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Role of nanoscale antigen organization on B-cell activation probed using DNA origami

Author(s)
Veneziano, Rémi; Moyer, Tyson J; Stone, Matthew B; Wamhoff, Eike-Christian; Read, Benjamin J; Mukherjee, Sayak; Shepherd, Tyson R; Das, Jayajit; Schief, William R; Irvine, Darrell J; Bathe, Mark; ... Show more Show less
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Abstract
© 2020, The Author(s), under exclusive licence to Springer Nature Limited. Vaccine efficacy can be increased by arraying immunogens in multivalent form on virus-like nanoparticles to enhance B-cell activation. However, the effects of antigen copy number, spacing and affinity, as well as the dimensionality and rigidity of scaffold presentation on B-cell activation remain poorly understood. Here, we display the clinical vaccine immunogen eOD-GT8, an engineered outer domain of the HIV-1 glycoprotein-120, on DNA origami nanoparticles to systematically interrogate the impact of these nanoscale parameters on B-cell activation in vitro. We find that B-cell signalling is maximized by as few as five antigens maximally spaced on the surface of a 40-nm viral-like nanoparticle. Increasing antigen spacing up to ~25–30 nm monotonically increases B-cell receptor activation. Moreover, scaffold rigidity is essential for robust B-cell triggering. These results reveal molecular vaccine design principles that may be used to drive functional B-cell responses.
Date issued
2020
URI
https://hdl.handle.net/1721.1/134091
Journal
Nature Nanotechnology
Publisher
Springer Science and Business Media LLC

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