title: A novel H6N1 virus-like particle vaccine induces long-lasting cross-clade antibody immunity against human and avian H6N1 viruses.
abstract: Avian influenza A(H6N1) virus is one of the most common viruses isolated from migrating birds and domestic poultry in many countries. The first and only known case of human infection by H6N1 virus in the world was reported in Taiwan in 2013. This led to concern that H6N1 virus may cause a threat to public health. In this study, we engineered a recombinant H6N1 virus-like particle (VLP) and investigated its vaccine effectiveness compared to the traditional egg-based whole inactivated virus (WIV) vaccine. The H6N1-VLPs exhibited similar morphology and functional characteristics to influenza viruses. Prime-boost intramuscular immunization in mice with unadjuvanted H6N1-VLPs were highly immunogenic and induced long-lasting antibody immunity. The functional activity of the VLP-elicited IgG antibodies was proved by in vitro seroprotective hemagglutination inhibition and microneutralization titers against the homologous human H6N1 virus, as well as in vivo viral challenge analyses which showed H6N1-VLP immunization significantly reduced viral load in the lung, and protected against human H6N1 virus infection. Of particular note, the H6N1-VLPs but not the H6N1-WIVs were able to confer cross-reactive humoral immunity; antibodies induced by H6N1-VLP vaccine robustly inhibited the hemagglutination activities and in vitro replication of distantly-related heterologous avian H6N1 viruses. Furthermore, the H6N1-VLPs were found to elicit significantly greater anti-HA2 antibody responses in immunized mice than H6N1-WIVs. Collectively, we demonstrated for the first time a novel H6N1-VLP vaccine that effectively provides broadly protective immunity against both human and avian H6N1 viruses. These results, which uncover the underlying mechanisms for induction of wide-range immunity against influenza viruses, may be useful for future influenza vaccine development.
authors.affiliation: Institute of Biotechnology, National Taiwan University, Taipei, Taiwan; Center for Research, Diagnostics and Vaccine Development, Centers for Disease Control, Taipei, Taiwan; Agricultural Biotechnology Research Center, Academia Sinica, Taiwan.
authors.forename: Ji-Rong
authors.initials: JR
authors.lastname: Yang
authors.affiliation: Center for Research, Diagnostics and Vaccine Development, Centers for Disease Control, Taipei, Taiwan.
authors.forename: Chih-Yuan
authors.initials: CY
authors.lastname: Chen
authors.affiliation: Center for Research, Diagnostics and Vaccine Development, Centers for Disease Control, Taipei, Taiwan.
authors.forename: Chuan-Yi
authors.initials: CY
authors.lastname: Kuo
authors.affiliation: Center for Research, Diagnostics and Vaccine Development, Centers for Disease Control, Taipei, Taiwan.
authors.forename: Chieh-Yu
authors.initials: CY
authors.lastname: Cheng
authors.affiliation: Animal Health Research Institute, Council of Agriculture, Taipei, Taiwan.
authors.forename: Min-Shiuh
authors.initials: MS
authors.lastname: Lee
authors.affiliation: Animal Health Research Institute, Council of Agriculture, Taipei, Taiwan.
authors.forename: Ming-Chu
authors.initials: MC
authors.lastname: Cheng
authors.affiliation: Agricultural Biotechnology Research Center, Academia Sinica, Taiwan.
authors.forename: Yu-Chih
authors.initials: YC
authors.lastname: Yang
authors.affiliation: Agricultural Biotechnology Research Center, Academia Sinica, Taiwan.
authors.forename: Chia-Ying
authors.initials: CY
authors.lastname: Wu
authors.affiliation: Center for Research, Diagnostics and Vaccine Development, Centers for Disease Control, Taipei, Taiwan; School of Medical Laboratory Science and Biotechnology, Taipei Medical University, Taipei, Taiwan.
authors.forename: Ho-Sheng
authors.initials: HS
authors.lastname: Wu
authors.affiliation: Center for Research, Diagnostics and Vaccine Development, Centers for Disease Control, Taipei, Taiwan. Electronic address: mtliu@cdc.gov.tw.
authors.forename: Ming-Tsan
authors.initials: MT
authors.lastname: Liu
authors.affiliation: Institute of Biotechnology, National Taiwan University, Taipei, Taiwan; Agricultural Biotechnology Research Center, Academia Sinica, Taiwan. Electronic address: pwhsiao@gate.sinica.edu.tw.
authors.forename: Pei-Wen
authors.initials: PW
authors.lastname: Hsiao
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology*; D001717:Birds; D003429:Cross Reactions / Q000276:immunology; D005260:Female; D006801:Humans; D009980:Influenza A virus / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology* / Q000494:pharmacology*; D005585:Influenza in Birds / Q000276:immunology / Q000821:virology; D007251:Influenza, Human / Q000276:immunology / Q000821:virology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins; D015164:Vaccines, Inactivated / Q000276:immunology / Q000494:pharmacology; D058425:Vaccines, Virus-Like Particle / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D007252:Influenza Vaccines; D011994:Recombinant Proteins; D015164:Vaccines, Inactivated; D058425:Vaccines, Virus-Like Particle
keywords: Broad-spectrum protective immunity; Influenza A (H6N1) virus; Virus-like particle vaccine