Engineering DNA Vaccines that Include Plant Virus Coat Proteins

Savelyeva, Natalia; Zhu, Delin; Stevenson, Freda K.

doi:10.1080/02648725.2003.10648039

Cited by 11 publications

(12 citation statements)

References 9 publications

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“…A relatively new class of pathogen-derived sequences is represented by plant viral coat proteins (CPs). They can be used as carriers for several reasons: plant viruses are not human pathogens; they are able to self-assemble or to form highly immunogenic aggregates; and no evidence of preexisting immunity in humans has been described (Savelyeva et al, 2003).…”

Section: Figmentioning

confidence: 99%

“…CPs have been largely used as carrier proteins for a range of B cell epitopes from animal pathogens (Scholthof et al, 1996;Cañizares et al, 2005). Furthermore, by representing primary antigens in humans and having the ability to aggregate into structures able to increase the CD4 ϩ T cell immune response (Savelyeva et al, 2003), CPs act like dominant pathogen-derived antigens able to enhance immunogenicity of silent or poor determinants (Gerloni et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

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Antitumor Activity of DNA Vaccines Based on the Human Papillomavirus-16 E7 Protein Genetically Fused to a Plant Virus Coat Protein

Massa

Simeone²,

Müller³

et al. 2008

Human Gene Therapy

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DNA vaccination represents an attractive strategy for cancer immunotherapy combining vaccine stability, cost-effectiveness, and safety. However, a major problem of genetic vaccination is the limited potency, due to intrinsic lack of amplifying and spreading abilities in vivo and to the suboptimal intracellular processing/presentation of tumor antigens. We explored the therapeutic antitumor potency of DNA vaccines based on a mutated, nontransforming form of the E7 gene (E7GGG gene) of human papilloma virus 16 (HPV-16) fused, with or without a linker, to the potato virus X (PVX) coat protein sequence (PVX-CP). Transfection of mammalian cells demonstrated expression of the E7GGG protein, while the fusion proteins were detected only in the presence of proteasome inhibitors, suggesting increased instability and faster degradation via the proteasome. The DNA fusion vaccines, administered intramuscularly to C57BL/6 mice after challenging with a tumorigenic dose of E7-expressing TC-1 cells, inhibited the growth of tumors in vivo better than the E7GGG gene alone and induced both humoral and cell-mediated immune responses. Therefore, fusion of the HPV-16 E7GGG gene with a plant virus coat protein gene might be a valid strategy to induce antitumor immunity in a safe setting by a novel genetic vaccine targeting cervical carcinoma.

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Section: Figmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Antitumor Activity of DNA Vaccines Based on the Human Papillomavirus-16 E7 Protein Genetically Fused to a Plant Virus Coat Protein

Massa

Simeone²,

Müller³

et al. 2008

Human Gene Therapy

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“…Given the promising results obtained in vivo by the genetic E7GGGCP vaccine (Massa et al, 2008), a novel E6F47RCP DNA construct was generated by fusing the attenuated HPV16 E6F47R gene with the PVX-CP gene. This plant virus CP represents a dominant pathogenderived antigen and an innovative way to enhance the immunogenicity of the encoded product, as it increases the Th1 response (Massa et al, 2008;Savelyeva et al, 2001;Savelyeva et al, 2003) and reduces inappropriate immune responses and autoimmunity in therapeutic vaccination regimens.…”

Section: Discussionmentioning

confidence: 99%

“…On this basis, the new class of plant-virusderived sequences of the Potato virus X (PVX) coat protein (CP) can be a suitable carrier for antigen display. CP is recognized as a good immunogen for humans, and it can aggregate into structures that can increase CD4 + T-cell-mediated protection (Savelyeva et al, 2001;Savelyeva et al, 2003). PVX and PVX-CP have already been fused to different viral antigens for transient expression in plant and epitope-6 presentation systems (Cerovska et al, 2013;Franconi et al, 2002;Marusic et al, 2001) to develop more immunogenic vaccines.…”

mentioning

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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“…5,10 In a search of innovative immunostimulatory sequences with less clinical use constraints (i.e., possible auto-immune responses induced by proteins of human origin like calreticulin and Hsp70), our first strategy to enhance a HPV plasmid DNA vaccine potency was to fuse an attenuated HPV16 E7 (E7GGG) to the Potato Virus X coat protein, 11 a carrier that had been shown to increase CD4 + T-cell immune response ('linked T-cell help'), 12 and to enhance immunogenicity of silent or poor determinants. 13 In the present study a new strategy has been developed by using plant-derived carriers, the 'Ribosome inactivating proteins' (RIPs). RIPs are potent inhibitors of protein synthesis that accumulate in different organs of many plant species where they have a regulative and a defense role.…”

Section: E7gggmentioning

confidence: 99%