Engineering the chloroplast targeted malarial vaccine antigens in Chlamydomonas starch granules.

<h4>Background</h4>Malaria, an Anopheles-borne parasitic disease, remains a major global health problem causing illness and death that disproportionately affects developing countries. Despite the incidence of malaria, which remains one of the most severe infections of human populations,...

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Autores principales:	David Dauvillée, Stéphane Delhaye, Sébastien Gruyer, Christian Slomianny, Samuel E Moretz, Christophe d'Hulst, Carole A Long, Steven G Ball, Stanislas Tomavo
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0af1bdb1b83b453897e5d4b2442684cf
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spelling	oai:doaj.org-article:0af1bdb1b83b453897e5d4b2442684cf2021-11-18T07:01:40ZEngineering the chloroplast targeted malarial vaccine antigens in Chlamydomonas starch granules.1932-620310.1371/journal.pone.0015424https://doaj.org/article/0af1bdb1b83b453897e5d4b2442684cf2010-12-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21179538/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Malaria, an Anopheles-borne parasitic disease, remains a major global health problem causing illness and death that disproportionately affects developing countries. Despite the incidence of malaria, which remains one of the most severe infections of human populations, there is no licensed vaccine against this life-threatening disease. In this context, we decided to explore the expression of Plasmodium vaccine antigens fused to the granule bound starch synthase (GBSS), the major protein associated to the starch matrix in all starch-accumulating plants and algae such as Chlamydomonas reinhardtii.<h4>Methods and findings</h4>We describe the development of genetically engineered starch granules containing plasmodial vaccine candidate antigens produced in the unicellular green algae Chlamydomonas reinhardtii. We show that the C-terminal domains of proteins from the rodent Plasmodium species, Plasmodium berghei Apical Major Antigen AMA1, or Major Surface Protein MSP1 fused to the algal granule bound starch synthase (GBSS) are efficiently expressed and bound to the polysaccharide matrix. Mice were either immunized intraperitoneally with the engineered starch particles and Freund adjuvant, or fed with the engineered particles co-delivered with the mucosal adjuvant, and challenged intraperitoneally with a lethal inoculum of P. Berghei. Both experimental strategies led to a significantly reduced parasitemia with an extension of life span including complete cure for intraperitoneal delivery as assessed by negative blood thin smears. In the case of the starch bound P. falciparum GBSS-MSP1 fusion protein, the immune sera or purified immunoglobulin G of mice immunized with the corresponding starch strongly inhibited in vitro the intra-erythrocytic asexual development of the most human deadly plasmodial species.<h4>Conclusion</h4>This novel system paves the way for the production of clinically relevant plasmodial antigens as algal starch-based particles designated herein as amylosomes, demonstrating that efficient production of edible vaccines can be genetically produced in Chlamydomonas.David DauvilléeStéphane DelhayeSébastien GruyerChristian SlomiannySamuel E MoretzChristophe d'HulstCarole A LongSteven G BallStanislas TomavoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 12, p e15424 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q David Dauvillée Stéphane Delhaye Sébastien Gruyer Christian Slomianny Samuel E Moretz Christophe d'Hulst Carole A Long Steven G Ball Stanislas Tomavo Engineering the chloroplast targeted malarial vaccine antigens in Chlamydomonas starch granules.
description	<h4>Background</h4>Malaria, an Anopheles-borne parasitic disease, remains a major global health problem causing illness and death that disproportionately affects developing countries. Despite the incidence of malaria, which remains one of the most severe infections of human populations, there is no licensed vaccine against this life-threatening disease. In this context, we decided to explore the expression of Plasmodium vaccine antigens fused to the granule bound starch synthase (GBSS), the major protein associated to the starch matrix in all starch-accumulating plants and algae such as Chlamydomonas reinhardtii.<h4>Methods and findings</h4>We describe the development of genetically engineered starch granules containing plasmodial vaccine candidate antigens produced in the unicellular green algae Chlamydomonas reinhardtii. We show that the C-terminal domains of proteins from the rodent Plasmodium species, Plasmodium berghei Apical Major Antigen AMA1, or Major Surface Protein MSP1 fused to the algal granule bound starch synthase (GBSS) are efficiently expressed and bound to the polysaccharide matrix. Mice were either immunized intraperitoneally with the engineered starch particles and Freund adjuvant, or fed with the engineered particles co-delivered with the mucosal adjuvant, and challenged intraperitoneally with a lethal inoculum of P. Berghei. Both experimental strategies led to a significantly reduced parasitemia with an extension of life span including complete cure for intraperitoneal delivery as assessed by negative blood thin smears. In the case of the starch bound P. falciparum GBSS-MSP1 fusion protein, the immune sera or purified immunoglobulin G of mice immunized with the corresponding starch strongly inhibited in vitro the intra-erythrocytic asexual development of the most human deadly plasmodial species.<h4>Conclusion</h4>This novel system paves the way for the production of clinically relevant plasmodial antigens as algal starch-based particles designated herein as amylosomes, demonstrating that efficient production of edible vaccines can be genetically produced in Chlamydomonas.
format	article
author	David Dauvillée Stéphane Delhaye Sébastien Gruyer Christian Slomianny Samuel E Moretz Christophe d'Hulst Carole A Long Steven G Ball Stanislas Tomavo
author_facet	David Dauvillée Stéphane Delhaye Sébastien Gruyer Christian Slomianny Samuel E Moretz Christophe d'Hulst Carole A Long Steven G Ball Stanislas Tomavo
author_sort	David Dauvillée
title	Engineering the chloroplast targeted malarial vaccine antigens in Chlamydomonas starch granules.
title_short	Engineering the chloroplast targeted malarial vaccine antigens in Chlamydomonas starch granules.
title_full	Engineering the chloroplast targeted malarial vaccine antigens in Chlamydomonas starch granules.
title_fullStr	Engineering the chloroplast targeted malarial vaccine antigens in Chlamydomonas starch granules.
title_full_unstemmed	Engineering the chloroplast targeted malarial vaccine antigens in Chlamydomonas starch granules.
title_sort	engineering the chloroplast targeted malarial vaccine antigens in chlamydomonas starch granules.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/0af1bdb1b83b453897e5d4b2442684cf
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Engineering the chloroplast targeted malarial vaccine antigens in Chlamydomonas starch granules.

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