Mutants of plant genes for developing cancer vaccines

Massa, Silvia; Paolini, Francesca; Spanó, Laura; Franconi, Rosella; Venuti, Aldo

doi:10.4161/hv.7.0.14577

Cited by 13 publications

(20 citation statements)

References 33 publications

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“…One approach we used to improve HPV immuno-therapy was to 're-invent' vaccine design using sequences of plant origin as tools for immune function enhancement. [6][7][8] Indeed, in the context of DNA vaccination, our first strategy was to fuse an attenuated HPV16 E7 gene to the PVX CP sequence, a carrier capable of generating CD4C T cell responses that may enhance CD8C T cell priming, This fusion construct was able to inhibit the growth of a HPVexpressing experimental mouse tumor. 7 Plants (whole plants, plant-derived organ cultures and cell cultures) can address low-cost, high quality/safe production of proteins including antigens.…”

Section: Introductionmentioning

confidence: 99%

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

Massa

Paolini²,

Curzio³

et al. 2017

Human Vaccines & Immunotherapeutics

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Signal sequences (ss) play a critical role in the sorting of nascent secretory and membrane proteins. This function has been conserved from bacteria through eukaryotes, although ss appear diverse in length and amino acid composition. Sorting of proteins is also critical to instruct antigens for a proper immunological response. Thus, a plant ss was used to drive Human Papillomavirus (HPV) model antigens into the human secretory pathway: the HPV16 E7 oncoprotein, its chimera with the coat protein (CP) of the Potato Virus X (PVX), the first 200 amino acids of the HPV16 minor capsid protein L2 (known to harbour cross-reacting epitopes) and its chimera with E7 gene. These genes were used to transfect HEK-293 cells and to immunize C57BL/6 mice. The ss-provided genes were expressed, and proteins detected by immunofluorescence and immunoblotting. Mouse immunization with DNA constructs carrying the ss elicited a strong humoral response against both E7 and L2 and a weak cell-mediated immunity.To our knowledge this is the first demonstration that a signal sequence derived from a plant can modulate the sorting of a heterologous protein in mammalian cells. This activity in mammalian cells may be responsible for the observed increased humoral response to DNA-based vaccines that are generally weak inducers of IgG response. This might open new perspectives in the design of DNA vaccines, especially to counteract infections where a strong humoral response is needed.

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Section: Introductionmentioning

confidence: 99%

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

Massa

Paolini²,

Curzio³

et al. 2017

Human Vaccines & Immunotherapeutics

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“…Given the advantages of mucosal vaccine delivered by aerosol, this way of immunization with recombinant avipoxvirus-based vaccines might improve immunogenicity and protection. Administration by the intratumoral route to deliver the transgenes directly into the tumor mass and fusion to the already tested adjuvants, such as the detoxified form of the saporin plant enzyme SAP-KQ (Massa et al, 2011), might also ameliorate immunogenicity and efficacy. CEFs and Vero, MRC-5, and NIH-3T3 cells were infected with the FP-E6F47RCP (2B, 1b-4b) and FP-E7GGGCP (2B, 1c-4c) recombinants to determine the intracellular localization of the transgene products.…”

Section: Discussionmentioning

confidence: 99%

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

Illiano

Bissa

Paolini³

et al. 2016

Virus Research

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Highlights FP-E6F47RCP and FP-E7GGGCP correctly express transgenes in different cell lines  After the genetic immunization, tumor volume was lower than in the control mice  Genetic immunization delayed tumor appearance compared to control mice  After DNA/FP vaccination, better results were obtained by E6/E7 single immunogens AbstractThe therapeutic antitumor potency of a prime-boost vaccination strategy was explored, based on the mutated, nontransforming forms of the E6 (E6F47R) and E7 (E7GGG) oncogenes of Human Papilloma Virus type 16 (HPV16), fused to the Potato virus X (PVX) coat protein (CP) sequence. Previous data showed that CP fusion improves the immunogenicity of tumor-associated antigens and may thus increase their efficacy.After verifying the correct expression of E6F47RCP and E7GGGCP inserted into DNA and Fowlpox virus recombinants by Western blotting and immunofluorescence, their combined use was evaluated for therapy in a pre-clinical mouse model of HPV16-related tumorigenicity. Immunization protocols were applied using homologous (DNA/DNA) or heterologous (DNA/Fowlpox) prime-boost vaccine regimens. The humoral 3 immune responses were determined by ELISA, and the therapeutic efficacy evaluated by the delay in tumor appearance and reduced tumor volume after inoculation of syngeneic TC-1* tumor cells. Homologous DNA/DNA genetic vaccines were able to better delay tumor appearance and inhibit tumor growth when DNAE6F47RCP and DNAE7GGGCP were administered in combination. However, the heterologous DNA/Fowlpox vaccination strategy was able to delay tumor appearance in a higher number of animals when E6F47RCP and in particular E7GGGCP were administered alone.

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“…116,117 Additionally, antigen-fusion constructs, whereby the antigen of interest is linked to a "carrier protein," can increase the immune visibility of the vaccine, and enhance DNA vaccine potency. [118][119][120] A major advantage of DNA vaccination is the ability of multiple molecules such as molecular adjuvants to be inserted into the plasmid. Unlike the addition of recombinant cytokines, costimulatory molecules, and TLR ligands, which have a limited duration due to the short half-life of recombinant protein in vivo, molecular adjuvant-encoding plasmids will express protein for the same duration as the antigen, stimulating the immune system for a greater length of time.…”

Section: Plasmid-encoded Cytokinesmentioning

confidence: 99%

Advancements in DNA vaccine vectors, non-mechanical delivery methods, and molecular adjuvants to increase immunogenicity

Suschak

Williams

Schmaljohn

2017

Human Vaccines & Immunotherapeutics

203

181

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A major advantage of DNA vaccination is the ability to induce both humoral and cellular immune responses. DNA vaccines are currently used in veterinary medicine, but have not achieved widespread acceptance for use in humans due to their low immunogenicity in early clinical studies. However, recent clinical data have re-established the value of DNA vaccines, particularly in priming high-level antigen-specific antibody responses. Several approaches have been investigated for improving DNA vaccine efficacy, including advancements in DNA vaccine vector design, the inclusion of genetically engineered cytokine adjuvants, and novel non-mechanical delivery methods. These strategies have shown promise, resulting in augmented adaptive immune responses in not only mice, but also in large animal models. Here, we review advancements in each of these areas that show promise for increasing the immunogenicity of DNA vaccines.

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Mutants of plant genes for developing cancer vaccines

Cited by 13 publications

References 33 publications

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

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

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

Advancements in DNA vaccine vectors, non-mechanical delivery methods, and molecular adjuvants to increase immunogenicity

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