title: A bivalent influenza VLP vaccine confers complete inhibition of virus replication in lungs.
abstract: The conventional egg-grown influenza vaccines are trivalent. To test the feasibility of using multivalent influenza virus-like particles (VLPs) as an alternative influenza vaccine, we developed cell-derived influenza VLPs containing the hemagglutinin (HA) of the H1 subtype virus A/PR/8/34 or the H3 subtype virus A/Aichi/2/68 (X31). Mice immunized intramuscularly with bivalent influenza VLPs containing H1 and H3 HAs induced neutralizing activities against the homologous and closely related H1N1 strains A/PR/8/34 and A/WSN/33 as well as the H3N2 strains A/Aichi/2/68 (X31) and A/Hong Kong/68, but not the A/Philippines/2/82 strain isolated 14 years later. HA sequence and structure analysis indicated that antigenic distance could be a major factor in predicting cross-protection by VLP vaccines. The bivalent influenza VLP vaccine demonstrated advantages in broadening the protective immunity after lethal challenge infections when compared to a monovalent influenza VLP vaccine. High levels of the inflammatory cytokine IL-6 were observed in naïve or unprotected immunized mice but not in protected mice upon lethal challenge. These results indicate that multivalent influenza VLP vaccines can be an effective antigen for developing safe and alternative vaccine to control the spread of influenza viruses.
authors.affiliation: Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors.forename: Fu Shi
authors.initials: FS
authors.lastname: Quan
authors.forename: David
authors.initials: D
authors.lastname: Steinhauer
authors.forename: Chunzi
authors.initials: C
authors.lastname: Huang
authors.forename: Ted M
authors.initials: TM
authors.lastname: Ross
authors.forename: Richard W
authors.initials: RW
authors.lastname: Compans
authors.forename: Sang-Moo
authors.initials: SM
authors.lastname: Kang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D001835:Body Weight; D005260:Female; D006389:Hemagglutinins, Viral / Q000276:immunology; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D015850:Interleukin-6 / Q000032:analysis; D008168:Lung / Q000276:immunology / Q000821:virology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D009976:Orthomyxoviridae Infections / Q000517:prevention & control*; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D016019:Survival Analysis; D010948:Viral Plaque Assay; D022701:Virosomes / Q000276:immunology*; D014779:Virus Replication
chemical_list: D000914:Antibodies, Viral; D006389:Hemagglutinins, Viral; D007252:Influenza Vaccines; D015850:Interleukin-6; D022701:Virosomes; C458881:hemagglutinin fusogenic peptide, influenza virus