Protein nanoparticle vaccine based on flagellin carrier fused to influenza conserved epitopes confers full protection against influenza A virus challenge

• Type of Material: Article
• Authors: Lei Deng, Georgia State University; Jong R. Kim, Emory University; Timothy Z. Chang, Georgia Institute of Technology; Han Zhang, Emory University; Teena Mohan, Georgia State University; Julie A. Champion, Georgia Institute of Technology; Baozhong Wang, Emory University
• Language: English
• Date: 2017-09-01
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2017 Elsevier Inc.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.virol.2017.06.001
• Title of Journal or Parent Work: Virology
• ISSN: 0042-6822
• Volume: 509
• Start Page: 82
• End Page: 89
• Grant/Funding Information: This research was supported by National Institutes of Health (NIH)/ National Institute of Allergy and Infectious Diseases (NIAID) Grant R01 AI101047.
• Keywords: ECTODOMAIN; Science & Technology; HEMAGGLUTININ-STEM; Influenza; M2E; MATRIX PROTEIN-2; IMMUNOGENICITY; ANTIBODY-RESPONSE; Vaccine; EXTRACELLULAR DOMAIN; Nanoparticle; Matrix protein 2 ectodomain; INFECTION; FUSION; Virology; Hemagglutinin; TOLL-LIKE RECEPTOR-5; Life Sciences & Biomedicine; Flagellin
• Research Categories: Biology, Microbiology; Health Sciences, Immunology

Abstract

Currently marketed influenza vaccines only confer protection against matching influenza virus strains. The influenza A composition of these vaccines needs to be annually updated. Vaccines that target conserved epitopes of influenza viruses would in principle offer broad cross-protection against influenza A viruses. In our study, we investigated the specific immune responses and protective efficacy of protein nanoparticles based on fusion proteins of flagellin carrier linked to conserved influenza epitopes. We designed fusion proteins by replacing the hyperimmunogenic region of flagellin (FliC) with four tandem copies of the ectodomain of matrix protein 2 (f4M2e), H1 HA2 domain (fHApr8) or H3 HA2 domain (fHAaichi). Protein nanoparticles fabricated from these fusion proteins by using DTSSP crosslinking retained Toll-like receptor 5 agonist activity of FliC. Intranasal immunization with f4M2e, f4M2e/fHApr8 or f4M2e/fHAaichi nanoparticles induced vaccine antigen-specific humoral immune responses. It was also found that the incorporation of the H1 HA2 domain into f4M2e/fHApr8 nanoparticles boosted M2e specific antibody responses. Immunized mice were fully protected against lethal doses of virus challenge.