Tomato bushy stunt virus (TBSV), a versatile platform for polyvalent display of antigenic epitopes and vaccine design

Shantanu Kumar; Wendy Ochoa; Pratik Singh; Catherine Hsu; Anette Schneemann; Marianne Manchester; Mark Olson; Vijay Reddy

doi:10.1016/j.virol.2009.02.051

Tomato bushy stunt virus (TBSV), a versatile platform for polyvalent display of antigenic epitopes and vaccine design

Shantanu Kumar, Wendy Ochoa, Pratik Singh, Catherine Hsu, Anette Schneemann, Marianne Manchester, Mark Olson, Vijay Reddy

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

34 Scopus citations

Abstract

Viruses-like particles (VLPs) are frequently being used as platforms for polyvalent display of foreign epitopes of interest on their capsid surface to improve their presentation enhancing the antigenicity and host immune response. In the present study, we used the VLPs of Tomato bushy stunt virus (TBSV), an icosahedral plant virus, as a platform to display 180 copies of 16 amino acid epitopes of ricin toxin fused to the C-terminal end of a modified TBSV capsid protein (NΔ52). Expression of the chimeric recombinant protein in insect cells resulted in spontaneous assembly of VLPs displaying the ricin epitope. Cryo-electron microscopy and image reconstruction of the chimeric VLPs at 22 Å resolution revealed the locations and orientation of the ricin epitope exposed on the TBSV capsid surface. Furthermore, injection of chimeric VLPs into mice generated antisera that detected the native ricin toxin. The ease of fusing of short peptides of 15-20 residues and their ability to form two kinds (T = 1, T = 3) of bio-nanoparticles that result in the display of 60 or 180 copies of less constrained and highly exposed antigenic epitopes makes TBSV an attractive and versatile display platform for vaccine design.

Original language	English (US)
Pages (from-to)	185-190
Number of pages	6
Journal	Virology
Volume	388
Issue number	1
DOIs	https://doi.org/10.1016/j.virol.2009.02.051
State	Published - May 25 2009
Externally published	Yes

Bibliographical note

Funding Information:
The authors would like to thank Professor Glen Nemerow and Dr. Sangita Venkataraman for carefully going through the manuscript and for helpful suggestions. The authors are extremely grateful to Drs. Jack Morris and Feng Qu of University of Nebraska, Lincoln, Nebraska for the cDNA clones of TBSV. The authors also like to thank Dr. H.B. Scholthof (Texas A&M University, College Station, TX) for the gift of native TBSV particles. The work reported in this manuscript was fully supported by a contract, W81XWH-04-2-0027 from U.S. Army to V.S.R.

Keywords

Capsid display
Ricin vaccine
Tomato bushy stunt virus
Vaccine design
Virus-like particles

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10.1016/j.virol.2009.02.051

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title = "Tomato bushy stunt virus (TBSV), a versatile platform for polyvalent display of antigenic epitopes and vaccine design",

abstract = "Viruses-like particles (VLPs) are frequently being used as platforms for polyvalent display of foreign epitopes of interest on their capsid surface to improve their presentation enhancing the antigenicity and host immune response. In the present study, we used the VLPs of Tomato bushy stunt virus (TBSV), an icosahedral plant virus, as a platform to display 180 copies of 16 amino acid epitopes of ricin toxin fused to the C-terminal end of a modified TBSV capsid protein (NΔ52). Expression of the chimeric recombinant protein in insect cells resulted in spontaneous assembly of VLPs displaying the ricin epitope. Cryo-electron microscopy and image reconstruction of the chimeric VLPs at 22 {\AA} resolution revealed the locations and orientation of the ricin epitope exposed on the TBSV capsid surface. Furthermore, injection of chimeric VLPs into mice generated antisera that detected the native ricin toxin. The ease of fusing of short peptides of 15-20 residues and their ability to form two kinds (T = 1, T = 3) of bio-nanoparticles that result in the display of 60 or 180 copies of less constrained and highly exposed antigenic epitopes makes TBSV an attractive and versatile display platform for vaccine design.",

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author = "Shantanu Kumar and Wendy Ochoa and Pratik Singh and Catherine Hsu and Anette Schneemann and Marianne Manchester and Mark Olson and Vijay Reddy",

note = "Funding Information: The authors would like to thank Professor Glen Nemerow and Dr. Sangita Venkataraman for carefully going through the manuscript and for helpful suggestions. The authors are extremely grateful to Drs. Jack Morris and Feng Qu of University of Nebraska, Lincoln, Nebraska for the cDNA clones of TBSV. The authors also like to thank Dr. H.B. Scholthof (Texas A\&M University, College Station, TX) for the gift of native TBSV particles. The work reported in this manuscript was fully supported by a contract, W81XWH-04-2-0027 from U.S. Army to V.S.R. ",

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AU - Hsu, Catherine

AU - Schneemann, Anette

AU - Manchester, Marianne

AU - Olson, Mark

AU - Reddy, Vijay

N1 - Funding Information: The authors would like to thank Professor Glen Nemerow and Dr. Sangita Venkataraman for carefully going through the manuscript and for helpful suggestions. The authors are extremely grateful to Drs. Jack Morris and Feng Qu of University of Nebraska, Lincoln, Nebraska for the cDNA clones of TBSV. The authors also like to thank Dr. H.B. Scholthof (Texas A&M University, College Station, TX) for the gift of native TBSV particles. The work reported in this manuscript was fully supported by a contract, W81XWH-04-2-0027 from U.S. Army to V.S.R.

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N2 - Viruses-like particles (VLPs) are frequently being used as platforms for polyvalent display of foreign epitopes of interest on their capsid surface to improve their presentation enhancing the antigenicity and host immune response. In the present study, we used the VLPs of Tomato bushy stunt virus (TBSV), an icosahedral plant virus, as a platform to display 180 copies of 16 amino acid epitopes of ricin toxin fused to the C-terminal end of a modified TBSV capsid protein (NΔ52). Expression of the chimeric recombinant protein in insect cells resulted in spontaneous assembly of VLPs displaying the ricin epitope. Cryo-electron microscopy and image reconstruction of the chimeric VLPs at 22 Å resolution revealed the locations and orientation of the ricin epitope exposed on the TBSV capsid surface. Furthermore, injection of chimeric VLPs into mice generated antisera that detected the native ricin toxin. The ease of fusing of short peptides of 15-20 residues and their ability to form two kinds (T = 1, T = 3) of bio-nanoparticles that result in the display of 60 or 180 copies of less constrained and highly exposed antigenic epitopes makes TBSV an attractive and versatile display platform for vaccine design.

AB - Viruses-like particles (VLPs) are frequently being used as platforms for polyvalent display of foreign epitopes of interest on their capsid surface to improve their presentation enhancing the antigenicity and host immune response. In the present study, we used the VLPs of Tomato bushy stunt virus (TBSV), an icosahedral plant virus, as a platform to display 180 copies of 16 amino acid epitopes of ricin toxin fused to the C-terminal end of a modified TBSV capsid protein (NΔ52). Expression of the chimeric recombinant protein in insect cells resulted in spontaneous assembly of VLPs displaying the ricin epitope. Cryo-electron microscopy and image reconstruction of the chimeric VLPs at 22 Å resolution revealed the locations and orientation of the ricin epitope exposed on the TBSV capsid surface. Furthermore, injection of chimeric VLPs into mice generated antisera that detected the native ricin toxin. The ease of fusing of short peptides of 15-20 residues and their ability to form two kinds (T = 1, T = 3) of bio-nanoparticles that result in the display of 60 or 180 copies of less constrained and highly exposed antigenic epitopes makes TBSV an attractive and versatile display platform for vaccine design.

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ER -

Tomato bushy stunt virus (TBSV), a versatile platform for polyvalent display of antigenic epitopes and vaccine design

Abstract

Bibliographical note

Keywords

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