A Chlamydomonas-derived Human Papillomavirus 16 E7 vaccine induces specific tumor protection.

<h4>Background</h4>The E7 protein of the Human Papillomavirus (HPV) type 16, being involved in malignant cellular transformation, represents a key antigen for developing therapeutic vaccines against HPV-related lesions and cancers. Recombinant production of this vaccine antigen in an act...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Olivia C Demurtas, Silvia Massa, Paola Ferrante, Aldo Venuti, Rosella Franconi, Giovanni Giuliano
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0963fa34853949e3bb62bab97b1d3536
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:0963fa34853949e3bb62bab97b1d3536
record_format	dspace
spelling	oai:doaj.org-article:0963fa34853949e3bb62bab97b1d35362021-11-18T07:48:28ZA Chlamydomonas-derived Human Papillomavirus 16 E7 vaccine induces specific tumor protection.1932-620310.1371/journal.pone.0061473https://doaj.org/article/0963fa34853949e3bb62bab97b1d35362013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23626690/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>The E7 protein of the Human Papillomavirus (HPV) type 16, being involved in malignant cellular transformation, represents a key antigen for developing therapeutic vaccines against HPV-related lesions and cancers. Recombinant production of this vaccine antigen in an active form and in compliance with good manufacturing practices (GMP) plays a crucial role for developing effective vaccines. E7-based therapeutic vaccines produced in plants have been shown to be active in tumor regression and protection in pre-clinical models. However, some drawbacks of in whole-plant vaccine production encouraged us to explore the production of the E7-based therapeutic vaccine in Chlamydomonas reinhardtii, an organism easy to grow and transform and fully amenable to GMP guidelines.<h4>Methodology/principal findings</h4>An expression cassette encoding E7GGG, a mutated, attenuated form of the E7 oncoprotein, alone or as a fusion with affinity tags (His6 or FLAG), under the control of the C. reinhardtii chloroplast psbD 5' UTR and the psbA 3' UTR, was introduced into the C. reinhardtii chloroplast genome by homologous recombination. The protein was mostly soluble and reached 0.12% of total soluble proteins. Affinity purification was optimized and performed for both tagged forms. Induction of specific anti-E7 IgGs and E7-specific T-cell proliferation were detected in C57BL/6 mice vaccinated with total Chlamydomonas extract and with affinity-purified protein. High levels of tumor protection were achieved after challenge with a tumor cell line expressing the E7 protein.<h4>Conclusions</h4>The C. reinhardtii chloroplast is a suitable expression system for the production of the E7GGG protein, in a soluble, immunogenic form. The production in contained and sterile conditions highlights the potential of microalgae as alternative platforms for the production of vaccines for human uses.Olivia C DemurtasSilvia MassaPaola FerranteAldo VenutiRosella FranconiGiovanni GiulianoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 4, p e61473 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Olivia C Demurtas Silvia Massa Paola Ferrante Aldo Venuti Rosella Franconi Giovanni Giuliano A Chlamydomonas-derived Human Papillomavirus 16 E7 vaccine induces specific tumor protection.
description	<h4>Background</h4>The E7 protein of the Human Papillomavirus (HPV) type 16, being involved in malignant cellular transformation, represents a key antigen for developing therapeutic vaccines against HPV-related lesions and cancers. Recombinant production of this vaccine antigen in an active form and in compliance with good manufacturing practices (GMP) plays a crucial role for developing effective vaccines. E7-based therapeutic vaccines produced in plants have been shown to be active in tumor regression and protection in pre-clinical models. However, some drawbacks of in whole-plant vaccine production encouraged us to explore the production of the E7-based therapeutic vaccine in Chlamydomonas reinhardtii, an organism easy to grow and transform and fully amenable to GMP guidelines.<h4>Methodology/principal findings</h4>An expression cassette encoding E7GGG, a mutated, attenuated form of the E7 oncoprotein, alone or as a fusion with affinity tags (His6 or FLAG), under the control of the C. reinhardtii chloroplast psbD 5' UTR and the psbA 3' UTR, was introduced into the C. reinhardtii chloroplast genome by homologous recombination. The protein was mostly soluble and reached 0.12% of total soluble proteins. Affinity purification was optimized and performed for both tagged forms. Induction of specific anti-E7 IgGs and E7-specific T-cell proliferation were detected in C57BL/6 mice vaccinated with total Chlamydomonas extract and with affinity-purified protein. High levels of tumor protection were achieved after challenge with a tumor cell line expressing the E7 protein.<h4>Conclusions</h4>The C. reinhardtii chloroplast is a suitable expression system for the production of the E7GGG protein, in a soluble, immunogenic form. The production in contained and sterile conditions highlights the potential of microalgae as alternative platforms for the production of vaccines for human uses.
format	article
author	Olivia C Demurtas Silvia Massa Paola Ferrante Aldo Venuti Rosella Franconi Giovanni Giuliano
author_facet	Olivia C Demurtas Silvia Massa Paola Ferrante Aldo Venuti Rosella Franconi Giovanni Giuliano
author_sort	Olivia C Demurtas
title	A Chlamydomonas-derived Human Papillomavirus 16 E7 vaccine induces specific tumor protection.
title_short	A Chlamydomonas-derived Human Papillomavirus 16 E7 vaccine induces specific tumor protection.
title_full	A Chlamydomonas-derived Human Papillomavirus 16 E7 vaccine induces specific tumor protection.
title_fullStr	A Chlamydomonas-derived Human Papillomavirus 16 E7 vaccine induces specific tumor protection.
title_full_unstemmed	A Chlamydomonas-derived Human Papillomavirus 16 E7 vaccine induces specific tumor protection.
title_sort	chlamydomonas-derived human papillomavirus 16 e7 vaccine induces specific tumor protection.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/0963fa34853949e3bb62bab97b1d3536
work_keys_str_mv	AT oliviacdemurtas achlamydomonasderivedhumanpapillomavirus16e7vaccineinducesspecifictumorprotection AT silviamassa achlamydomonasderivedhumanpapillomavirus16e7vaccineinducesspecifictumorprotection AT paolaferrante achlamydomonasderivedhumanpapillomavirus16e7vaccineinducesspecifictumorprotection AT aldovenuti achlamydomonasderivedhumanpapillomavirus16e7vaccineinducesspecifictumorprotection AT rosellafranconi achlamydomonasderivedhumanpapillomavirus16e7vaccineinducesspecifictumorprotection AT giovannigiuliano achlamydomonasderivedhumanpapillomavirus16e7vaccineinducesspecifictumorprotection AT oliviacdemurtas chlamydomonasderivedhumanpapillomavirus16e7vaccineinducesspecifictumorprotection AT silviamassa chlamydomonasderivedhumanpapillomavirus16e7vaccineinducesspecifictumorprotection AT paolaferrante chlamydomonasderivedhumanpapillomavirus16e7vaccineinducesspecifictumorprotection AT aldovenuti chlamydomonasderivedhumanpapillomavirus16e7vaccineinducesspecifictumorprotection AT rosellafranconi chlamydomonasderivedhumanpapillomavirus16e7vaccineinducesspecifictumorprotection AT giovannigiuliano chlamydomonasderivedhumanpapillomavirus16e7vaccineinducesspecifictumorprotection
_version_	1718422892477153280

A Chlamydomonas-derived Human Papillomavirus 16 E7 vaccine induces specific tumor protection.

Ejemplares similares