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Computationally designed mRNA-launched protein nanoparticle vaccines.
Hendricks, Grace G; Grigoryan, Lilit; Navarro, Mary Jane; Catanzaro, Nicholas J; Hubbard, Miranda L; Powers, John M; Mattocks, Melissa; Treichel, Catherine; Walls, Alexandra C; Lee, Jimin; Ellis, Daniel; Wang, Jing Yang John; Cheng, Suna; Miranda, Marcos C; Valdez, Adian; Chao, Cara W; Chan, Sidney; Men, Christine; Johnson, Max R; Hui, Harold; Wu, Sheng-Yang; Lujan, Victor; Muramatsu, Hiromi; Lin, Paulo J C; Sung, Molly M H; Tam, Ying K; Leaf, Elizabeth M; Pardi, Norbert; Baric, Ralph S; Pulendran, Bali; Veesler, David; Schäfer, Alexandra; King, Neil P.
Afiliación
  • Hendricks GG; Institute for Protein Design, University of Washington, Seattle, WA, USA.
  • Grigoryan L; Department of Biochemistry, University of Washington, Seattle, WA, USA.
  • Navarro MJ; Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.
  • Catanzaro NJ; Department of Biochemistry, University of Washington, Seattle, WA, USA.
  • Hubbard ML; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Powers JM; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Mattocks M; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Treichel C; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Walls AC; Institute for Protein Design, University of Washington, Seattle, WA, USA.
  • Lee J; Department of Biochemistry, University of Washington, Seattle, WA, USA.
  • Ellis D; Department of Biochemistry, University of Washington, Seattle, WA, USA.
  • Wang JYJ; Howard Hughes Medical Institute, Seattle, WA, USA.
  • Cheng S; Department of Biochemistry, University of Washington, Seattle, WA, USA.
  • Miranda MC; Institute for Protein Design, University of Washington, Seattle, WA, USA.
  • Valdez A; Department of Biochemistry, University of Washington, Seattle, WA, USA.
  • Chao CW; Institute for Protein Design, University of Washington, Seattle, WA, USA.
  • Chan S; Department of Biochemistry, University of Washington, Seattle, WA, USA.
  • Men C; Institute for Protein Design, University of Washington, Seattle, WA, USA.
  • Johnson MR; Department of Biochemistry, University of Washington, Seattle, WA, USA.
  • Hui H; Institute for Protein Design, University of Washington, Seattle, WA, USA.
  • Wu SY; Department of Biochemistry, University of Washington, Seattle, WA, USA.
  • Lujan V; Institute for Protein Design, University of Washington, Seattle, WA, USA.
  • Muramatsu H; Department of Biochemistry, University of Washington, Seattle, WA, USA.
  • Lin PJC; Institute for Protein Design, University of Washington, Seattle, WA, USA.
  • Sung MMH; Department of Biochemistry, University of Washington, Seattle, WA, USA.
  • Tam YK; Graduate Program in Molecular and Cellular Biology, University of Washington, Seattle, WA, USA.
  • Leaf EM; Institute for Protein Design, University of Washington, Seattle, WA, USA.
  • Pardi N; Department of Biochemistry, University of Washington, Seattle, WA, USA.
  • Baric RS; Institute for Protein Design, University of Washington, Seattle, WA, USA.
  • Pulendran B; Department of Biochemistry, University of Washington, Seattle, WA, USA.
  • Veesler D; Institute for Protein Design, University of Washington, Seattle, WA, USA.
  • Schäfer A; Department of Biochemistry, University of Washington, Seattle, WA, USA.
  • King NP; Institute for Immunity, Transplantation and Infection, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.
bioRxiv ; 2024 Jul 23.
Article en En | MEDLINE | ID: mdl-39091730
ABSTRACT
Both protein nanoparticle and mRNA vaccines were clinically de-risked during the COVID-19 pandemic1-6. These vaccine modalities have complementary strengths antigen display on protein nanoparticles can enhance the magnitude, quality, and durability of antibody responses7-10, while mRNA vaccines can be rapidly manufactured11 and elicit antigen-specific CD4 and CD8 T cells12,13. Here we leverage a computationally designed icosahedral protein nanoparticle that was redesigned for optimal secretion from eukaryotic cells14 to develop an mRNA-launched nanoparticle vaccine for SARS-CoV-2. The nanoparticle, which displays 60 copies of a stabilized variant of the Wuhan-Hu-1 Spike receptor binding domain (RBD)15, formed monodisperse, antigenically intact assemblies upon secretion from transfected cells. An mRNA vaccine encoding the secreted RBD nanoparticle elicited 5- to 28-fold higher levels of neutralizing antibodies than an mRNA vaccine encoding membrane-anchored Spike, induced higher levels of CD8 T cells than the same immunogen when delivered as an adjuvanted protein nanoparticle, and protected mice from vaccine-matched and -mismatched SARS-CoV-2 challenge. Our data establish that delivering protein nanoparticle immunogens via mRNA vaccines can combine the benefits of each modality and, more broadly, highlight the utility of computational protein design in genetic immunization strategies.
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Texto completo: 1 Banco de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
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XML
PubMed Links
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Texto completo: 1 Banco de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos