期刊
NATURE NANOTECHNOLOGY
卷 15, 期 8, 页码 716-+出版社
NATURE RESEARCH
DOI: 10.1038/s41565-020-0719-0
关键词
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资金
- Human Frontier Science Program [RGP0029/2014]
- Office of Naval Research [N00014-16-1-2953]
- US Army Research Office through the Institute for Soldier Nanotechnologies at MIT [W911NF-18-2-0048]
- Ragon Institute of MGH
- Ragon Institute of MIT
- Ragon Institute of Harvard
- NIH [R21-EB026008, R01-MH112694, AI048240, UM1AI144462, UM1AI100663, R01-AI 143740, R01-AI 146581]
- IAVI Neutralizing Antibody Consortium (NAC) and Center
- Collaboration for AIDS Vaccine Discovery
- Feodor Lynen Fellowship of the Alexander von Humboldt Foundation
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 similar 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.
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