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


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2019-03

AUTHORS

Masaru Kanekiyo, M. Gordon Joyce, Rebecca A. Gillespie, John R. Gallagher, Sarah F. Andrews, Hadi M. Yassine, Adam K. Wheatley, Brian E. Fisher, David R. Ambrozak, Adrian Creanga, Kwanyee Leung, Eun Sung Yang, Seyhan Boyoglu-Barnum, Ivelin S. Georgiev, Yaroslav Tsybovsky, Madhu S. Prabhakaran, Hanne Andersen, Wing-Pui Kong, Ulrich Baxa, Kathryn L. Zephir, Julie E. Ledgerwood, Richard A. Koup, Peter D. Kwong, Audray K. Harris, Adrian B. McDermott, John R. Mascola, Barney S. Graham

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. More... »

PAGES

362-372

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41590-018-0305-x

DOI

http://dx.doi.org/10.1038/s41590-018-0305-x

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1112056518

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30742080


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464 https://www.grid.ac/institutes/grid.418021.e schema:alternateName Frederick National Laboratory for Cancer Research
465 schema:name Cryo-EM facility, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Frederick, MD, USA
466 Electron Microscope Laboratory, Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer Research, Frederick, MD, USA
467 rdf:type schema:Organization
468 https://www.grid.ac/institutes/grid.419681.3 schema:alternateName National Institute of Allergy and Infectious Diseases
469 schema:name 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
470 Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
471 Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
472 rdf:type schema:Organization
 




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