Double-layered protein nanoparticles induce broad protection against divergent influenza A viruses

• Type of Material: Article
• Authors: Lei Deng, Georgia State University; Teena Mohan, Georgia State University; Timothy Z. Chang, Georgia State University; Gilbert X. Gonzalez, Georgia State University; Ye Wang, Georgia State University; Young-Man Kwon, Georgia State University; Sang-Moo Kang, Georgia State University; Richard W Compans, Emory University; Julie A. Champion, Georgia State University; Bao-Zhong Wang, Georgia State University
• Language: English
• Date: 2018-01-24
• Publisher: Nature Publishing Group
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2018
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41467-017-02725-4
• Title of Journal or Parent Work: Nature Communications
• ISSN: 2041-1723
• Volume: 9
• Issue: 1
• Start Page: 359
• End Page: 359
• Grant/Funding Information: This work was supported by the Institute of Biomedical Sciences, Georgia State University and by grants R01AI101047, R01AI116835, and R01AI093772 from US National Institutes of Health/National Institute of Allergy and Infectious Diseases.
• Keywords: Multidisciplinary Sciences; VACCINES; MONOCLONAL-ANTIBODY; MATRIX PROTEIN-2; HEMAGGLUTININ-STEM; Science & Technology; Science & Technology - Other Topics; DOMAIN; IN-VIVO; VACCINATION; ESCHERICHIA-COLI; HUMAN INFECTION; IMMUNE-RESPONSES
• Research Categories: Biology, Virology; Biology, Microbiology

Abstract

Current influenza vaccines provide limited protection against circulating influenza A viruses. A universal influenza vaccine will eliminate the intrinsic limitations of the seasonal flu vaccines. Here we report methodology to generate double-layered protein nanoparticles as a universal influenza vaccine. Layered nanoparticles are fabricated by desolvating tetrameric M2e into protein nanoparticle cores and coating these cores by crosslinking headless HAs. Representative headless HAs of two HA phylogenetic groups are constructed and purified. Vaccinations with the resulting protein nanoparticles in mice induces robust long-lasting immunity, fully protecting the mice against challenges by divergent influenza A viruses of the same group or both groups. The results demonstrate the importance of incorporating both structure-stabilized HA stalk domains and M2e into a universal influenza vaccine to improve its protective potency and breadth. These potent disassemblable protein nanoparticles indicate a wide application in protein drug delivery and controlled release.