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Combinatorial immune refocusing within the influenza hemagglutinin RBD improves cross-neutralizing antibody responses.
Dosey, Annie; Ellis, Daniel; Boyoglu-Barnum, Seyhan; Syeda, Hubza; Saunders, Mason; Watson, Michael J; Kraft, John C; Pham, Minh N; Guttman, Miklos; Lee, Kelly K; Kanekiyo, Masaru; King, Neil P.
Afiliación
  • Dosey A; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
  • Ellis D; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
  • Boyoglu-Barnum S; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Syeda H; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Saunders M; Department of Medicinal Chemistry, University of Washington, Seattle, WA 98195, USA.
  • Watson MJ; Department of Medicinal Chemistry, 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.
  • Pham MN; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA.
  • Guttman M; Department of Medicinal Chemistry, University of Washington, Seattle, WA 98195, USA.
  • Lee KK; Department of Medicinal Chemistry, University of Washington, Seattle, WA 98195, USA.
  • Kanekiyo M; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, 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: neilking@uw.edu.
Cell Rep ; 42(12): 113553, 2023 12 26.
Article en En | MEDLINE | ID: mdl-38096052
The receptor-binding domain (RBD) of influenza virus hemagglutinin (HA) elicits potently neutralizing yet mostly strain-specific antibodies. Here, we evaluate the ability of several immunofocusing techniques to enhance the functional breadth of vaccine-elicited immune responses against the HA RBD. We present a series of "trihead" nanoparticle immunogens that display native-like closed trimeric RBDs from the HAs of several H1N1 influenza viruses. The series includes hyperglycosylated and hypervariable variants that incorporate natural and designed sequence diversity at key positions in the receptor-binding site periphery. Nanoparticle immunogens displaying triheads or hyperglycosylated triheads elicit higher hemagglutination inhibition (HAI) and neutralizing activity than the corresponding immunogens lacking either trimer-stabilizing mutations or hyperglycosylation. By contrast, mosaic nanoparticle display and antigen hypervariation do not significantly alter the magnitude or breadth of vaccine-elicited antibodies. Our results yield important insights into antibody responses against the RBD and the ability of several structure-based immunofocusing techniques to influence vaccine-elicited antibody responses.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vacunas contra la Influenza / Infecciones por Orthomyxoviridae / Gripe Humana / Subtipo H1N1 del Virus de la Influenza A Límite: Humans Idioma: En Revista: Cell Rep Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vacunas contra la Influenza / Infecciones por Orthomyxoviridae / Gripe Humana / Subtipo H1N1 del Virus de la Influenza A Límite: Humans Idioma: En Revista: Cell Rep Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos