Your browser doesn't support javascript.
loading
Mosaic nanoparticle display of diverse influenza virus hemagglutinins elicits broad B cell responses.
Kanekiyo, Masaru; Joyce, M Gordon; Gillespie, Rebecca A; Gallagher, John R; Andrews, Sarah F; Yassine, Hadi M; Wheatley, Adam K; Fisher, Brian E; Ambrozak, David R; Creanga, Adrian; Leung, Kwanyee; Yang, Eun Sung; Boyoglu-Barnum, Seyhan; Georgiev, Ivelin S; Tsybovsky, Yaroslav; Prabhakaran, Madhu S; Andersen, Hanne; Kong, Wing-Pui; Baxa, Ulrich; Zephir, Kathryn L; Ledgerwood, Julie E; Koup, Richard A; Kwong, Peter D; Harris, Audray K; McDermott, Adrian B; Mascola, John R; Graham, Barney S.
Afiliação
  • Kanekiyo M; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. kanekiyom@nih.gov.
  • Joyce MG; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Gillespie RA; Henry M. Jackson Foundation for the Advancement of Military Medicine, US Military HIV Research Program, Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Gallagher JR; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Andrews SF; Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Yassine HM; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Wheatley AK; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Fisher BE; Biomedical Research Center, Qatar University, Doha, Qatar.
  • Ambrozak DR; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Creanga A; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia.
  • Leung K; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Yang ES; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Boyoglu-Barnum S; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Georgiev IS; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Tsybovsky Y; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Prabhakaran MS; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Andersen H; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Kong WP; Vanderbilt Vaccine Center and Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Baxa U; Electron Microscope Laboratory, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
  • Zephir KL; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Ledgerwood JE; Bioqual, Inc., Rockville, MD, USA.
  • Koup RA; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Kwong PD; Electron Microscope Laboratory, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
  • Harris AK; Cryo-EM facility, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
  • McDermott AB; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Mascola JR; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Graham BS; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Nat Immunol ; 20(3): 362-372, 2019 03.
Article em En | MEDLINE | ID: mdl-30742080
ABSTRACT
The present vaccine against influenza virus has the inevitable risk of antigenic discordance between the vaccine and the circulating strains, which diminishes vaccine efficacy. This necessitates new approaches that provide broader protection against influenza. Here we designed a vaccine using the hypervariable receptor-binding domain (RBD) of viral hemagglutinin displayed on a nanoparticle (np) able to elicit antibody responses that neutralize H1N1 influenza viruses spanning over 90 years. Co-display of RBDs from multiple strains across time, so that the adjacent RBDs are heterotypic, provides an avidity advantage to cross-reactive B cells. Immunization with the mosaic RBD-np elicited broader antibody responses than those induced by an admixture of nanoparticles encompassing the same set of RBDs as separate homotypic arrays. Furthermore, we identified a broadly neutralizing monoclonal antibody in a mouse immunized with mosaic RBD-np. The mosaic antigen array signifies a unique approach that subverts monotypic immunodominance and allows otherwise subdominant cross-reactive B cell responses to emerge.
Assuntos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Vacinas contra Influenza / Infecções por Orthomyxoviridae / Glicoproteínas de Hemaglutininação de Vírus da Influenza / Influenza Humana / Vírus da Influenza A Subtipo H1N1 / Nanopartículas Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Vacinas contra Influenza / Infecções por Orthomyxoviridae / Glicoproteínas de Hemaglutininação de Vírus da Influenza / Influenza Humana / Vírus da Influenza A Subtipo H1N1 / Nanopartículas Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article