An E7-based therapeutic vaccine protects mice against HPV16 associated cancer

A plant protein signal sequence improved humoral immune response to HPV prophylactic and therapeutic DNA vaccines

“…6,7,10,11 To optimize plant production yield, signal sequences can be used. They may serve to target products to specific compartments of the plant cell for accumulation, like the endoplasmic reticulum (very suitable for protein folding and assembly) from where the proteins can be secreted to the apoplast, offering a natural way to concentrate proteins.…”

Prime–boost therapeutic vaccination in mice with DNA/DNA or DNA/Fowlpox virus recombinants expressing the Human Papilloma Virus type 16 E6 and E7 mutated proteins fused to the coat protein of Potato virus X

“…CaSki cells, which contain multiple copies of the integrated HPV16 DNA genome, green monkey kidney (Vero) cells, and normal human lung fibroblasts (MRC-5 cells) were grown in Dulbecco's modified Eagle's medium supplemented with 10% calf serum, and 100 U/ml penicillin and 100 mg/ml streptomycin. TC-1 star (TC-1*), a clone of TC-1 cells (Venuti et al, 2009), generally used for challenge to test putative prophylactic or therapeutic vaccines in the preclinical mouse model, was selected for its 100% tumorigenicity in challenged mice. TC-1 cells are derived from primary epithelial cells of C57BL/6 mice, and cotransformed with the HPV16 E6 and E7 and by the activated c-Ha-ras oncogene (Lin et al, 1996).…”

Plant-based vaccines against viruses

“…Evidence of high-yield expression of H5 haemagglutinin-derived VLPs via transient expression [44] 10 million vaccine dose "rapid fire" milestone by Medicago Inc. in DARPA Blue Angel programme [50] Human clinical trial of plant-made H5N1 vaccine candidate [47] HA-only VLPs produced for H7N9 outbreak virus [54] Phase 1 trials of H1N1pdm and HPAI H5N1 HA-derived plant-made products [48] Testing of plant-made engineered soluble trimeric HA (H1N1pdm) in mice [58] Adjuvanting of monomeric H1N1pdm HA with SiO 2 and bis-(3′,5′)-cyclic dimeric guanosine monophosphate (c-di-GMP) [59] Emergency response influenza vaccine candidates made in South Africa [43] Conjugation of plant-made HA to TMV particles and successful testing in mice [60] Elicitation of neutralising Ab with elastin-like polypeptide fused with stabilised soluble trimer-forming H5N1 HA [61] Presentation of M2e epitope on surface of rTMV virions elicits protective immunity to homologous and heterologous challenge in mice [64] Papillomaviruses Proof of efficacy of a plant-made Cottontail rabbit and Rabbit oral papillomavirus vaccines [74,75] High yields of HPV-16 L1 and VLPs via agroinfiltration-mediated transient expression or via transplastomic expression [76,77] Transplastomic expression of capsomere-forming HPV-16 L1 fused with Escherichia coli LTB as a built-in adjuvant [78] Successful expression of HPV-8 and Bovine papillomavirus L1 VLPs in plants [79,80] Co-expression of HPV-16 L1 with E coli LTB and oral immunisation elicits increased intestinal mucosal IgA responses to L1 [90] High-yield plant transient expression of chimaeric L1::L2 VLPs and proof of increased breadth of immune response [91] rPVX CP fusion with L2 108-120 epitope yields well and elicits high-titre anti-L2 protein sera in mice [97] Plant production, scale-up and protective efficacy in mouse model of therapeutic E7GGG-LicKM fusion protein vaccine [85][86][87] Plant expressed HPV-16 L1 with C-terminal string of E6 and E7 T-cell epitopes is viable prophylactic/therapeutic vaccine candidate [98] Production and proof of efficacy in mice of soluble E7GGG therapeutic vaccine in transplastomic Chlamydomonas reinhardtii [100] Proof of yield increase and eff...…”