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

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. - Highlights: • Stable protein nanoparticles can be fabricated using DTSSP crosslinker. • Protein nanoparticles induce strong antibody responses against M2e and HA stalk domains in mice. • Vaccinated mice are fully protected againstmore » lethal dose of influenza A virus challenges.« less

Authors:
 [1];  [2];  [3];  [2];  [1];  [3];  [1]
  1. Center for Inflammation, Immunity & Infection, Georgia State University Institute for Biomedical Sciences, Atlanta, GA (United States)
  2. Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA (United States)
  3. Georgia Institute of Technology, School of Chemical & Biomolecular Engineering, Atlanta, GA (United States)
Publication Date:
OSTI Identifier:
22722964
Resource Type:
Journal Article
Journal Name:
Virology
Additional Journal Information:
Journal Volume: 509; Other Information: Copyright (c) 2017 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0042-6822
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANTIGENS; CARRIERS; INFLUENZA VIRUSES; LETHAL DOSES; MATRICES; MICE; NANOPARTICLES; SAFETY; VACCINES

Citation Formats

Deng, Lei, Kim, Jong R., Chang, Timothy Z., Zhang, Han, Mohan, Teena, Champion, Julie A., and Wang, Bao-Zhong. Protein nanoparticle vaccine based on flagellin carrier fused to influenza conserved epitopes confers full protection against influenza A virus challenge. United States: N. p., 2017. Web. doi:10.1016/J.VIROL.2017.06.001.
Deng, Lei, Kim, Jong R., Chang, Timothy Z., Zhang, Han, Mohan, Teena, Champion, Julie A., & Wang, Bao-Zhong. Protein nanoparticle vaccine based on flagellin carrier fused to influenza conserved epitopes confers full protection against influenza A virus challenge. United States. doi:10.1016/J.VIROL.2017.06.001.
Deng, Lei, Kim, Jong R., Chang, Timothy Z., Zhang, Han, Mohan, Teena, Champion, Julie A., and Wang, Bao-Zhong. Fri . "Protein nanoparticle vaccine based on flagellin carrier fused to influenza conserved epitopes confers full protection against influenza A virus challenge". United States. doi:10.1016/J.VIROL.2017.06.001.
@article{osti_22722964,
title = {Protein nanoparticle vaccine based on flagellin carrier fused to influenza conserved epitopes confers full protection against influenza A virus challenge},
author = {Deng, Lei and Kim, Jong R. and Chang, Timothy Z. and Zhang, Han and Mohan, Teena and Champion, Julie A. and Wang, Bao-Zhong},
abstractNote = {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. - Highlights: • Stable protein nanoparticles can be fabricated using DTSSP crosslinker. • Protein nanoparticles induce strong antibody responses against M2e and HA stalk domains in mice. • Vaccinated mice are fully protected against lethal dose of influenza A virus challenges.},
doi = {10.1016/J.VIROL.2017.06.001},
journal = {Virology},
issn = {0042-6822},
number = ,
volume = 509,
place = {United States},
year = {2017},
month = {9}
}