title: Superior efficacy of a recombinant flagellin:H5N1 HA globular head vaccine is determined by the placement of the globular head within flagellin.
abstract: Transmission of highly pathogenic avian influenza (HPAI) between birds and humans is an ongoing threat that holds potential for the emergence of a pandemic influenza strain. A major barrier to an effective vaccine against avian influenza has been the generally poor immunopotency of many of the HPAI strains coupled with the manufacturing constraints employing conventional methodologies. Fusion of flagellin, a toll-like receptor-5 ligand, to vaccine antigens has been shown to enhance the immune response to the fused antigen in preclinical studies. Here, we have evaluated the immunogenicity and efficacy of a panel of flagellin-based hemagglutinin (HA) globular head fusion vaccines in inbred mice. The HA globular head of these vaccines is derived from the A/Vietnam/1203/04 (VN04; H5N1) HA molecule. We find that replacement of domain D3 of flagellin with the VN04 HA globular head creates a highly effective vaccine that elicits protective HAI titers which protect mice against disease and death in a lethal challenge model.
authors: VaxInnate Corporation, 3 Cedar Brook Drive, Cranbury, NJ 08512-0026, USA. langzhou.song@vaxinnate.com
authors: Langzhou
authors: L
authors: Song
authors: Yi
authors: Y
authors: Zhang
authors: Nadezhda E
authors: NE
authors: Yun
authors: Allison L
authors: AL
authors: Poussard
authors: Jeanon N
authors: JN
authors: Smith
authors: Jennifer K
authors: JK
authors: Smith
authors: Viktoriya
authors: V
authors: Borisevich
authors: Jenna J
authors: JJ
authors: Linde
authors: Michele A
authors: MA
authors: Zacks
authors: Hong
authors: H
authors: Li
authors: Uma
authors: U
authors: Kavita
authors: Lucia
authors: L
authors: Reiserova
authors: Xiangyu
authors: X
authors: Liu
authors: Kunmi
authors: K
authors: Dumuren
authors: Bhuvaneswari
authors: B
authors: Balasubramanian
authors: Bruce
authors: B
authors: Weaver
authors: Jason
authors: J
authors: Parent
authors: Scott
authors: S
authors: Umlauf
authors: Ge
authors: G
authors: Liu
authors: Jim
authors: J
authors: Huleatt
authors: Lynda
authors: L
authors: Tussey
authors: Slobodan
authors: S
authors: Paessler
mesh_terms: D000818:Animals; D002460:Cell Line; D005260:Female; D005408:Flagellin / Q000276:immunology* / Q000378:metabolism; D006385:Hemagglutination Inhibition Tests; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology*; D006801:Humans; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control*; D011994:Recombinant Proteins / Q000276:immunology; D051198:Toll-Like Receptor 5 / Q000378:metabolism
chemical_list: D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D011994:Recombinant Proteins; D051198:Toll-Like Receptor 5; D005408:Flagellin