Role of nanoscale antigen organization on B-cell activation probed using DNA origami
Name
2020.02.16.951475v1.full.pdf
Description
Submitted version
Size
6.69 MB
Format
Adobe PDF
Checksum (MD5)
41dcf3d7f348aaace2f521e7c786219a
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
Date Issued
2020
Journal
Nature Nanotechnology
Publisher
Springer Science and Business Media LLC
Version
Original manuscript
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.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Koch Institute for Integrative Cancer Research at MIT
Massachusetts Institute of Technology. Department of Materials Science and Engineering
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1038/s41565-020-0719-0
