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bioRxiv · 10.1101/2020.02.16.951475

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

Veneziano, R.·Moyer, T.·Stone, M. B.·Shepherd, T. R.·Schief, W. R.·Irvine, D. J.·Bathe, M.
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Abstract

Arraying vaccine immunogens in a multivalent form on the surface of virus-like particles is an important strategy used to enhance the efficacy of subunit vaccines. However, the impacts of antigen valency, spacing, and spatial organization on B cell triggering remain poorly understood. Here, we use DNA origami nanoparticles to create precise nanoscale organizations of a clinically-relevant HIV gp120 immunogen to systematically interrogate their impact on B cell triggering in vitro. We find that antigen dimers elicit monotonically increasing B cell receptor activation as inter-antigen spacing increases up to ~30 nm, and only 5 immunogens arrayed on the surface of a 3D particle are needed to elicit maximal B cell calcium signaling. Our results reveal design principles of viral and immunogen display that drive functional B cell responses.

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Veneziano, R., Moyer, T., Stone, M. B., Shepherd, T. R., Schief, W. R., Irvine, D. J., Bathe, M.. 2020-02-17. Role of nanoscale antigen organization on B-cell activation probed using DNA origami. https://doi.org/10.1101/2020.02.16.951475

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