Structural insights into global mutations in the ligand-binding domain of VAR2CSA and its implications on placental malaria vaccine

Placental malaria is a public health burden particularly in Africa as it causes severe symptoms and results in stillbirths or maternal deaths. Plasmodium falciparum protein VAR2CSA drives placental malaria (PM) in pregnant women by adhering to chondroitin sulfate A (CSA) on the placenta. VAR2CSA is...

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Autores principales:	Jasmita Gill, Soumyananda Chakraborti, Praveen Bharti, Amit Sharma
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Placental malaria VAR2CSA Placental malaria vaccine Field isolates, Structural mapping Infectious and parasitic diseases RC109-216
Acceso en línea:	https://doaj.org/article/4d93b7dffb8048b6804bbe02d5ef6b4c
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spelling	oai:doaj.org-article:4d93b7dffb8048b6804bbe02d5ef6b4c2021-11-30T04:14:01ZStructural insights into global mutations in the ligand-binding domain of VAR2CSA and its implications on placental malaria vaccine1201-971210.1016/j.ijid.2021.08.054https://doaj.org/article/4d93b7dffb8048b6804bbe02d5ef6b4c2021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S1201971221006871https://doaj.org/toc/1201-9712Placental malaria is a public health burden particularly in Africa as it causes severe symptoms and results in stillbirths or maternal deaths. Plasmodium falciparum protein VAR2CSA drives placental malaria (PM) in pregnant women by adhering to chondroitin sulfate A (CSA) on the placenta. VAR2CSA is a primary vaccine candidate for PM with two vaccines based on it already under clinical trials. The first cryo-EM three-dimensional structure of Pf CSA-VAR2CSA complex revealed crucial interacting residues considered to be highly conserved across P. falciparum strains. In the current study, we have conducted a global sequence analysis of 1,114 VAR2CSA field isolate sequences from more than nine countries across three continents revealing numerous mutations in CSA-binding residues. Further, structural mapping has revealed significant polymorphisms on the ligand binding surfaces. The variants from this limited set of 1,114 sequences highlight the concerns that are vital in current considerations for development of vaccines based on VAR2CSA for placental malaria.Jasmita GillSoumyananda ChakrabortiPraveen BhartiAmit SharmaElsevierarticlePlacental malariaVAR2CSAPlacental malaria vaccineField isolates, Structural mappingInfectious and parasitic diseasesRC109-216ENInternational Journal of Infectious Diseases, Vol 112, Iss , Pp 35-39 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Placental malaria VAR2CSA Placental malaria vaccine Field isolates, Structural mapping Infectious and parasitic diseases RC109-216
spellingShingle	Placental malaria VAR2CSA Placental malaria vaccine Field isolates, Structural mapping Infectious and parasitic diseases RC109-216 Jasmita Gill Soumyananda Chakraborti Praveen Bharti Amit Sharma Structural insights into global mutations in the ligand-binding domain of VAR2CSA and its implications on placental malaria vaccine
description	Placental malaria is a public health burden particularly in Africa as it causes severe symptoms and results in stillbirths or maternal deaths. Plasmodium falciparum protein VAR2CSA drives placental malaria (PM) in pregnant women by adhering to chondroitin sulfate A (CSA) on the placenta. VAR2CSA is a primary vaccine candidate for PM with two vaccines based on it already under clinical trials. The first cryo-EM three-dimensional structure of Pf CSA-VAR2CSA complex revealed crucial interacting residues considered to be highly conserved across P. falciparum strains. In the current study, we have conducted a global sequence analysis of 1,114 VAR2CSA field isolate sequences from more than nine countries across three continents revealing numerous mutations in CSA-binding residues. Further, structural mapping has revealed significant polymorphisms on the ligand binding surfaces. The variants from this limited set of 1,114 sequences highlight the concerns that are vital in current considerations for development of vaccines based on VAR2CSA for placental malaria.
format	article
author	Jasmita Gill Soumyananda Chakraborti Praveen Bharti Amit Sharma
author_facet	Jasmita Gill Soumyananda Chakraborti Praveen Bharti Amit Sharma
author_sort	Jasmita Gill
title	Structural insights into global mutations in the ligand-binding domain of VAR2CSA and its implications on placental malaria vaccine
title_short	Structural insights into global mutations in the ligand-binding domain of VAR2CSA and its implications on placental malaria vaccine
title_full	Structural insights into global mutations in the ligand-binding domain of VAR2CSA and its implications on placental malaria vaccine
title_fullStr	Structural insights into global mutations in the ligand-binding domain of VAR2CSA and its implications on placental malaria vaccine
title_full_unstemmed	Structural insights into global mutations in the ligand-binding domain of VAR2CSA and its implications on placental malaria vaccine
title_sort	structural insights into global mutations in the ligand-binding domain of var2csa and its implications on placental malaria vaccine
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/4d93b7dffb8048b6804bbe02d5ef6b4c
work_keys_str_mv	AT jasmitagill structuralinsightsintoglobalmutationsintheligandbindingdomainofvar2csaanditsimplicationsonplacentalmalariavaccine AT soumyanandachakraborti structuralinsightsintoglobalmutationsintheligandbindingdomainofvar2csaanditsimplicationsonplacentalmalariavaccine AT praveenbharti structuralinsightsintoglobalmutationsintheligandbindingdomainofvar2csaanditsimplicationsonplacentalmalariavaccine AT amitsharma structuralinsightsintoglobalmutationsintheligandbindingdomainofvar2csaanditsimplicationsonplacentalmalariavaccine
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Structural insights into global mutations in the ligand-binding domain of VAR2CSA and its implications on placental malaria vaccine

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