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AuthorKanekiyo, Masaru
AuthorJoyce, M Gordon
AuthorGillespie, Rebecca A
AuthorGallagher, John R
AuthorAndrews, Sarah F
AuthorYassine, Hadi M
AuthorWheatley, Adam K
AuthorFisher, Brian E
AuthorAmbrozak, David R
AuthorCreanga, Adrian
AuthorLeung, Kwanyee
AuthorYang, Eun Sung
AuthorBoyoglu-Barnum, Seyhan
AuthorGeorgiev, Ivelin S
AuthorTsybovsky, Yaroslav
AuthorPrabhakaran, Madhu S
AuthorAndersen, Hanne
AuthorKong, Wing-Pui
AuthorBaxa, Ulrich
AuthorZephir, Kathryn L
AuthorLedgerwood, Julie E
AuthorKoup, Richard A
AuthorKwong, Peter D
AuthorHarris, Audray K
AuthorMcDermott, Adrian B
AuthorMascola, John R
AuthorGraham, Barney S
Available date2019-03-05T11:19:21Z
Publication Date2019-03-01
Publication NameNature Immunology
Identifierhttp://dx.doi.org/10.1038/s41590-018-0305-x
CitationKanekiyo M, Joyce MG, Gillespie RA, Gallagher JR, Andrews SF, Yassine HM, Wheatley AK, Fisher BE, Ambrozak DR, Creanga A, Leung K, Yang ES, Boyoglu-Barnum S, Georgiev IS, Tsybovsky Y, Prabhakaran MS, Andersen H, Kong WP, Baxa U, Zephir KL, Ledgerwood JE, Koup RA, Kwong PD, Harris AK, McDermott AB, Mascola JR, Graham BS. Mosaic nanoparticle display of diverse influenza virus hemagglutinins elicits broad B cell responses. Nat Immunol. 2019 Mar;20(3):362-372. doi: 10.1038/s41590-018-0305-x.
ISSN1529-2908
URIhttp://hdl.handle.net/10576/11373
AbstractThe 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.
Languageen
PublisherNature Research
Subjectnanoparticle
influenza virus
TitleMosaic nanoparticle display of diverse influenza virus hemagglutinins elicits broad B cell responses.
TypeArticle
Pagination362-372
Issue Number3
Volume Number20
ESSN1529-2916
dc.accessType Abstract Only


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