![]() ![]() Connected lines indicate adjacent positions located within 50–100 Å. ( e) Ferritin snub cube net with positions numbered similarly to panel d. Positions 2–6 are localized within a 100 Å distance from position 1. Twenty-four spatially dispersed antigens (colored individually) are displayed on the surface. ( d) Schematic model of ferritin-based np. Similar results were obtained from two independent experiments. The mAbs 3u-u (anti-NC99), 2D1 (anti-CA09) and C179 (anti-HA stem) were used to pull-down NC99, CA09 RBDs, and HA stem (control), respectively. ( c) Antigenic characterization of RBD-np by immunoprecipitation (IP). Shown are representative images from one experiment. RBD-np were made using either single building blocks ( left and middle) or two different building blocks ( right). ( b) Negative-stain EM images of self-assembled HA RBD-nps. SP, signal peptide T/C, transmembrane/cytoplasmic domains. Alteration in the residue 98 (Y98F) was made to abrogate sialic acid-binding property of HA. The mosaic antigen array signifies a unique approach that subverts monotypic immunodominance and allows otherwise subdominant cross-reactive B cell responses to emerge. Furthermore, we identified a broadly neutralizing monoclonal antibody in a mouse immunized with mosaic RBD-np. 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. 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. 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. This necessitates new approaches that provide broader protection against influenza. present vaccine against influenza virus has the inevitable risk of antigenic discordance between the vaccine and the circulating strains, which diminishes vaccine efficacy.
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