title: Plant virus particles carrying tumour antigen activate TLR7 and Induce high levels of protective antibody.
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-α 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.
authors.affiliation: Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
authors.forename: Jantipa
authors.initials: J
authors.lastname: Jobsri
authors.affiliation: Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
authors.forename: Alex
authors.initials: A
authors.lastname: Allen
authors.affiliation: King's College London, Peter Gorer Department of Immunobiology, Guy's Hospital, London, United Kingdom.
authors.forename: Deepa
authors.initials: D
authors.lastname: Rajagopal
authors.affiliation: Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
authors.forename: Michael
authors.initials: M
authors.lastname: Shipton
authors.affiliation: Plant Biology and Crop Science Department, Rothamsted Research, Harpenden, United Kingdom.
authors.forename: Kostya
authors.initials: K
authors.lastname: Kanyuka
authors.affiliation: Department of Biological Chemistry, John Innes Centre, Norwich, United Kingdom.
authors.forename: George P
authors.initials: GP
authors.lastname: Lomonossoff
authors.affiliation: Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
authors.forename: Christian
authors.initials: C
authors.lastname: Ottensmeier
authors.affiliation: King's College London, Peter Gorer Department of Immunobiology, Guy's Hospital, London, United Kingdom.
authors.forename: Sandra S
authors.initials: SS
authors.lastname: Diebold
authors.affiliation: Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
authors.forename: Freda K
authors.initials: FK
authors.lastname: Stevenson
authors.affiliation: Cancer Sciences Unit, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
authors.forename: Natalia
authors.initials: N
authors.lastname: Savelyeva
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D003713:Dendritic Cells; D005260:Female; D007074:Immunoglobulin G / Q000276:immunology; D018664:Interleukin-12 / Q000378:metabolism; D008223:Lymphoma; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010942:Plant Viruses / Q000276:immunology*; D014026:Nicotiana / Q000821:virology; D051199:Toll-Like Receptor 7 / Q000235:genetics / Q000378:metabolism*; D014771:Virion / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D007074:Immunoglobulin G; D051199:Toll-Like Receptor 7; D018664:Interleukin-12