title: A rationally designed form of the TLR5 agonist, flagellin, supports superior immunogenicity of Influenza B globular head vaccines.
abstract: Previously, we demonstrated that for H1N1 and H5N1 influenza strains, the globular head of the hemagglutinin (HA) antigen fused to flagellin of Salmonella typhimurium fljB (STF2) is highly immunogenic in preclinical models and man (Song et al. (2008) [13]; Song et al. (2009) [14]; Taylor et al. (2012) [12]). Further we showed that the vaccine format, or point of attachment of the vaccine antigen to flagellin, can dramatically affect the immunogenicity and safety profile of the vaccine. However, Influenza B vaccines based on these formats are poor triggers of TLR5 and consequently are poorly immunogenic. Through rational design, here we show that we have identified a fusion position within domain 3 of flagellin that improves TLR5 signaling and consequently, immunogenicity of multiple influenza B vaccines. Our results demonstrate that, similar to influenza A strains, the protective subunit of the influenza B HA can be fused to flagellin and produced in a standard prokaryotic expression system thereby allowing for cost and time efficient production of multivalent seasonal influenza vaccines.
authors.affiliation: VaxInnate Corporation, 3 Cedar Brook Drive, Cranbury, NJ 08512-0026, USA. Electronic address: langzhou.song@vaxinnate.com.
authors.forename: Langzhou
authors.initials: L
authors.lastname: Song
authors.affiliation: VaxInnate Corporation, 3 Cedar Brook Drive, Cranbury, NJ 08512-0026, USA.
authors.forename: Ge
authors.initials: G
authors.lastname: Liu
authors.affiliation: VaxInnate Corporation, 3 Cedar Brook Drive, Cranbury, NJ 08512-0026, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Umlauf
authors.affiliation: VaxInnate Corporation, 3 Cedar Brook Drive, Cranbury, NJ 08512-0026, USA.
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Liu
authors.affiliation: VaxInnate Corporation, 3 Cedar Brook Drive, Cranbury, NJ 08512-0026, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.affiliation: VaxInnate Corporation, 3 Cedar Brook Drive, Cranbury, NJ 08512-0026, USA.
authors.forename: Haijun
authors.initials: H
authors.lastname: Tian
authors.affiliation: VaxInnate Corporation, 3 Cedar Brook Drive, Cranbury, NJ 08512-0026, USA.
authors.forename: Lucia
authors.initials: L
authors.lastname: Reiserova
authors.affiliation: VaxInnate Corporation, 3 Cedar Brook Drive, Cranbury, NJ 08512-0026, USA.
authors.forename: Fuxiang
authors.initials: F
authors.lastname: Hou
authors.affiliation: VaxInnate Corporation, 3 Cedar Brook Drive, Cranbury, NJ 08512-0026, USA.
authors.forename: Rodney
authors.initials: R
authors.lastname: Bell
authors.affiliation: VaxInnate Corporation, 3 Cedar Brook Drive, Cranbury, NJ 08512-0026, USA.
authors.forename: Lynda
authors.initials: L
authors.lastname: Tussey
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D005260:Female; D005408:Flagellin / Q000276:immunology*; D006385:Hemagglutination Inhibition Tests; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D009981:Influenza B virus / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D009976:Orthomyxoviridae Infections / Q000517:prevention & control; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000276:immunology; D051198:Toll-Like Receptor 5 / Q000819:agonists* / Q000276:immunology
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D011993:Recombinant Fusion Proteins; D051198:Toll-Like Receptor 5; D005408:Flagellin
keywords: Flagellin domain 3 insertion; HA globular head; Influenza B vaccine