Expression optimization of a cell membrane-penetrating human papillomavirus type 16 therapeutic vaccine candidate in Nicotiana benthamiana
High-risk human papillomaviruses (hr-HPVs) cause cervical cancer, the fourth most common cancer in women worldwide. A HPV-16 candidate therapeutic vaccine, LALF32-51-E7, was developed by fusing a modified E7 protein to a bacterial cell-penetrating peptide (LALF): this elicited both tumour protection...
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| Veröffentlicht in: | PloS one 2017-08, Vol.12 (8), p.e0183177-e0183177 |
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| creator | Yanez, Romana J R Lamprecht, Renate Granadillo, Milaid Weber, Brandon Torrens, Isis Rybicki, Edward P Hitzeroth, Inga I |
| description | High-risk human papillomaviruses (hr-HPVs) cause cervical cancer, the fourth most common cancer in women worldwide. A HPV-16 candidate therapeutic vaccine, LALF32-51-E7, was developed by fusing a modified E7 protein to a bacterial cell-penetrating peptide (LALF): this elicited both tumour protection and regression in pre-clinical immunization studies. In the current study, we investigated the potential for producing LALF32-51-E7 in a plant expression system by evaluating the effect of subcellular localization and usage of different expression vectors and gene silencing suppressors. The highest expression levels of LALF32-51-E7 were obtained by using a self-replicating plant expression vector and chloroplast targeting, which increased its accumulation by 27-fold compared to cytoplasmic localization. The production and extraction of LALF32-51-E7 was scaled-up and purification optimized by affinity chromatography. If further developed, this platform could potentially allow for the production of a more affordable therapeutic vaccine for HPV-16. This would be extremely relevant in the context of developing countries, where cervical cancer and other HPV-related malignancies are most prevalent, and where the population have limited or no access to preventative vaccines due to their typical high costs. |
| doi_str_mv | 10.1371/journal.pone.0183177 |
| format | Article |
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A HPV-16 candidate therapeutic vaccine, LALF32-51-E7, was developed by fusing a modified E7 protein to a bacterial cell-penetrating peptide (LALF): this elicited both tumour protection and regression in pre-clinical immunization studies. In the current study, we investigated the potential for producing LALF32-51-E7 in a plant expression system by evaluating the effect of subcellular localization and usage of different expression vectors and gene silencing suppressors. The highest expression levels of LALF32-51-E7 were obtained by using a self-replicating plant expression vector and chloroplast targeting, which increased its accumulation by 27-fold compared to cytoplasmic localization. The production and extraction of LALF32-51-E7 was scaled-up and purification optimized by affinity chromatography. If further developed, this platform could potentially allow for the production of a more affordable therapeutic vaccine for HPV-16. This would be extremely relevant in the context of developing countries, where cervical cancer and other HPV-related malignancies are most prevalent, and where the population have limited or no access to preventative vaccines due to their typical high costs.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0183177</identifier><identifier>PMID: 28800364</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Affinity chromatography ; Agrobacterium - genetics ; Agrobacterium - metabolism ; Bacteria ; Biology ; Biology and Life Sciences ; Cancer ; Care and treatment ; Cell membranes ; Cervical cancer ; Cervix ; Chloroplasts ; Chloroplasts - genetics ; Chloroplasts - metabolism ; Chromatography ; Developing countries ; Dosage and administration ; E7 protein ; Escherichia coli - genetics ; Escherichia coli - metabolism ; Expression vectors ; Female ; Gene Expression ; Gene silencing ; Gene Silencing - immunology ; Genetic engineering ; Genetic Vectors - chemistry ; Genetic Vectors - metabolism ; Health risks ; Human papillomavirus ; Human papillomavirus 16 - chemistry ; Human papillomavirus 16 - immunology ; Humans ; Immunization ; Infections ; Laboratories ; LDCs ; Leaves ; Localization ; Medicine and Health Sciences ; Nicotiana - genetics ; Nicotiana - metabolism ; Observatories ; Optimization ; Papillomaviridae ; Papillomavirus E7 Proteins - biosynthesis ; Papillomavirus E7 Proteins - genetics ; Papillomavirus E7 Proteins - immunology ; Papillomavirus infections ; Papillomavirus Infections - immunology ; Papillomavirus Infections - prevention & control ; Papillomavirus Infections - virology ; Papillomavirus Vaccines - biosynthesis ; Papillomavirus Vaccines - genetics ; Papillomavirus Vaccines - immunology ; Peptides ; Peptides - genetics ; Peptides - immunology ; Peptides - metabolism ; Proteins ; Recombinant Proteins - biosynthesis ; Recombinant Proteins - genetics ; Recombinant Proteins - immunology ; Replication ; Research and Analysis Methods ; Risk factors ; Studies ; Suppressors ; Tobacco (Plant) ; Tumors ; Uterine Cervical Neoplasms - immunology ; Uterine Cervical Neoplasms - prevention & control ; Uterine Cervical Neoplasms - virology ; Vaccines</subject><ispartof>PloS one, 2017-08, Vol.12 (8), p.e0183177-e0183177</ispartof><rights>COPYRIGHT 2017 Public Library of Science</rights><rights>2017 Yanez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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A HPV-16 candidate therapeutic vaccine, LALF32-51-E7, was developed by fusing a modified E7 protein to a bacterial cell-penetrating peptide (LALF): this elicited both tumour protection and regression in pre-clinical immunization studies. In the current study, we investigated the potential for producing LALF32-51-E7 in a plant expression system by evaluating the effect of subcellular localization and usage of different expression vectors and gene silencing suppressors. The highest expression levels of LALF32-51-E7 were obtained by using a self-replicating plant expression vector and chloroplast targeting, which increased its accumulation by 27-fold compared to cytoplasmic localization. The production and extraction of LALF32-51-E7 was scaled-up and purification optimized by affinity chromatography. If further developed, this platform could potentially allow for the production of a more affordable therapeutic vaccine for HPV-16. 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yanez, Romana J R</au><au>Lamprecht, Renate</au><au>Granadillo, Milaid</au><au>Weber, Brandon</au><au>Torrens, Isis</au><au>Rybicki, Edward P</au><au>Hitzeroth, Inga I</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Expression optimization of a cell membrane-penetrating human papillomavirus type 16 therapeutic vaccine candidate in Nicotiana benthamiana</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2017-08-11</date><risdate>2017</risdate><volume>12</volume><issue>8</issue><spage>e0183177</spage><epage>e0183177</epage><pages>e0183177-e0183177</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>High-risk human papillomaviruses (hr-HPVs) cause cervical cancer, the fourth most common cancer in women worldwide. A HPV-16 candidate therapeutic vaccine, LALF32-51-E7, was developed by fusing a modified E7 protein to a bacterial cell-penetrating peptide (LALF): this elicited both tumour protection and regression in pre-clinical immunization studies. In the current study, we investigated the potential for producing LALF32-51-E7 in a plant expression system by evaluating the effect of subcellular localization and usage of different expression vectors and gene silencing suppressors. The highest expression levels of LALF32-51-E7 were obtained by using a self-replicating plant expression vector and chloroplast targeting, which increased its accumulation by 27-fold compared to cytoplasmic localization. The production and extraction of LALF32-51-E7 was scaled-up and purification optimized by affinity chromatography. If further developed, this platform could potentially allow for the production of a more affordable therapeutic vaccine for HPV-16. This would be extremely relevant in the context of developing countries, where cervical cancer and other HPV-related malignancies are most prevalent, and where the population have limited or no access to preventative vaccines due to their typical high costs.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>28800364</pmid><doi>10.1371/journal.pone.0183177</doi><tpages>e0183177</tpages><orcidid>https://orcid.org/0000-0002-8515-9525</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2017-08, Vol.12 (8), p.e0183177-e0183177 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1927973515 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Affinity chromatography Agrobacterium - genetics Agrobacterium - metabolism Bacteria Biology Biology and Life Sciences Cancer Care and treatment Cell membranes Cervical cancer Cervix Chloroplasts Chloroplasts - genetics Chloroplasts - metabolism Chromatography Developing countries Dosage and administration E7 protein Escherichia coli - genetics Escherichia coli - metabolism Expression vectors Female Gene Expression Gene silencing Gene Silencing - immunology Genetic engineering Genetic Vectors - chemistry Genetic Vectors - metabolism Health risks Human papillomavirus Human papillomavirus 16 - chemistry Human papillomavirus 16 - immunology Humans Immunization Infections Laboratories LDCs Leaves Localization Medicine and Health Sciences Nicotiana - genetics Nicotiana - metabolism Observatories Optimization Papillomaviridae Papillomavirus E7 Proteins - biosynthesis Papillomavirus E7 Proteins - genetics Papillomavirus E7 Proteins - immunology Papillomavirus infections Papillomavirus Infections - immunology Papillomavirus Infections - prevention & control Papillomavirus Infections - virology Papillomavirus Vaccines - biosynthesis Papillomavirus Vaccines - genetics Papillomavirus Vaccines - immunology Peptides Peptides - genetics Peptides - immunology Peptides - metabolism Proteins Recombinant Proteins - biosynthesis Recombinant Proteins - genetics Recombinant Proteins - immunology Replication Research and Analysis Methods Risk factors Studies Suppressors Tobacco (Plant) Tumors Uterine Cervical Neoplasms - immunology Uterine Cervical Neoplasms - prevention & control Uterine Cervical Neoplasms - virology Vaccines |
| title | Expression optimization of a cell membrane-penetrating human papillomavirus type 16 therapeutic vaccine candidate in Nicotiana benthamiana |
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