Utilizing nanobody technology to target non-immunodominant domains of VAR2CSA.

Placental malaria is a major health problem for both pregnant women and their fetuses in malaria endemic regions. It is triggered by the accumulation of Plasmodium falciparum-infected erythrocytes (IE) in the intervillous spaces of the placenta and is associated with foetal growth restriction and ma...

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Autores principales:	Sisse B Ditlev, Raluca Florea, Morten A Nielsen, Thor G Theander, Stefan Magez, Philippe Boeuf, Ali Salanti
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9796993b115b40e59cdd32de388a16ae
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spelling	oai:doaj.org-article:9796993b115b40e59cdd32de388a16ae2021-11-18T08:37:07ZUtilizing nanobody technology to target non-immunodominant domains of VAR2CSA.1932-620310.1371/journal.pone.0084981https://doaj.org/article/9796993b115b40e59cdd32de388a16ae2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24465459/?tool=EBIhttps://doaj.org/toc/1932-6203Placental malaria is a major health problem for both pregnant women and their fetuses in malaria endemic regions. It is triggered by the accumulation of Plasmodium falciparum-infected erythrocytes (IE) in the intervillous spaces of the placenta and is associated with foetal growth restriction and maternal anemia. IE accumulation is supported by the binding of the parasite-expressed protein VAR2CSA to placental chondroitin sulfate A (CSA). Defining specific CSA-binding epitopes of VAR2CSA, against which to target the immune response, is essential for the development of a vaccine aimed at blocking IE adhesion. However, the development of a VAR2CSA adhesion-blocking vaccine remains challenging due to (i) the large size of VAR2CSA and (ii) the extensive immune selection for polymorphisms and thereby non-neutralizing B-cell epitopes. Camelid heavy-chain-only antibodies (HcAbs) are known to target epitopes that are less immunogenic to classical IgG and, due to their small size and protruding antigen-binding loop, able to reach and recognize cryptic, conformational epitopes which are inaccessible to conventional antibodies. The variable heavy chain (VHH) domain is the antigen-binding site of camelid HcAbs, the so called Nanobody, which represents the smallest known (15 kDa) intact, native antigen-binding fragment. In this study, we have used the Nanobody technology, an approach new to malaria research, to generate small and functional antibody fragments recognizing unique epitopes broadly distributed on VAR2CSA.Sisse B DitlevRaluca FloreaMorten A NielsenThor G TheanderStefan MagezPhilippe BoeufAli SalantiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 1, p e84981 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sisse B Ditlev Raluca Florea Morten A Nielsen Thor G Theander Stefan Magez Philippe Boeuf Ali Salanti Utilizing nanobody technology to target non-immunodominant domains of VAR2CSA.
description	Placental malaria is a major health problem for both pregnant women and their fetuses in malaria endemic regions. It is triggered by the accumulation of Plasmodium falciparum-infected erythrocytes (IE) in the intervillous spaces of the placenta and is associated with foetal growth restriction and maternal anemia. IE accumulation is supported by the binding of the parasite-expressed protein VAR2CSA to placental chondroitin sulfate A (CSA). Defining specific CSA-binding epitopes of VAR2CSA, against which to target the immune response, is essential for the development of a vaccine aimed at blocking IE adhesion. However, the development of a VAR2CSA adhesion-blocking vaccine remains challenging due to (i) the large size of VAR2CSA and (ii) the extensive immune selection for polymorphisms and thereby non-neutralizing B-cell epitopes. Camelid heavy-chain-only antibodies (HcAbs) are known to target epitopes that are less immunogenic to classical IgG and, due to their small size and protruding antigen-binding loop, able to reach and recognize cryptic, conformational epitopes which are inaccessible to conventional antibodies. The variable heavy chain (VHH) domain is the antigen-binding site of camelid HcAbs, the so called Nanobody, which represents the smallest known (15 kDa) intact, native antigen-binding fragment. In this study, we have used the Nanobody technology, an approach new to malaria research, to generate small and functional antibody fragments recognizing unique epitopes broadly distributed on VAR2CSA.
format	article
author	Sisse B Ditlev Raluca Florea Morten A Nielsen Thor G Theander Stefan Magez Philippe Boeuf Ali Salanti
author_facet	Sisse B Ditlev Raluca Florea Morten A Nielsen Thor G Theander Stefan Magez Philippe Boeuf Ali Salanti
author_sort	Sisse B Ditlev
title	Utilizing nanobody technology to target non-immunodominant domains of VAR2CSA.
title_short	Utilizing nanobody technology to target non-immunodominant domains of VAR2CSA.
title_full	Utilizing nanobody technology to target non-immunodominant domains of VAR2CSA.
title_fullStr	Utilizing nanobody technology to target non-immunodominant domains of VAR2CSA.
title_full_unstemmed	Utilizing nanobody technology to target non-immunodominant domains of VAR2CSA.
title_sort	utilizing nanobody technology to target non-immunodominant domains of var2csa.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/9796993b115b40e59cdd32de388a16ae
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Utilizing nanobody technology to target non-immunodominant domains of VAR2CSA.

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