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VAR2CSA

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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
#1
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
#2
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
#3
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...
April 10, 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
#4
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
#5
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
#6
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...
January 25, 2017: Vaccine
https://www.readbyqxmd.com/read/28012775/comparison-of-functional-assays-used-in-the-clinical-development-of-a-placental-malaria-vaccine
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/27653505/infections-with-plasmodium-falciparum-during-pregnancy-affect-var2csa-dbl-5-domain-specific-t-cell-cytokine-responses
#13
Komi Gbédandé, Gilles Cottrell, Bertin Vianou, Samad Ibitokou, Aurax Fernando, Marita Troye-Blomberg, Ali Salanti, Kabirou Moutairou, Achille Massougbodji, Nicaise Tuikue Ndam, Philippe Deloron, Adrian J F Luty, Nadine Fievet
BACKGROUND: Current knowledge of human immunological responses to pregnancy-associated malaria-specific Plasmodium falciparum protein VAR2CSA concerns almost exclusively B cell-driven antibody-mediated activity. Knowledge of VAR2CSA-specific T cell-mediated activity is minimal by comparison, with only a single published report of a study investigating VAR2CSA-derived peptide-specific T cell responses. The study described here represents an attempt to redress this balance. METHODS: Within the framework of a cohort study of 1037 pregnant Beninese, sub-groups were selected on the basis of the documented presence/absence of infection with P...
2016: Malaria Journal
https://www.readbyqxmd.com/read/27556547/placental-sequestration-of-plasmodium-falciparum-malaria-parasites-is-mediated-by-the-interaction-between-var2csa-and-chondroitin-sulfate-a-on-syndecan-1
#14
Marina Ayres Pereira, Thomas Mandel Clausen, Caroline Pehrson, Yang Mao, Mafalda Resende, Mads Daugaard, Anders Riis Kristensen, Charlotte Spliid, Line Mathiesen, Lisbeth E Knudsen, Peter Damm, Thor G Theander, Stefan R Hansson, Morten A Nielsen, Ali Salanti
During placental malaria, Plasmodium falciparum infected erythrocytes sequester in the placenta, causing health problems for both the mother and fetus. The specific adherence is mediated by the VAR2CSA protein, which binds to placental chondroitin sulfate (CS) on chondroitin sulfate proteoglycans (CSPGs) in the placental syncytium. However, the identity of the CSPG core protein and the cellular impact of the interaction have remain elusive. In this study we identified the specific CSPG core protein to which the CS is attached, and characterized its exact placental location...
August 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27287227/molecular-dissection-of-placental-malaria-protein-var2csa-interaction-with-a-chemo-enzymatically-synthesized-chondroitin-sulfate-library
#15
Nobuo Sugiura, Thomas Mandel Clausen, Tatsumasa Shioiri, Tobias Gustavsson, Hideto Watanabe, Ali Salanti
Placental malaria, a serious infection caused by the parasite Plasmodium falciparum, is characterized by the selective accumulation of infected erythrocytes (IEs) in the placentas of the pregnant women. Placental adherence is mediated by the malarial VAR2CSA protein, which interacts with chondroitin sulfate (CS) proteoglycans present in the placental tissue. CS is a linear acidic polysaccharide composed of repeating disaccharide units of D-glucuronic acid and N-acetyl-D-galactosamine that are modified by sulfate groups at different positions...
December 2016: Glycoconjugate Journal
https://www.readbyqxmd.com/read/27230523/adhesion-of-plasmodium-falciparum-infected-erythrocytes-in-ex-vivo-perfused-placental-tissue-a-novel-model-of-placental-malaria
#16
Caroline Pehrson, Line Mathiesen, Kristine K Heno, Ali Salanti, Mafalda Resende, Ron Dzikowski, Peter Damm, Stefan R Hansson, Christopher L King, Henning Schneider, Christian W Wang, Thomas Lavstsen, Thor G Theander, Lisbeth E Knudsen, Morten A Nielsen
BACKGROUND: Placental malaria occurs when Plasmodium falciparum infected erythrocytes sequester in the placenta. Placental parasite isolates bind to chondroitin sulphate A (CSA) by expression of VAR2CSA on the surface of infected erythrocytes, but may sequester by other VAR2CSA mediated mechanisms, such as binding to immunoglobulins. Furthermore, other parasite antigens have been associated with placental malaria. These findings have important implications for placental malaria vaccine design...
May 26, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27190180/var2csa-domain-specific-analysis-of-naturally-acquired-functional-antibodies-to-plasmodium-falciparum-placental-malaria
#17
Justin Yai Alamou Doritchamou, Raul Herrera, Joan A Aebig, Robert Morrison, Vu Nguyen, Karine Reiter, Richard L Shimp, Nicholas J MacDonald, David L Narum, Michal Fried, Patrick E Duffy
BACKGROUND: Placental malaria is caused by Plasmodium falciparum-infected erythrocytes (IEs) that surface-express VAR2CSA and bind chondroitin sulfate A. The inflammatory response to placenta-sequestered parasites is associated with poor pregnancy outcomes, and protection may be mediated in part by VAR2CSA antibodies that block placental IE adhesion. METHODS: In this study, we used a new approach to assess VAR2CSA domains for functional epitopes recognized by naturally acquired antibodies...
August 15, 2016: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/27117585/bacterial-superglue-enables-easy-development-of-efficient-virus-like-particle-based-vaccines
#18
Susan Thrane, Christoph M Janitzek, Sungwa Matondo, Mafalda Resende, Tobias Gustavsson, Willem Adriaan de Jongh, Stine Clemmensen, Will Roeffen, Marga van de Vegte-Bolmer, Geert Jan van Gemert, Robert Sauerwein, John T Schiller, Morten A Nielsen, Thor G Theander, Ali Salanti, Adam F Sander
BACKGROUND: Virus-like particles (VLPs) represent a significant advance in the development of subunit vaccines, combining high safety and efficacy. Their particulate nature and dense repetitive subunit organization makes them ideal scaffolds for display of vaccine antigens. Traditional approaches for VLP-based antigen display require labor-intensive trial-and-error optimization, and often fail to generate dense antigen display. Here we utilize the split-intein (SpyTag/SpyCatcher) conjugation system to generate stable isopeptide bound antigen-VLP complexes by simply mixing of the antigen and VLP components...
April 27, 2016: Journal of Nanobiotechnology
https://www.readbyqxmd.com/read/27045035/murine-model-for-preclinical-studies-of-var2csa-mediated-pathology-associated-with-malaria-in-pregnancy
#19
Luciana V de Moraes, Sebastien Dechavanne, Patrícia M Sousa, André Barateiro, Sónia F Cunha, Sofia Nunes-Silva, Flávia A Lima, Oscar Murillo, Claudio R F Marinho, Stephane Gangnard, Anand Srivastava, Joanna A Braks, Chris J Janse, Benoit Gamain, Blandine Franke-Fayard, Carlos Penha-Gonçalves
Plasmodium falciparum infection during pregnancy leads to abortions, stillbirth, low birth weight, and maternal mortality. Infected erythrocytes (IEs) accumulate in the placenta by adhering to chondroitin sulfate A (CSA) via var2CSA protein exposed on the P. falciparum IE membrane. Plasmodium berghei IE infection in pregnant BALB/c mice is a model for severe placental malaria (PM). Here, we describe a transgenic P. berghei parasite expressing the full-length var2CSA extracellular region (domains DBL1X to DBL6ε) fused to a P...
June 2016: Infection and Immunity
https://www.readbyqxmd.com/read/26711513/influence-of-intermittent-preventive-treatment-on-antibodies-to-var2csa-in-pregnant-cameroonian-women
#20
Anna Babakhanyan, Yeung L Tutterrow, Naveen Bobbili, Ali Salanti, Andrew Wey, Josephine Fogako, Robert J Leke, Rose G F Leke, Diane Wallace Taylor
Intermittent preventive treatment (IPT) and insecticide-treated bed nets are the standard of care for preventing malaria in pregnant women. Since these preventive measures reduce exposure to malaria, their influence on the antibody (Ab) response to the parasite antigen VAR2CSA was evaluated in pregnant Cameroonian women exposed to holoendemic malaria. Ab levels to full-length VAR2CSA (FV2), variants of the six Duffy binding like (DBL) domains, and proportion of high avidity Ab to FV2 were measured longitudinally in 92 women before and 147 women after IPT...
March 2016: American Journal of Tropical Medicine and Hygiene
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