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https://www.readbyqxmd.com/read/27900573/erratum-to-molecular-dissection-of-placental-malaria-protein-var2csa-interaction-with-a-chemo-enzymatically-synthesized-chondroitin-sulfate-library
#1
Nobuo Sugiura, Thomas Mandel Clausen, Tatsumasa Shioiri, Tobias Gustavsson, Hideto Watanabe, Ali Salanti
No abstract text is available yet for this article.
November 30, 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
#2
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
#3
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...
October 20, 2016: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/27655130/oncofetal-chondroitin-sulfate-glycosaminoglycans-are-key-players-in-integrin-signaling-and-tumor-cell-motility
#4
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...
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
#5
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
#6
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
#7
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...
June 10, 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
#8
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...
2016: Malaria Journal
https://www.readbyqxmd.com/read/27190180/var2csa-domain-specific-analysis-of-naturally-acquired-functional-antibodies-to-plasmodium-falciparum-placental-malaria
#9
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
#10
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...
2016: Journal of Nanobiotechnology
https://www.readbyqxmd.com/read/27045035/murine-model-for-preclinical-studies-of-var2csa-mediated-pathology-associated-with-malaria-in-pregnancy
#11
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
#12
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
https://www.readbyqxmd.com/read/26626275/comparison-of-the-specificity-of-antibodies-to-var2csa-in-cameroonian-multigravidae-with-and-without-placental-malaria-a-retrospective-case-control-study
#13
COMPARATIVE STUDY
Anna Babakhanyan, Rui Fang, Andrew Wey, Ali Salanti, Grace Sama, Canisia Efundem, Robert J I Leke, John J Chen, Rose G F Leke, Diane W Taylor
BACKGROUND: Antibodies (Ab) to VAR2CSA prevent Plasmodium falciparum-infected erythrocytes from sequestrating in the placenta, i.e., prevent placental malaria (PM). The specificity of Ab to VAR2CSA associated with absence of PM is unknown. Accordingly, differences in the specificity of Ab to VAR2CSA were compared between multigravidae with and without PM who had Ab to VAR2CSA. METHODS: In a retrospective case-control study, plasma collected from Cameroonian multigravidae with (n = 96) and without (n = 324) PM were screened in 21 assays that measured antibody levels to full length VAR2CSA (FV2), individual VAR2CSA DBL domains, VAR2CSA domains from different genetic backgrounds (variants), as well as proportion of high avidity Ab to FV2...
December 1, 2015: Malaria Journal
https://www.readbyqxmd.com/read/26599509/a-novel-virus-like-particle-based-vaccine-platform-displaying-the-placental-malaria-antigen-var2csa
#14
Susan Thrane, Christoph M Janitzek, Mette Ø Agerbæk, Sisse B Ditlev, Mafalda Resende, Morten A Nielsen, Thor G Theander, Ali Salanti, Adam F Sander
Placental malaria caused by Plasmodium falciparum is a major cause of mortality and severe morbidity. Clinical testing of a soluble protein-based vaccine containing the parasite ligand, VAR2CSA, has been initiated. VAR2CSA binds to the human receptor chondroitin sulphate A (CSA) and is responsible for sequestration of Plasmodium falciparum infected erythrocytes in the placenta. It is imperative that a vaccine against malaria in pregnancy, if administered to women before they become pregnant, can induce a strong and long lasting immune response...
2015: PloS One
https://www.readbyqxmd.com/read/26469717/designing-a-var2csa-based-vaccine-to-prevent-placental-malaria
#15
REVIEW
Michal Fried, Patrick E Duffy
Placental malaria (PM) due to Plasmodium falciparum is a major cause of maternal, fetal and infant mortality, but the mechanisms of pathogenesis and protective immunity are relatively well-understood for this condition, providing a path for vaccine development. P. falciparum parasites bind to chondroitin sulfate A (CSA) to sequester in the placenta, and women become resistant over 1-2 pregnancies as they acquire antibodies that block adhesion to CSA. The protein VAR2CSA, a member of the PfEMP1 variant surface antigen family, mediates parasite adhesion to CSA, and is the leading target for a vaccine to prevent PM...
December 22, 2015: Vaccine
https://www.readbyqxmd.com/read/26461094/targeting-human-cancer-by-a-glycosaminoglycan-binding-malaria-protein
#16
Ali Salanti, Thomas M Clausen, Mette Ø Agerbæk, Nader Al Nakouzi, Madeleine Dahlbäck, Htoo Z Oo, Sherry Lee, Tobias Gustavsson, Jamie R Rich, Bradley J Hedberg, Yang Mao, Line Barington, Marina A Pereira, Janine LoBello, Makoto Endo, Ladan Fazli, Jo Soden, Chris K Wang, Adam F Sander, Robert Dagil, Susan Thrane, Peter J Holst, Le Meng, Francesco Favero, Glen J Weiss, Morten A Nielsen, Jim Freeth, Torsten O Nielsen, Joseph Zaia, Nhan L Tran, Jeff Trent, John S Babcook, Thor G Theander, Poul H Sorensen, Mads Daugaard
Plasmodium falciparum engineer infected erythrocytes to present the malarial protein, VAR2CSA, which binds a distinct type chondroitin sulfate (CS) exclusively expressed in the placenta. Here, we show that the same CS modification is present on a high proportion of malignant cells and that it can be specifically targeted by recombinant VAR2CSA (rVAR2). In tumors, placental-like CS chains are linked to a limited repertoire of cancer-associated proteoglycans including CD44 and CSPG4. The rVAR2 protein localizes to tumors in vivo and rVAR2 fused to diphtheria toxin or conjugated to hemiasterlin compounds strongly inhibits in vivo tumor cell growth and metastasis...
October 12, 2015: Cancer Cell
https://www.readbyqxmd.com/read/26450557/structure-of-the-dbl3x-dbl4%C3%AE%C2%B5-region-of-the-var2csa-placental-malaria-vaccine-candidate-insight-into-dbl-domain-interactions
#17
Stéphane Gangnard, Anita Lewit-Bentley, Sébastien Dechavanne, Anand Srivastava, Faroudja Amirat, Graham A Bentley, Benoît Gamain
The human malaria parasite, Plasmodium falciparum, is able to evade spleen-mediated clearing from blood stream by sequestering in peripheral organs. This is due to the adhesive properties conferred by the P. falciparum Erythrocyte Membrane Protein 1 (PfEMP1) family exported by the parasite to the surface of infected erythrocytes. Expression of the VAR2CSA variant of PfEMP1 leads to pregnancy-associated malaria, which occurs when infected erythrocytes massively sequester in the placenta by binding to low-sulfated Chondroitin Sulfate A (CSA) present in the intervillous spaces...
2015: Scientific Reports
https://www.readbyqxmd.com/read/26450394/high-throughput-testing-of-antibody-dependent-binding-inhibition-of-placental-malaria-parasites
#18
Morten A Nielsen, Ali Salanti
The particular virulence of Plasmodium falciparum manifests in diverse severe malaria syndromes as cerebral malaria, severe anemia and placental malaria. The cause of both the severity and the diversity of infection outcome, is the ability of the infected erythrocyte (IE) to bind a range of different human receptors through Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) on the surface of the infected cell. As the var genes encoding the large PfEMP1 antigens are extensively polymorphic, vaccine development strategies are focused on targeting the functional binding epitopes...
2015: Methods in Molecular Biology
https://www.readbyqxmd.com/read/26450393/evaluation-of-pregnancy-malaria-vaccine-candidates-the-binding-inhibition-assay
#19
Tracy Saveria, Patrick E Duffy, Michal Fried
The parasite-binding inhibition assay is designed to evaluate the acquisition of naturally acquired functional antibodies that block Plasmodium falciparum binding to endothelial or placental receptors. The assay is also used to assess functional activity by antibodies induced by immunization, for example antibodies raised against pregnancy malaria vaccine candidates like VAR2CSA. Here we describe a plate-based assay to measure the levels of adhesion-blocking antibodies. This assay format can be adapted to any lab that is minimally equipped for short-term parasite culture...
2015: Methods in Molecular Biology
https://www.readbyqxmd.com/read/26393516/identification-of-a-major-dimorphic-region-in-the-functionally-critical-n-terminal-id1-domain-of-var2csa
#20
Justin Doritchamou, Audrey Sabbagh, Jakob S Jespersen, Emmanuelle Renard, Ali Salanti, Morten A Nielsen, Philippe Deloron, Nicaise Tuikue Ndam
The VAR2CSA protein of Plasmodium falciparum is transported to and expressed on the infected erythrocyte surface where it plays a key role in placental malaria (PM). It is the current leading candidate for a vaccine to prevent PM. However, the antigenic polymorphism integral to VAR2CSA poses a challenge for vaccine development. Based on detailed analysis of polymorphisms in the sequence of its ligand-binding N-terminal region, currently the main focus for vaccine development, we assessed var2csa from parasite isolates infecting pregnant women...
2015: PloS One
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