PT  - JOURNAL ARTICLE
AU  - Rémi Veneziano
AU  - Tyson J. Moyer
AU  - Matthew B. Stone
AU  - Tyson R. Shepherd
AU  - William R. Schief
AU  - Darrell J. Irvine
AU  - Mark Bathe
TI  - Role of nanoscale antigen organization on B-cell activation probed using DNA origami
AID  - 10.1101/2020.02.16.951475
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.02.16.951475
4099  - http://biorxiv.org/content/early/2020/02/17/2020.02.16.951475.short
4100  - http://biorxiv.org/content/early/2020/02/17/2020.02.16.951475.full
AB  - 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.