Strain-transcendent immune response to recombinant Var2CSA DBL5-ε domain block P. falciparum adhesion to placenta-derived BeWo cells under flow conditions.

<h4>Background</h4>Pregnancy-associated malaria (PAM) is a serious consequence of the adhesion to the placental receptor chondroitin sulfate A (CSA) of Plasmodium falciparum-infected erythrocytes (PE) expressing the large cysteine-rich multi-domain protein var2CSA. Women become resistant...

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Autores principales:	Pablo Fernandez, Stéphane Petres, Salaheddine Mécheri, Jürg Gysin, Artur Scherf
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e48f41ca6fbf411dad79c6a738246f73
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spelling	oai:doaj.org-article:e48f41ca6fbf411dad79c6a738246f732021-11-18T06:35:28ZStrain-transcendent immune response to recombinant Var2CSA DBL5-ε domain block P. falciparum adhesion to placenta-derived BeWo cells under flow conditions.1932-620310.1371/journal.pone.0012558https://doaj.org/article/e48f41ca6fbf411dad79c6a738246f732010-09-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20838433/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Pregnancy-associated malaria (PAM) is a serious consequence of the adhesion to the placental receptor chondroitin sulfate A (CSA) of Plasmodium falciparum-infected erythrocytes (PE) expressing the large cysteine-rich multi-domain protein var2CSA. Women become resistant to PAM, and develop strain-transcending immunity against CSA-binding parasites. The identification of var2CSA regions that could elicit broadly neutralizing and adhesion-blocking antibodies is a key step for the design of prophylactic vaccine strategies.<h4>Methodology</h4>Escherichia coli expressed var2CSA DBL domains were refolded and purified prior to immunization of mice and a goat. Protein-G-purified antibodies were tested for their ability to block FCR3(CSA)-infected erythrocytes binding to placental (BeWo) and monkey brain endothelial (ScC2) cell lines using a flow cytoadhesion inhibition assay mimicking closely the physiological conditions present in the placenta at shear stress of 0.05 Pa. DBL5-ε, DBL6-ε and DBL5-6-ε induced cross-reactive antibodies using Alum and Freund as adjuvants, which blocked cytoadhesion at values ranging between 40 to 96% at 0.5 mg IgG per ml. Importantly, antibodies raised against recombinant DBL5-ε from 3 distinct parasites genotypes (HB3, Dd2 and 7G8) showed strain-transcending inhibition ranging from 38 to 64% for the heterologuous FCR3(CSA).<h4>Conclusions</h4>Using single and double DBL domains from var2CSA and Alum as adjuvant, we identified recombinant subunits inducing an immune response in experimental animals which is able to block efficiently parasite adhesion in a flow cytoadhesion assay that mimics closely the erythrocyte flow in the placenta. These subunits show promising features for inclusion into a vaccine aiming to protect against PAM.Pablo FernandezStéphane PetresSalaheddine MécheriJürg GysinArtur ScherfPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 9, p e12558 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Pablo Fernandez Stéphane Petres Salaheddine Mécheri Jürg Gysin Artur Scherf Strain-transcendent immune response to recombinant Var2CSA DBL5-ε domain block P. falciparum adhesion to placenta-derived BeWo cells under flow conditions.
description	<h4>Background</h4>Pregnancy-associated malaria (PAM) is a serious consequence of the adhesion to the placental receptor chondroitin sulfate A (CSA) of Plasmodium falciparum-infected erythrocytes (PE) expressing the large cysteine-rich multi-domain protein var2CSA. Women become resistant to PAM, and develop strain-transcending immunity against CSA-binding parasites. The identification of var2CSA regions that could elicit broadly neutralizing and adhesion-blocking antibodies is a key step for the design of prophylactic vaccine strategies.<h4>Methodology</h4>Escherichia coli expressed var2CSA DBL domains were refolded and purified prior to immunization of mice and a goat. Protein-G-purified antibodies were tested for their ability to block FCR3(CSA)-infected erythrocytes binding to placental (BeWo) and monkey brain endothelial (ScC2) cell lines using a flow cytoadhesion inhibition assay mimicking closely the physiological conditions present in the placenta at shear stress of 0.05 Pa. DBL5-ε, DBL6-ε and DBL5-6-ε induced cross-reactive antibodies using Alum and Freund as adjuvants, which blocked cytoadhesion at values ranging between 40 to 96% at 0.5 mg IgG per ml. Importantly, antibodies raised against recombinant DBL5-ε from 3 distinct parasites genotypes (HB3, Dd2 and 7G8) showed strain-transcending inhibition ranging from 38 to 64% for the heterologuous FCR3(CSA).<h4>Conclusions</h4>Using single and double DBL domains from var2CSA and Alum as adjuvant, we identified recombinant subunits inducing an immune response in experimental animals which is able to block efficiently parasite adhesion in a flow cytoadhesion assay that mimics closely the erythrocyte flow in the placenta. These subunits show promising features for inclusion into a vaccine aiming to protect against PAM.
format	article
author	Pablo Fernandez Stéphane Petres Salaheddine Mécheri Jürg Gysin Artur Scherf
author_facet	Pablo Fernandez Stéphane Petres Salaheddine Mécheri Jürg Gysin Artur Scherf
author_sort	Pablo Fernandez
title	Strain-transcendent immune response to recombinant Var2CSA DBL5-ε domain block P. falciparum adhesion to placenta-derived BeWo cells under flow conditions.
title_short	Strain-transcendent immune response to recombinant Var2CSA DBL5-ε domain block P. falciparum adhesion to placenta-derived BeWo cells under flow conditions.
title_full	Strain-transcendent immune response to recombinant Var2CSA DBL5-ε domain block P. falciparum adhesion to placenta-derived BeWo cells under flow conditions.
title_fullStr	Strain-transcendent immune response to recombinant Var2CSA DBL5-ε domain block P. falciparum adhesion to placenta-derived BeWo cells under flow conditions.
title_full_unstemmed	Strain-transcendent immune response to recombinant Var2CSA DBL5-ε domain block P. falciparum adhesion to placenta-derived BeWo cells under flow conditions.
title_sort	strain-transcendent immune response to recombinant var2csa dbl5-ε domain block p. falciparum adhesion to placenta-derived bewo cells under flow conditions.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/e48f41ca6fbf411dad79c6a738246f73
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Strain-transcendent immune response to recombinant Var2CSA DBL5-ε domain block P. falciparum adhesion to placenta-derived BeWo cells under flow conditions.

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