Mosaic nanoparticle display of diverse influenza virus hemagglutinins elicits broad B cell responses
Masaru Kanekiyo, M Gordon Joyce, Rebecca A Gillespie, John R Gallagher, Sarah F Andrews, Hadi M Yassine, Adam K Wheatley, Brian E Fisher, David R Ambrozak, Adrian Creanga, Kwanyee Leung, Eun Sung Yang, Seyhan Boyoglu-Barnum, Ivelin S Georgiev, Yaroslav Tsybovsky, Madhu S Prabhakaran, Hanne Andersen, Wing-Pui Kong, Ulrich Baxa, Kathryn L Zephir Show all
Nature Immunology | NATURE PUBLISHING GROUP | Published : 2019
The present vaccine against influenza virus has the inevitable risk of antigenic discordance between the vaccine and the circulating strains, which diminishes vaccine efficacy. This necessitates new approaches that provide broader protection against influenza. Here we designed a vaccine using the hypervariable receptor-binding domain (RBD) of viral hemagglutinin displayed on a nanoparticle (np) able to elicit antibody responses that neutralize H1N1 influenza viruses spanning over 90 years. Co-display of RBDs from multiple strains across time, so that the adjacent RBDs are heterotypic, provides an avidity advantage to cross-reactive B cells. Immunization with the mosaic RBD-np elicited broade..View full abstract
Awarded by US Department of Energy, Office of Science, Basic Energy Sciences
Awarded by Frederick National Laboratory for Cancer Research, NIH
We thank J. Weir (Food and Drug Administration) for providing influenza viruses; R. Webby (St Jude Children's Research Hospital) for influenza reverse genetics plasmids; M. Dillon, K. Wuddie, G. Sarbador, C. Chiedi, A. Taylor, H. Bao and D. Scorpio (VRC) for help with animal studies; A. Kumar (VRC) for help with protein production; V. Nair and E. Fischer (NIAID) for cryo-electron microscopy data collection; M. Chen (VRC), D. Angeletti and J. Yewdell (NIAID) for help with initial epitope mapping. This work used the computational resources of the NIH HPC Biowulf cluster (http://hpc.nih.gov) and also the Office of Cyber Infrastructure and Computational Biology (OCICB) High Performance Computing (HPC) cluster at the NIAID, NIH. Use of insertion device 22 (SER-CAT) at the Advanced Photon Source was supported by the US Department of Energy, Office of Science, Basic Energy Sciences (under contract W-31-109-Eng-38). Support for this work was provided by the NIAID Intramural Research Program to the VRC and Division of Intramural Research. This work was also supported in part with federal funds from the Frederick National Laboratory for Cancer Research, NIH (under contract HHSN261200800001E).