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

Nat Immunol. 2019; 
Kanekiyo 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.
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Codon Optimization All genes used in the study were human codon optimized (GenScript).... Heavy- and light-chain sequences were synthesized and cloned by Genscript into murine IgG2a and kappa expression vectors. Get A Quote

摘要

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... More

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