University of Washington, Seattle, WA 98195, USA.
  • Ogohara C; Biological Physics Structure and Design Program, University of Washington, Seattle, WA 91895, USA.
  • Palser A; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • Chalk S; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • Lee EC; institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
  • Kepl E; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • Chow CM; institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
  • Sydeman C; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • Hodge EA; institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
  • Brown B; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • Fuller JT; institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
  • Dinnon KH; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • Gralinski LE; institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
  • Leist SR; Kymab Ltd, Babraham Research Campus, Cambridge, United Kingdom.
  • Gully KL; Kymab Ltd, Babraham Research Campus, Cambridge, United Kingdom.
  • Lewis TB; Kymab Ltd, Babraham Research Campus, Cambridge, United Kingdom.
  • Guttman M; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • Chu HY; institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
  • Lee KK; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • Fuller DH; institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
  • Baric RS; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.
  • Kellam P; institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
  • Carter L; Department of Medicinal Chemistry, University of Washington, Seattle, WA 98195, USA.
  • Pepper M; Department of Microbiology, University of Washington, Seattle, WA 98109, USA.
  • Sheahan TP; Washington National Primate Research Center, Seattle, WA 98121, USA.
  • Veesler D; Department of Microbiology, University of Washington, Seattle, WA 98109, USA.
  • King NP; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27514, USA.
bioRxiv ; 2020 Aug 12.
Article em En | MEDLINE | ID: mdl-32817941
A safe, effective, and scalable vaccine is urgently needed to halt the ongoing SARS-CoV-2 pandemic. Here, 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 copies of the SARS-CoV-2 spike (S) glycoprotein receptor-binding domain (RBD) in a highly immunogenic array and induce neutralizing antibody titers roughly ten-fold higher than the prefusion-stabilized S ectodomain trimer despite a more than five-fold lower dose. Antibodies elicited by the nanoparticle immunogens target multiple distinct epitopes on the RBD, suggesting that they may not be easily susceptible to escape mutations, and exhibit a significantly lower binding:neutralizing ratio than convalescent human sera, which may minimize the risk of vaccine-associated enhanced respiratory disease. The high yield and stability of the protein components and assembled nanoparticles, especially compared to the SARS-CoV-2 prefusion-stabilized S trimer, suggest that manufacture of the nanoparticle vaccines will be highly scalable. These results highlight the utility of robust antigen display platforms for inducing potent neutralizing antibody responses and have launched cGMP manufacturing efforts to advance the lead RBD nanoparticle vaccine into the clinic.

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: BioRxiv Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: BioRxiv Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Estados Unidos