Elicitation of broadly protective immunity to influenza by multivalent hemagglutinin nanoparticle vaccines
Rebecca A Gillespie,
Geoffrey B. Hutchinson,
Syed M Moin,
Michael J Watson,
John R Vaile,
Michelle C Crank,
Kelly K. Lee,
John R. Mascola,
Neil P. King,
Posted 31 May 2020
bioRxiv DOI: 10.1101/2020.05.30.125179
Posted 31 May 2020
Influenza vaccines that confer broad and durable protection against diverse virus strains would have a major impact on global health. However, next-generation vaccine design efforts have been complicated by challenges including the genetic plasticity of the virus and the immunodominance of certain epitopes in its glycoprotein antigens. Here we show that computationally designed, two-component nanoparticle immunogens induce potently neutralizing and broadly protective antibody responses against a wide variety of influenza viruses. The nanoparticle immunogens display 20 hemagglutinin (HA) trimers in a highly immunogenic array, and their assembly in vitro enables precisely controlled co-display of multiple distinct HAs in defined ratios. Nanoparticle immunogens displaying the four HAs of licensed quadrivalent influenza vaccines (QIV) elicited hemagglutination inhibition and neutralizing antibody responses to vaccine-matched strains that were equivalent or superior to commercial QIV in mice, ferrets, and nonhuman primates. The nanoparticle immunogens -but not QIV- simultaneously induced broadly protective antibody responses to heterologous viruses, including H5N1 and H7N9, by targeting the subdominant yet conserved HA stem. Unlike previously reported influenza vaccine candidates, our nanoparticle immunogens can alter the intrinsic immunodominance hierarchy of HA to induce both potent receptor-blocking and broadly cross-reactive stem-directed antibody responses and are attractive candidates for a next-generation influenza vaccine that could replace current seasonal vaccines. ### Competing Interest Statement S.B.B., D.E., R.A.G., B.S.G., N.P.K., and M.K. are listed as inventors on a patent application based on the studies presented in this paper.
- Downloaded 878 times
- Download rankings, all-time:
- Site-wide: 17,087 out of 105,862
- In immunology: 531 out of 3,257
- Year to date:
- Site-wide: 3,521 out of 105,862
- Since beginning of last month:
- Site-wide: 5,940 out of 105,862
Downloads over time
Distribution of downloads per paper, site-wide
- 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!