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Plant virus particles carrying tumour antigen activate TLR7 and induce high levels of protective antibody

Plant virus particles carrying tumour antigen activate TLR7 and induce high levels of protective antibody
Plant virus particles carrying tumour antigen activate TLR7 and induce high levels of protective antibody
Induction of potent antibody is the goal of many vaccines targeted against infections or cancer. Modern vaccine designs that use virus-like particles (VLP) have shown efficacy for prophylactic vaccination against virus-associated cancer in the clinic. Here we used plant viral particles (PVP), which are structurally analogous to VLP, coupled to a weak idiotypic (Id) tumour antigen, as a conjugate vaccine to induce antibody against a murine B-cell malignancy. The Id-PVP vaccine incorporates a natural adjuvant, the viral ssRNA, which acts via TLR7. It induced potent protective anti-Id antibody responses in an in vivo mouse model, superior to the "gold standard" Id vaccine, with prevalence of the IgG2a isotype. Combination with alum further increased antibody levels and maintained the IgG2a bias. Engagement of TLR7 in vivo was followed by secretion of IFN-? by plasmacytoid dendritic cells and by activation of splenic CD11chi conventional dendritic cells. The latter was apparent from up-regulation of co-stimulatory molecules and from secretion of a wide range of inflammatory cytokines and chemokines including the Th1-governing cytokine IL-12, in keeping with the IgG2a antibody isotype distribution. PVP conjugates are a novel cancer vaccine design, offering an attractive molecular form, similar to VLP, and providing T-cell help. In contrast to VLP, they also incorporate a safe "in-built" ssRNA adjuvant.
1932-6203
1-16
Jobsri, Jantipa
fcffeef7-8d3e-4a78-a258-fb5502a01fba
Allen, Alex
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Rajagopal, Deepa
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Shipton, Michael
9225574d-190e-41fb-8639-ff784ba63fe6
Kanyuka, Kostya
542d1257-2907-4a34-a024-6817fd44b838
Lomonossoff, George P.
896bab6a-3c0c-48e6-9e46-7db6314bbcb6
Ottensmeier, Christian
42b8a398-baac-4843-a3d6-056225675797
Diebold, Sandra S
749995df-ab42-424a-8e12-b68c2c4bd2b1
Stevenson, Freda K.
ba803747-c0ac-409f-a9c2-b61fde009f8c
Savelyeva, Natalia
804c3e15-d260-4717-9b7c-15c16ba87fc7
Jobsri, Jantipa
fcffeef7-8d3e-4a78-a258-fb5502a01fba
Allen, Alex
acab9114-885e-4a11-b88d-163703629f80
Rajagopal, Deepa
d790f5d0-4639-4783-bab8-8ad646a36331
Shipton, Michael
9225574d-190e-41fb-8639-ff784ba63fe6
Kanyuka, Kostya
542d1257-2907-4a34-a024-6817fd44b838
Lomonossoff, George P.
896bab6a-3c0c-48e6-9e46-7db6314bbcb6
Ottensmeier, Christian
42b8a398-baac-4843-a3d6-056225675797
Diebold, Sandra S
749995df-ab42-424a-8e12-b68c2c4bd2b1
Stevenson, Freda K.
ba803747-c0ac-409f-a9c2-b61fde009f8c
Savelyeva, Natalia
804c3e15-d260-4717-9b7c-15c16ba87fc7

Jobsri, Jantipa, Allen, Alex, Rajagopal, Deepa, Shipton, Michael, Kanyuka, Kostya, Lomonossoff, George P., Ottensmeier, Christian, Diebold, Sandra S, Stevenson, Freda K. and Savelyeva, Natalia (2015) Plant virus particles carrying tumour antigen activate TLR7 and induce high levels of protective antibody. PLoS ONE, 10 (2), 1-16, [e0118096]. (doi:10.1371/journal.pone.0118096). (PMID:25692288)

Record type: Article

Abstract

Induction of potent antibody is the goal of many vaccines targeted against infections or cancer. Modern vaccine designs that use virus-like particles (VLP) have shown efficacy for prophylactic vaccination against virus-associated cancer in the clinic. Here we used plant viral particles (PVP), which are structurally analogous to VLP, coupled to a weak idiotypic (Id) tumour antigen, as a conjugate vaccine to induce antibody against a murine B-cell malignancy. The Id-PVP vaccine incorporates a natural adjuvant, the viral ssRNA, which acts via TLR7. It induced potent protective anti-Id antibody responses in an in vivo mouse model, superior to the "gold standard" Id vaccine, with prevalence of the IgG2a isotype. Combination with alum further increased antibody levels and maintained the IgG2a bias. Engagement of TLR7 in vivo was followed by secretion of IFN-? by plasmacytoid dendritic cells and by activation of splenic CD11chi conventional dendritic cells. The latter was apparent from up-regulation of co-stimulatory molecules and from secretion of a wide range of inflammatory cytokines and chemokines including the Th1-governing cytokine IL-12, in keeping with the IgG2a antibody isotype distribution. PVP conjugates are a novel cancer vaccine design, offering an attractive molecular form, similar to VLP, and providing T-cell help. In contrast to VLP, they also incorporate a safe "in-built" ssRNA adjuvant.

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More information

Accepted/In Press date: 6 January 2015
e-pub ahead of print date: 18 February 2015
Published date: 18 February 2015
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 396333
URI: http://eprints.soton.ac.uk/id/eprint/396333
ISSN: 1932-6203
PURE UUID: 75ece385-2ae2-424b-88b3-5342f81370b4
ORCID for Freda K. Stevenson: ORCID iD orcid.org/0000-0002-0933-5021

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Date deposited: 08 Jun 2016 10:09
Last modified: 15 Mar 2024 02:53

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Contributors

Author: Jantipa Jobsri
Author: Alex Allen
Author: Deepa Rajagopal
Author: Michael Shipton
Author: Kostya Kanyuka
Author: George P. Lomonossoff
Author: Sandra S Diebold

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