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.

Plant viruses and bacteriophages for drug delivery in medicine and biotechnology

“…Conjugation of the Id epitope to PVX through biotin-streptavidin interactions allowed for a multivalent presentation of the epitope. The multivalent display alongside with immune-stimulation through toll-like receptor-7 activation based on the encapsidated ssRNA genome of PVX led to enhanced immune stimulation, increased production of anti-Id antibodies, and improved resistance to Id-expressing BCL1 lymphoma challenge when compared to Id-streptavidin alone [44]. …”

Virus‐based nanoparticles as platform technologies for modern vaccines

“…PVX has been modified with the idiotypic (Id) immunoglobulin from B-cell lymphomas, a weak tumor antigen. When administered to mice, Id-PVX induced high titers of anti-Id antibodies, which prolonged survival after lymphoma challenge 69 .…”

Cowpea Mosaic Virus Promotes Anti‐Tumor Activity and Immune Memory in a Mouse Ovarian Tumor Model

“…Immuno-based therapies tested in ovarian cancer include vaccines, immune checkpoint blockade and adoptive T cell therapy. [7][8][9] We previously showed that Cowpea mosaic virus (CPMV) can be used to generate VNPs (retaining the virus genomic RNA) or virus-like particles (VLPs) that lack the genomic RNA, and are thus termed empty CPMV (eCPMV) particles. [4] Although APCs are often present in both primary ovarian tumors and malignant ascites, including dendritic cells (DCs), tumor-associated macrophages (TAMs), tumor associated neutrophils (TANs), and myeloid progenitors, most of them have a pro-tumor, immunosuppressive phenotype.…”