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VAR2CSA

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https://www.readbyqxmd.com/read/29038124/plasmodium-falciparum-pfemp1-modulates-monocyte-macrophage-transcription-factor-activation-and-cytokine-and-chemokine-responses
#1
Natália Guimarães Sampaio, Emily Marie Eriksson, Louis Schofield
Immunity to Plasmodium falciparum malaria is slow to develop, and it is often asserted that malaria suppresses host immunity, although this is poorly understood and the molecular basis for such activity remains unknown. P. falciparum Erythrocyte Membrane Protein 1 (PfEMP1) is a virulence factor that plays a key role in parasite-host interactions. We investigated the immunosuppressive effect of PfEMP1 on monocytes/macrophages, which are central to the anti-parasitic innate response. RAW macrophages and human primary monocytes were stimulated with wild-type 3D7 or CS2 parasites or transgenic PfEMP1-null parasites...
October 16, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28962616/statistical-prediction-of-immunity-to-placental-malaria-based-on-multi-assay-antibody-data-for-malarial-antigens
#2
Chathura Siriwardhana, Rui Fang, Ali Salanti, Rose G F Leke, Naveen Bobbili, Diane Wallace Taylor, John J Chen
BACKGROUND: Plasmodium falciparum infections are especially severe in pregnant women because infected erythrocytes (IE) express VAR2CSA, a ligand that binds to placental trophoblasts, causing IE to accumulate in the placenta. Resulting inflammation and pathology increases a woman's risk of anemia, miscarriage, premature deliveries, and having low birthweight (LBW) babies. Antibodies (Ab) to VAR2CSA reduce placental parasitaemia and improve pregnancy outcomes. Currently, no single assay is able to predict if a woman has adequate immunity to prevent placental malaria (PM)...
September 29, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28893687/genetic-analysis-of-id1-dbl2x-predicts-its-validity-as-a-vaccine-candidate-in-colombia-and-supports-at-least-two-independently-introduced-plasmodium-falciparum-populations-in-the-region
#3
J Rajwani, C M Klinger, E Arango, M I Arroyo, A Sabbagh, A Maestre, J B Dacks, S Gnidehou, S K Yanow
Pregnancy-associated malaria (PAM) poses a threat to both the mother and fetus, increasing the risk of severe maternal anemia, fetal growth restriction and low birth weight infants. Two vaccines are currently in development to protect women from Plasmodium falciparum in pregnancy. Both vaccine constructs target the ID1-DBL2X domain of VAR2CSA, a protein expressed on the surface of infected erythrocytes (IEs) that mediates parasite sequestration in the placenta. Although development of an effective vaccine may be hampered by ID1-DBL2X polymorphisms expressed by field isolates, a recent study showed that genetic variation of this domain in South American parasite populations is much lower than in other geographical locations...
September 8, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28818101/a-new-method-for-sequencing-the-hypervariable-plasmodium-falciparum-gene-var2csa-from-clinical-samples
#4
Antoine Dara, Mark A Travassos, Matthew Adams, Sarah Schaffer DeRoo, Elliott F Drábek, Sonia Agrawal, Miriam K Laufer, Christopher V Plowe, Joana C Silva
BACKGROUND: VAR2CSA, a member of the Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family, mediates the binding of P. falciparum-infected erythrocytes to chondroitin sulfate A, a surface-associated molecule expressed in placental cells, and plays a central role in the pathogenesis of placental malaria. VAR2CSA is a target of naturally acquired immunity and, as such, is a leading vaccine candidate against placental malaria. This protein is very polymorphic and technically challenging to sequence...
August 17, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28801627/increased-risk-of-low-birth-weight-in-women-with-placental-malaria-associated-with-p-falciparum-var2csa-clade
#5
Jaymin C Patel, Nicholas J Hathaway, Christian M Parobek, Kyaw L Thwai, Mwayiwawo Madanitsa, Carole Khairallah, Linda Kalilani-Phiri, Victor Mwapasa, Achille Massougbodji, Nadine Fievet, Jeffery A Bailey, Feiko O Ter Kuile, Philippe Deloron, Stephanie M Engel, Steve M Taylor, Jonathan J Juliano, Nicaise Tuikue Ndam, Steven R Meshnick
Pregnancy associated malaria (PAM) causes adverse pregnancy and birth outcomes owing to Plasmodium falciparum accumulation in the placenta. Placental accumulation is mediated by P. falciparum protein VAR2CSA, a leading PAM-specific vaccine target. The extent of its antigen diversity and impact on clinical outcomes remain poorly understood. Through amplicon deep-sequencing placental malaria samples from women in Malawi and Benin, we assessed sequence diversity of VAR2CSA's ID1-DBL2x region, containing putative vaccine targets and estimated associations of specific clades with adverse birth outcomes...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28716094/an-analytical-approach-to-reduce-between-plate-variation-in-multiplex-assays-that-measure-antibodies-to-plasmodium-falciparum-antigens
#6
Rui Fang, Andrew Wey, Naveen K Bobbili, Rose F G Leke, Diane Wallace Taylor, John J Chen
BACKGROUND: Antibodies play an important role in immunity to malaria. Recent studies show that antibodies to multiple antigens, as well as, the overall breadth of the response are associated with protection from malaria. Yet, the variability and reliability of antibody measurements against a combination of malarial antigens using multiplex assays have not been well characterized. METHODS: A normalization procedure for reducing between-plate variation using replicates of pooled positive and negative controls was investigated...
July 17, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28715465/multiplexing-detection-of-igg-against-plasmodium-falciparum-pregnancy-specific-antigens
#7
Ana Maria Fonseca, Llorenç Quinto, Alfons Jiménez, Raquel González, Azucena Bardají, Sonia Maculuve, Carlota Dobaño, Maria Rupérez, Anifa Vala, John J Aponte, Esperanza Sevene, Eusebio Macete, Clara Menéndez, Alfredo Mayor
BACKGROUND: Pregnant women exposed to Plasmodium falciparum generate antibodies against VAR2CSA, the parasite protein that mediates adhesion of infected erythrocytes to the placenta. There is a need of high-throughput tools to determine the fine specificity of these antibodies that can be used to identify immune correlates of protection and exposure. Here we aimed at developing a multiplex-immunoassay to detect antibodies against VAR2CSA antigens. METHODS AND FINDINGS: We constructed two multiplex-bead arrays, one composed of 3 VAR2CSA recombinant-domains (DBL3X, DBL5Ɛ and DBL6Ɛ) and another composed of 46 new peptides covering VAR2CSA conserved and semi-conserved regions...
2017: PloS One
https://www.readbyqxmd.com/read/28698275/crispr-cas9-genome-editing-reveals-that-the-intron-is-not-essential-for-var2csa-gene-activation-or-silencing-in-plasmodium-falciparum
#8
Jessica M Bryant, Clément Regnault, Christine Scheidig-Benatar, Sebastian Baumgarten, Julien Guizetti, Artur Scherf
Plasmodium falciparum relies on monoallelic expression of 1 of 60 var virulence genes for antigenic variation and host immune evasion. Each var gene contains a conserved intron which has been implicated in previous studies in both activation and repression of transcription via several epigenetic mechanisms, including interaction with the var promoter, production of long noncoding RNAs (lncRNAs), and localization to repressive perinuclear sites. However, functional studies have relied primarily on artificial expression constructs...
July 11, 2017: MBio
https://www.readbyqxmd.com/read/28527688/clinical-development-of-a-var2csa-based-placental-malaria-vaccine-pamvac-quantifying-vaccine-antigen-specific-memory-b-t-cell-activity-in-beninese-primigravidae
#9
Komi Gbédandé, Nadine Fievet, Firmine Viwami, Sem Ezinmegnon, Saadou Issifou, Jean-Philippe Chippaux, Yannelle Dossou, Kabirou Moutairou, Achille Massougbodji, Nicaise Ndam, Willem Adriaan de Jongh, T Max M Søgaard, Ali Salanti, Morten A Nielsen, Meral Esen, Benjamin Mordmüller, Philippe Deloron, Adrian J F Luty
BACKGROUND: The antigen VAR2CSA plays a pivotal role in the pathophysiology of pregnancy-associated malaria (PAM) caused by Plasmodium falciparum. A VAR2CSA-based vaccine candidate, PAMVAC, is under development by an EU-funded multi-country consortium (PlacMalVac project). As part of PAMVAC's clinical development, we quantified naturally acquired vaccine antigen-specific memory B and T cell responses in Beninese primigravidae recruited at the beginning of pregnancy and followed up to delivery and beyond...
May 17, 2017: Vaccine
https://www.readbyqxmd.com/read/28481333/regulation-of-pfemp1-var2csa-translation-by-a-plasmodium-translation-enhancing-factor
#10
Sherwin Chan, Alejandra Frasch, Chandra Sekhar Mandava, Jun-Hong Ch'ng, Maria Del Pilar Quintana, Mattias Vesterlund, Mehdi Ghorbal, Nicolas Joannin, Oscar Franzén, Jose-Juan Lopez-Rubio, Sonia Barbieri, Antonio Lanzavecchia, Suparna Sanyal, Mats Wahlgren
Pregnancy-associated malaria commonly involves the binding of Plasmodium falciparum-infected erythrocytes to placental chondroitin sulfate A (CSA) through the PfEMP1-VAR2CSA protein. VAR2CSA is translationally repressed by an upstream open reading frame. In this study, we report that the P. falciparum translation enhancing factor (PTEF) relieves upstream open reading frame repression and thereby facilitates VAR2CSA translation. VAR2CSA protein levels in var2csa-transcribing parasites are dependent on the expression level of PTEF, and the alleviation of upstream open reading frame repression requires the proteolytic processing of PTEF by PfCalpain...
May 8, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28408175/an-oncofetal-glycosaminoglycan-modification-provides-therapeutic-access-to-cisplatin-resistant-bladder-cancer
#11
Roland Seiler, Htoo Zarni Oo, Davide Tortora, Thomas M Clausen, Chris K Wang, Gunjan Kumar, Marina Ayres Pereira, Maj S Ørum-Madsen, Mette Ø Agerbæk, Tobias Gustavsson, Mie A Nordmaj, Jamie R Rich, Nada Lallous, Ladan Fazli, Sherry S Lee, James Douglas, Tilman Todenhöfer, Shaghayegh Esfandnia, Dulguun Battsogt, John S Babcook, Nader Al-Nakouzi, Simon J Crabb, Igor Moskalev, Bernhard Kiss, Elai Davicioni, George N Thalmann, Paul S Rennie, Peter C Black, Ali Salanti, Mads Daugaard
BACKGROUND: Although cisplatin-based neoadjuvant chemotherapy (NAC) improves survival of unselected patients with muscle-invasive bladder cancer (MIBC), only a minority responds to therapy and chemoresistance remains a major challenge in this disease setting. OBJECTIVE: To investigate the clinical significance of oncofetal chondroitin sulfate (ofCS) glycosaminoglycan chains in cisplatin-resistant MIBC and to evaluate these as targets for second-line therapy. DESIGN, SETTING, AND PARTICIPANTS: An ofCS-binding recombinant VAR2CSA protein derived from the malaria parasite Plasmodium falciparum (rVAR2) was used as an in situ, in vitro, and in vivo ofCS-targeting reagent in cisplatin-resistant MIBC...
July 2017: European Urology
https://www.readbyqxmd.com/read/28351419/new-var-reconstruction-algorithm-exposes-high-var-sequence-diversity-in-a-single-geographic-location-in-mali
#12
Antoine Dara, Elliott F Drábek, Mark A Travassos, Kara A Moser, Arthur L Delcher, Qi Su, Timothy Hostelley, Drissa Coulibaly, Modibo Daou, Ahmadou Dembele, Issa Diarra, Abdoulaye K Kone, Bourema Kouriba, Matthew B Laurens, Amadou Niangaly, Karim Traore, Youssouf Tolo, Claire M Fraser, Mahamadou A Thera, Abdoulaye A Djimde, Ogobara K Doumbo, Christopher V Plowe, Joana C Silva
BACKGROUND: Encoded by the var gene family, highly variable Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP1) proteins mediate tissue-specific cytoadherence of infected erythrocytes, resulting in immune evasion and severe malaria disease. Sequencing and assembling the 40-60 var gene complement for individual infections has been notoriously difficult, impeding molecular epidemiological studies and the assessment of particular var elements as subunit vaccine candidates. METHODS: We developed and validated a novel algorithm, Exon-Targeted Hybrid Assembly (ETHA), to perform targeted assembly of var gene sequences, based on a combination of Pacific Biosciences and Illumina data...
March 28, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28148260/individuals-living-in-a-malaria-endemic-area-of-cameroon-do-not-have-an-acquired-antibody-response-to-plasmodium-falciparum-histidine-rich-protein-2
#13
Diane Wallace Taylor, Naveen Bobbili, Vedbar S Khadka, Isabella A Quakyi, Rose G F Leke
BACKGROUND: Diagnosis of Plasmodium falciparum is often based on detection of histidine-rich protein 2 (HRP2) in blood. Most HRP2-based assays have high sensitivity and specificity; however, authors have suggested that antibodies (Ab) to HRP2 could reduce assay sensitivity. This study sought to characterize the antibody response to HRP2 with respect to prevalence, class, subclass, affinity, and age distribution in Cameroonian children and adults residing in an area with high P. falciparum transmission...
February 1, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28131394/novel-adenovirus-encoded-virus-like-particles-displaying-the-placental-malaria-associated-var2csa-antigen
#14
Anne-Marie C Andersson, Mafalda Resende, Ali Salanti, Morten A Nielsen, Peter J Holst
The malaria parasite Plasmodium falciparum presents antigens on the infected erythrocyte surface that bind human receptors expressed on the vascular endothelium. The VAR2CSA mediated binding to a distinct chondroitin sulphate A (CSA) is a crucial step in the pathophysiology of placental malaria and the CSA binding region of VAR2CSA has been identified as a promising vaccine target against placental malaria. Here we designed adenovirus encoded virus-like particles (VLP) by co-encoding Simian Immunodeficiency Virus (SIV) gag and VAR2CSA...
February 22, 2017: Vaccine
https://www.readbyqxmd.com/read/28012775/comparison-of-functional-assays-used-in-the-clinical-development-of-a-placental-malaria-vaccine
#15
Caroline Pehrson, Kristine K Heno, Yvonne Adams, Mafalda Resende, Line Mathiesen, Max Soegaard, Willem A de Jongh, Thor G Theander, Ali Salanti, Morten A Nielsen
BACKGROUND: Malaria in pregnancy is associated with significant morbidity in pregnant women and their offspring. Plasmodium falciparum infected erythrocytes (IE) express VAR2CSA that mediates binding to chondroitin sulphate A (CSA) in the placenta. Two VAR2CSA-based vaccines for placental malaria are in clinical development. The purpose of this study was to evaluate the robustness and comparability of binding inhibition assays used in the clinical development of placental malaria vaccines...
December 21, 2016: Vaccine
https://www.readbyqxmd.com/read/27997697/burkitt-lymphoma-expresses-oncofetal-chondroitin-sulfate-without-being-a-reservoir-for-placental-malaria-sequestration
#16
Mette Ø Agerbaek, Marina A Pereira, Thomas M Clausen, Caroline Pehrson, Htoo Zarni Oo, Charlotte Spliid, Jamie R Rich, Vincent Fung, Francis Nkrumah, Janet Neequaye, Robert J Biggar, Steven J Reynolds, Giovanna Tosato, Sheeja T Pullarkat, Leona W Ayers, Thor G Theander, Mads Daugaard, Kishor Bhatia, Morten A Nielsen, Sam M Mbulaiteye, Ali Salanti
Burkitt lymphoma (BL) is a malignant disease, which is frequently found in areas with holoendemic Plasmodium falciparum malaria. We have previously found that the VAR2CSA protein is present on malaria-infected erythrocytes and facilitates a highly specific binding to the placenta. ofCS is absent in other non-malignant tissues and thus VAR2CSA generally facilitates parasite sequestration and accumulation in pregnant women. In this study, we show that the specific receptor for VAR2CSA, the oncofetal chondroitin sulfate (ofCS), is likewise present in BL tissue and cell lines...
April 1, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27900573/erratum-to-molecular-dissection-of-placental-malaria-protein-var2csa-interaction-with-a-chemo-enzymatically-synthesized-chondroitin-sulfate-library
#17
Nobuo Sugiura, Thomas Mandel Clausen, Tatsumasa Shioiri, Tobias Gustavsson, Hideto Watanabe, Ali Salanti
No abstract text is available yet for this article.
December 2016: Glycoconjugate Journal
https://www.readbyqxmd.com/read/27814765/antibody-responses-to-the-full-length-var2csa-and-its-dbl-domains-in-cameroonian-children-and-teenagers
#18
Barriere A Y Fodjo, Njika Atemnkeng, Livo Esemu, Emile K Yuosembom, Isabella A Quakyi, Viviane H M Tchinda, Joseph Smith, Ali Salanti, Jude Bigoga, Diane W Taylor, Rose G F Leke, Anna Babakhanyan
BACKGROUND: Antigenic variation of Plasmodium falciparum erythrocyte membrane protein 1 is a key parasite mechanism for immune evasion and parasite survival. It is assumed that the number of parasites expressing the same var gene must reach high enough numbers before the host can produce detectable levels of antibodies (Ab) to the variant. VAR2CSA is a protein coded for by one of 60 var genes that is expressed on the surface of infected erythrocytes (IE) and mediates IE binding to the placenta...
November 4, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27773760/preferential-expression-of-domain-cassettes-4-8-and-13-of-plasmodium-falciparum-erythrocyte-membrane-protein-1-in-severe-malaria-imported-in-france
#19
N Argy, G I Bertin, J Milet, V Hubert, J Clain, S Cojean, P Houzé, N Tuikue-Ndam, E Kendjo, P Deloron, S Houzé
OBJECTIVES: Severe Plasmodium falciparum malaria (SM) involves cytoadhesion of parasitized red blood cells, mediated by P. falciparum erythrocyte membrane protein 1, which is encoded by var genes. Expression of var gene group A and B or encoding domain cassettes DC4, DC5, DC8 and DC13 has been implicated in SM in African children, but no data exist in the context of imported malaria. The aim of this study was to investigate var gene expression linked to clinical presentation and host factors in SM imported into France...
March 2017: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/27655130/oncofetal-chondroitin-sulfate-glycosaminoglycans-are-key-players-in-integrin-signaling-and-tumor-cell-motility
#20
Thomas Mandel Clausen, Marina Ayres Pereira, Nader Al Nakouzi, Htoo Zarni Oo, Mette Ø Agerbæk, Sherry Lee, Maj Sofie Ørum-Madsen, Anders Riis Kristensen, Amal El-Naggar, Paul M Grandgenett, Jean L Grem, Michael A Hollingsworth, Peter J Holst, Thor Theander, Poul H Sorensen, Mads Daugaard, Ali Salanti
Many tumors express proteoglycans modified with oncofetal chondroitin sulfate glycosaminoglycan chains (ofCS), which are normally restricted to the placenta. However, the role of ofCS in cancer is largely unknown. The function of ofCS in cancer was analyzed using the recombinant ofCS-binding VAR2CSA protein (rVAR2) derived from the malaria parasite, Plasmodium falciparum We demonstrate that ofCS plays a key role in tumor cell motility by affecting canonical integrin signaling pathways. Binding of rVAR2 to tumor cells inhibited the interaction of cells with extracellular matrix (ECM) components, which correlated with decreased phosphorylation of Src kinase...
December 2016: Molecular Cancer Research: MCR
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