Design of nanoparticulate group 2 influenza hemagglutinin stem antigens that activate unmutated ancestor B cell receptors of broadly neutralizing antibody lineages
Kizzmekia S. Corbett,
Syed M Moin,
HADI M. YASSINE,
Sky I Myers,
Adam K Wheatley,
Chaim A Schramm,
Rebecca A Gillespie,
Sarah F Andrews,
M. Gordon Joyce,
Michelle C Crank,
Daniel C Douek,
Adrian B. McDermott,
John R Mascola,
Barney S Graham,
Jeffrey C Boyington
Posted 17 Dec 2018
bioRxiv DOI: 10.1101/497123 (published DOI: 10.1128/mBio.02810-18)
Posted 17 Dec 2018
Influenza vaccines targeting the highly-conserved stem of the hemagglutinin (HA) surface glycoprotein have the potential to protect against pandemic and drifted seasonal influenza viruses not covered by current vaccines. While HA stem-based immunogens derived from group 1 influenza A have been shown to induce intra-group heterosubtypic protection, HA stem-specific antibody lineages originating from group 2 may be more likely to possess broad cross-group reactivity. We report the structure-guided development of mammalian cell-expressed candidate vaccine immunogens based on influenza A group 2 H3 and H7 HA stem trimers displayed on self-assembling ferritin nanoparticles using an iterative, multipronged approach involving helix stabilization, loop optimization, disulfide bond addition, and side chain repacking. These immunogens were thermostable, formed uniform and symmetric nanoparticles, were recognized by cross-group-reactive broadly neutralizing antibodies (bNAbs) with nanomolar affinity, and elicited protective, homosubtypic antibodies in mice. Importantly, several immunogens were able to activate B cells expressing inferred unmutated common ancestor (UCA) versions of cross-group-reactive human bNAbs from two multi-donor classes, suggesting they could initiate elicitation of these bNAbs in humans.
- Downloaded 431 times
- Download rankings, all-time:
- Site-wide: 78,862
- In immunology: 2,373
- Year to date:
- Site-wide: 115,694
- Since beginning of last month:
- Site-wide: 108,783
Downloads over time
Distribution of downloads per paper, site-wide
- 27 Nov 2020: The website and API now include results pulled from medRxiv as well as bioRxiv.
- 18 Dec 2019: We're pleased to announce PanLingua, a new tool that enables you to search for machine-translated bioRxiv preprints using more than 100 different languages.
- 21 May 2019: PLOS Biology has published a community page about Rxivist.org and its design.
- 10 May 2019: The paper analyzing the Rxivist dataset has been published at eLife.
- 1 Mar 2019: We now have summary statistics about bioRxiv downloads and submissions.
- 8 Feb 2019: Data from Altmetric is now available on the Rxivist details page for every preprint. Look for the "donut" under the download metrics.
- 30 Jan 2019: preLights has featured the Rxivist preprint and written about our findings.
- 22 Jan 2019: Nature just published an article about Rxivist and our data.
- 13 Jan 2019: The Rxivist preprint is live!