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Mosaic nanoparticle display of diverse influenza virus hemagglutinins elicits broad B cell responses

  1. Author:
    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.

  2. Author Address

    NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.NIAID, Lab Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Canc Res Technol Program, Electron Microscope Lab, Frederick, MD USA.Bioqual Inc, Rockville, MD USA.Walter Reed Army Inst Res, Henry M Jackson Fdn Adv Mil Med, US Mil HIV Res Program, Silver Spring, MD USA.Qatar Univ, Biomed Res Ctr, Doha, Qatar.Univ Melbourne, Peter Doherty Inst Infect & Immun, Dept Microbiol & Immunol, Melbourne, Vic, Australia.Vanderbilt Univ, Med Ctr, Vanderbilt Vaccine Ctr, Nashville, TN USA.Vanderbilt Univ, Med Ctr, Dept Pathol, Nashville, TN 37232 USA.Frederick Natl Lab Canc Res, Canc Res Technol Program, Cryo EM Facil, Frederick, MD USA.
    1. Year: 2019
    2. Date: Mar
    3. Epub Date: 2019 02 11
  2. Journal: Nature immunology
  3. NATURE PUBLISHING GROUP,
    1. 20
    2. 3
    3. Pages: 362-372
  5. Type of Article: Article
  6. ISSN: 1529-2908
  1. 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.

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External Sources

  1. View Full Text
  2. DOI: 10.1038/s41590-018-0305-x
  3. PMID: 30742080
  4. PMCID: PMC6380945
  5. View record in Web of Science®
  6. WOS: 000458893600020

Library Notes

  1. Fiscal Year: FY2018-2019
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