Superior efficacy of a recombinant flagellin:H5N1 HA globular head vaccine is determined by the placement of the globular head within flagellin.
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.
Song
Langzhou
L
VaxInnate Corporation, 3 Cedar Brook Drive, Cranbury, NJ 08512-0026, USA. langzhou.song@vaxinnate.com
Zhang
Yi
Y
Yun
Nadezhda E
NE
Poussard
Allison L
AL
Smith
Jeanon N
JN
Smith
Jennifer K
JK
Borisevich
Viktoriya
V
Linde
Jenna J
JJ
Zacks
Michele A
MA
Li
Hong
H
Kavita
Uma
U
Reiserova
Lucia
L
Liu
Xiangyu
X
Dumuren
Kunmi
K
Balasubramanian
Bhuvaneswari
B
Weaver
Bruce
B
Parent
Jason
J
Umlauf
Scott
S
Liu
Ge
G
Huleatt
Jim
J
Tussey
Lynda
L
Paessler
Slobodan
S
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
D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D011994:Recombinant Proteins; D051198:Toll-Like Receptor 5; D005408:Flagellin