Superior efficacy of a recombinant flagellin:H5N1 HA globular head vaccine is determined by the placement of the globular head within flagellin

Langzhou Song; Yi Zhang; Nadezhda E. Yun; Allison L. Poussard; Jeanon N. Smith; Jennifer K. Smith; Viktoriya Borisevich; Jenna J. Linde; Michele A. Zacks; Hong Li; Uma Kavita; Lucia Reiserova; Xiangyu Liu; Kunmi Dumuren; Bhuvaneswari Balasubramanian; Bruce Weaver; Jason Parent; Scott Umlauf; Ge Liu; Jim Huleatt; Lynda Tussey; Slobodan Paessler

doi:10.1016/j.vaccine.2009.07.060

Superior efficacy of a recombinant flagellin:H5N1 HA globular head vaccine is determined by the placement of the globular head within flagellin

Langzhou Song, Yi Zhang, Nadezhda E. Yun, Allison L. Poussard, Jeanon N. Smith, Jennifer K. Smith, Viktoriya Borisevich, Jenna J. Linde, Michele A. Zacks, Hong Li, Uma Kavita, Lucia Reiserova, Xiangyu Liu, Kunmi Dumuren, Bhuvaneswari Balasubramanian, Bruce Weaver, Jason Parent, Scott Umlauf, Ge Liu, Jim HuleattLynda Tussey, Slobodan Paessler

Pathology

Research output: Contribution to journal › Article › peer-review

73 Scopus citations

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.

Original language	English (US)
Pages (from-to)	5875-5884
Number of pages	10
Journal	Vaccine
Volume	27
Issue number	42
DOIs	https://doi.org/10.1016/j.vaccine.2009.07.060
State	Published - Sep 25 2009

Keywords

Avian flu vaccine
HA globular head
Prokaryotic production

ASJC Scopus subject areas

Molecular Medicine
General Immunology and Microbiology
General Veterinary
Public Health, Environmental and Occupational Health
Infectious Diseases

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10.1016/j.vaccine.2009.07.060

Cite this

Song, L., Zhang, Y., Yun, N. E., Poussard, A. L., Smith, J. N., Smith, J. K., Borisevich, V., Linde, J. J., Zacks, M. A., Li, H., Kavita, U., Reiserova, L., Liu, X., Dumuren, K., Balasubramanian, B., Weaver, B., Parent, J., Umlauf, S., Liu, G., ... Paessler, S. (2009). Superior efficacy of a recombinant flagellin:H5N1 HA globular head vaccine is determined by the placement of the globular head within flagellin. Vaccine, 27(42), 5875-5884. https://doi.org/10.1016/j.vaccine.2009.07.060

Song, L, Zhang, Y, Yun, NE, Poussard, AL, Smith, JN, Smith, JK, Borisevich, V, Linde, JJ, Zacks, MA, Li, H, Kavita, U, Reiserova, L, Liu, X, Dumuren, K, Balasubramanian, B, Weaver, B, Parent, J, Umlauf, S, Liu, G, Huleatt, J, Tussey, L & Paessler, S 2009, 'Superior efficacy of a recombinant flagellin:H5N1 HA globular head vaccine is determined by the placement of the globular head within flagellin', Vaccine, vol. 27, no. 42, pp. 5875-5884. https://doi.org/10.1016/j.vaccine.2009.07.060

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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.",

keywords = "Avian flu vaccine, HA globular head, Prokaryotic production",

author = "Langzhou Song and Yi Zhang and Yun, {Nadezhda E.} and Poussard, {Allison L.} and Smith, {Jeanon N.} and Smith, {Jennifer K.} and Viktoriya Borisevich and Linde, {Jenna J.} and Zacks, {Michele A.} and Hong Li and Uma Kavita and Lucia Reiserova and Xiangyu Liu and Kunmi Dumuren and Bhuvaneswari Balasubramanian and Bruce Weaver and Jason Parent and Scott Umlauf and Ge Liu and Jim Huleatt and Lynda Tussey and Slobodan Paessler",

note = "Funding Information: We are grateful to Drs. Phil Wyde, Alan Shaw, Bob Becker and David Taylor for providing scientific input and technical training and to Jenna Linde for excellent data entry through the studies and for assistance in preparing the manuscript figures. We also thank Nathaniel Linde for technical assistance and Dr. Diana Noah and her team for performing the HAI assay at the BSL3 facility in Southern Research Institute. SP was supported by NIH K08 grant no. AI059491. Funding was provided by a grant from the Bill and Melinda Gates Foundation and VaxInnate Corporation.",

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AU - Song, Langzhou

AU - Zhang, Yi

AU - Yun, Nadezhda E.

AU - Poussard, Allison L.

AU - Smith, Jeanon N.

AU - Smith, Jennifer K.

AU - Borisevich, Viktoriya

AU - Linde, Jenna J.

AU - Zacks, Michele A.

AU - Li, Hong

AU - Kavita, Uma

AU - Reiserova, Lucia

AU - Liu, Xiangyu

AU - Dumuren, Kunmi

AU - Balasubramanian, Bhuvaneswari

AU - Weaver, Bruce

AU - Parent, Jason

AU - Umlauf, Scott

AU - Liu, Ge

AU - Huleatt, Jim

AU - Tussey, Lynda

AU - Paessler, Slobodan

N1 - Funding Information: We are grateful to Drs. Phil Wyde, Alan Shaw, Bob Becker and David Taylor for providing scientific input and technical training and to Jenna Linde for excellent data entry through the studies and for assistance in preparing the manuscript figures. We also thank Nathaniel Linde for technical assistance and Dr. Diana Noah and her team for performing the HAI assay at the BSL3 facility in Southern Research Institute. SP was supported by NIH K08 grant no. AI059491. Funding was provided by a grant from the Bill and Melinda Gates Foundation and VaxInnate Corporation.

PY - 2009/9/25

Y1 - 2009/9/25

N2 - 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.

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KW - HA globular head

KW - Prokaryotic production

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Superior efficacy of a recombinant flagellin:H5N1 HA globular head vaccine is determined by the placement of the globular head within flagellin

Abstract

Keywords

ASJC Scopus subject areas

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