Human papillomavirus (HPV) type 16 E7 protein bodies cause tumour regression in mice

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dc.contributor.authorWhitehead, Mark
dc.contributor.authorÖhlschläger, Peter
dc.contributor.authorAlmajhdi, Fahad N
dc.contributor.authorAlloza, Leonor
dc.contributor.authorMarzábal, Pablo
dc.contributor.authorMeyers, Ann E
dc.contributor.authorHitzeroth, Inga I
dc.contributor.authorRybicki, Edward P
dc.date.accessioned2015-06-30T12:11:51Z
dc.date.available2015-06-30T12:11:51Z
dc.date.issued2014-05-24
dc.date.updated2015-01-15T17:57:00Z
dc.description.abstractAbstract Background Human papillomaviruses (HPV) are the causative agents of cervical cancer in women, which results in over 250 000 deaths per year. Presently there are two prophylactic vaccines on the market, protecting against the two most common high-risk HPV types 16 and 18. These vaccines remain very expensive and are not generally affordable in developing countries where they are needed most. Additionally, there remains a need to treat women that are already infected with HPV, and who have high-grade lesions or cervical cancer. Methods In this paper, we characterize the immunogenicity of a therapeutic vaccine that targets the E7 protein of the most prevalent high-risk HPV - type 16 – the gene which has previously been shown to be effective in DNA vaccine trials in mice. The synthetic shuffled HPV-16 E7 (16E7SH) has lost its transforming properties but retains all naturally-occurring CTL epitopes. This was genetically fused to Zera®, a self-assembly domain of the maize γ-zein able to induce the accumulation of recombinant proteins into protein bodies (PBs), within the endoplasmic reticulum in a number of expression systems. Results High-level expression of the HPV 16E7SH protein fused to Zera® in plants was achieved, and the protein bodies could be easily and cost-effectively purified. Immune responses comparable to the 16E7SH DNA vaccine were demonstrated in the murine model, with the protein vaccine successfully inducing a specific humoral as well as cell mediated immune response, and mediating tumour regression. Conclusions The fusion of 16E7SH to the Zera® peptide was found to enhance the immune responses, presumably by means of a more efficient antigen presentation via the protein bodies. Interestingly, simply mixing the free PBs and 16E7SH also enhanced immune responses, indicating an adjuvant activity for the Zera® PBs.
dc.identifier.apacitationWhitehead, M., Öhlschläger, P., Almajhdi, F. N., Alloza, L., Marzábal, P., Meyers, A. E., ... Rybicki, E. P. (2014). Human papillomavirus (HPV) type 16 E7 protein bodies cause tumour regression in mice. <i>BMC Cancer</i>, http://hdl.handle.net/11427/13193en_ZA
dc.identifier.chicagocitationWhitehead, Mark, Peter Öhlschläger, Fahad N Almajhdi, Leonor Alloza, Pablo Marzábal, Ann E Meyers, Inga I Hitzeroth, and Edward P Rybicki "Human papillomavirus (HPV) type 16 E7 protein bodies cause tumour regression in mice." <i>BMC Cancer</i> (2014) http://hdl.handle.net/11427/13193en_ZA
dc.identifier.citationWhitehead, M., Öhlschläger, P., Almajhdi, F. N., Alloza, L., Marzábal, P., Meyers, A. E., ... & Rybicki, E. P. (2014). Human papillomavirus (HPV) type 16 E7 protein bodies cause tumour regression in mice. BMC cancer, 14(1), 367.
dc.identifier.ris TY - Journal Article AU - Whitehead, Mark AU - Öhlschläger, Peter AU - Almajhdi, Fahad N AU - Alloza, Leonor AU - Marzábal, Pablo AU - Meyers, Ann E AU - Hitzeroth, Inga I AU - Rybicki, Edward P AB - Abstract Background Human papillomaviruses (HPV) are the causative agents of cervical cancer in women, which results in over 250 000 deaths per year. Presently there are two prophylactic vaccines on the market, protecting against the two most common high-risk HPV types 16 and 18. These vaccines remain very expensive and are not generally affordable in developing countries where they are needed most. Additionally, there remains a need to treat women that are already infected with HPV, and who have high-grade lesions or cervical cancer. Methods In this paper, we characterize the immunogenicity of a therapeutic vaccine that targets the E7 protein of the most prevalent high-risk HPV - type 16 – the gene which has previously been shown to be effective in DNA vaccine trials in mice. The synthetic shuffled HPV-16 E7 (16E7SH) has lost its transforming properties but retains all naturally-occurring CTL epitopes. This was genetically fused to Zera®, a self-assembly domain of the maize γ-zein able to induce the accumulation of recombinant proteins into protein bodies (PBs), within the endoplasmic reticulum in a number of expression systems. Results High-level expression of the HPV 16E7SH protein fused to Zera® in plants was achieved, and the protein bodies could be easily and cost-effectively purified. Immune responses comparable to the 16E7SH DNA vaccine were demonstrated in the murine model, with the protein vaccine successfully inducing a specific humoral as well as cell mediated immune response, and mediating tumour regression. Conclusions The fusion of 16E7SH to the Zera® peptide was found to enhance the immune responses, presumably by means of a more efficient antigen presentation via the protein bodies. Interestingly, simply mixing the free PBs and 16E7SH also enhanced immune responses, indicating an adjuvant activity for the Zera® PBs. DA - 2014-05-24 DB - OpenUCT DO - 10.1186/1471-2407-14-367 DP - University of Cape Town J1 - BMC Cancer LK - https://open.uct.ac.za PB - University of Cape Town PY - 2014 T1 - Human papillomavirus (HPV) type 16 E7 protein bodies cause tumour regression in mice TI - Human papillomavirus (HPV) type 16 E7 protein bodies cause tumour regression in mice UR - http://hdl.handle.net/11427/13193 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/13193
dc.identifier.urihttp://dx.doi.org/10.1186/1471-2407-14-367
dc.identifier.vancouvercitationWhitehead M, Öhlschläger P, Almajhdi FN, Alloza L, Marzábal P, Meyers AE, et al. Human papillomavirus (HPV) type 16 E7 protein bodies cause tumour regression in mice. BMC Cancer. 2014; http://hdl.handle.net/11427/13193.en_ZA
dc.language.rfc3066en
dc.publisher.departmentDepartment of Molecular and Cell Biologyen_ZA
dc.publisher.facultyFaculty of Scienceen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an Open Access article distributed under the terms of the Creative Commons Attribution License*
dc.rights.holderWhitehead et al.; licensee BioMed Central Ltd.
dc.rights.urihttp://creativecommons.org/licenses/by/2.0*
dc.sourceBMC Canceren_ZA
dc.source.urihttp://www.biomedcentral.com/bmccancer/
dc.subject.otherCervical canceren_ZA
dc.subject.otherDNA vaccineen_ZA
dc.subject.otherHPV-16en_ZA
dc.subject.otherE7en_ZA
dc.subject.otherZera® proteinen_ZA
dc.subject.otherProtein bodyen_ZA
dc.subject.otherPlant-produceden_ZA
dc.titleHuman papillomavirus (HPV) type 16 E7 protein bodies cause tumour regression in mice
dc.typeJournal Articleen_ZA
uct.type.filetype
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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