A5090557161- Malaria Research and Control
- Complement system in diseases
- Proteoglycans and glycosaminoglycans research
- Mosquito-borne diseases and control
- Glycosylation and Glycoproteins Research
- HIV Research and Treatment
- Research on Leishmaniasis Studies
- Monoclonal and Polyclonal Antibodies Research
- vaccines and immunoinformatics approaches
- Cell Adhesion Molecules Research
- SARS-CoV-2 and COVID-19 Research
- Immunotherapy and Immune Responses
- Drug Transport and Resistance Mechanisms
- Trypanosoma species research and implications
- Cancer Cells and Metastasis
- Pregnancy and preeclampsia studies
- RNA Interference and Gene Delivery
- Hepatitis C virus research
- Invertebrate Immune Response Mechanisms
- Hepatitis Viruses Studies and Epidemiology
- Cancer Genomics and Diagnostics
- Osteoarthritis Treatment and Mechanisms
- Parasites and Host Interactions
- Influenza Virus Research Studies
- Fibroblast Growth Factor Research
University of Copenhagen
2016-2025
Ferring Pharmaceuticals (Denmark)
2024-2025
Copenhagen University Hospital
2015-2024
Sanquin
2023
Utrecht University
2023
Hvidovre Hospital
2023
ExpreS2ion Biotechnologies (Denmark)
2023
Rigshospitalet
2012-2022
University of British Columbia
2017
Université de Yaoundé I
2015
Summary Cytoadhesion of infected red blood cells (iRBC) is mediated through parasite‐encoded, clonally variant surface antigens (VSA) and a central process in the pathogenesis Plasmodium falciparum malaria. Pregnancy‐associated malaria (PAM) has been linked to VSA‐mediated adhesion iRBC glycosaminoglycan chondroitin sulphate A (CSA) placental intervillous space. Several studies have pointed members PfEMP1 VSA family as mediators CSA‐specific sequestration placenta. Here, we report marked...
In Plasmodium falciparum-endemic areas, pregnancy-associated malaria (PAM) is an important health problem. The condition precipitated by accumulation of parasite-infected erythrocytes (IEs) in the placenta, and this process mediated parasite-encoded variant surface antigens (VSA) binding to chondroitin sulfate A (CSA). Parasites causing PAM express unique VSA types, VSAPAM, which can be serologically classified as sex specific parity dependent. It because men from malaria-endemic areas do...
Virus-like particles (VLPs) represent a significant advance in the development of subunit vaccines, combining high safety and efficacy. Their particulate nature dense repetitive organization makes them ideal scaffolds for display vaccine antigens. Traditional approaches VLP-based antigen require labor-intensive trial-and-error optimization, often fail to generate display. Here we utilize split-intein (SpyTag/SpyCatcher) conjugation system stable isopeptide bound antigen-VLP complexes by...
Abstract The rapid development of a SARS-CoV-2 vaccine is global priority. Here, we develop two capsid-like particle (CLP)-based vaccines displaying the receptor-binding domain (RBD) spike protein. RBD antigens are displayed on AP205 CLPs through split-protein Tag/Catcher, ensuring unidirectional and high-density display RBD. Both soluble recombinant bind ACE2 receptor with nanomolar affinity. Mice vaccinated or CLP-displayed RBD, formulated in Squalene-Water-Emulsion. RBD-CLP induce higher...
The variant surface antigen family Plasmodium falciparum erythrocyte membrane protein-1 (PfEMP1) is an important target for protective immunity and implicated in the pathology of malaria through its ability to adhere host endothelial receptors. sequence diversity organization 3D7 PfEMP1 repertoire was investigated on basis complete genome sequence. Using two tree-building methods we analysed coding non-coding sequences var rif genes as well other parasite strains. can be sub-grouped into...
Parasite-encoded variant surface antigens (VSAs) like the var gene–encoded Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family are responsible for antigenic variation and infected red blood cell (RBC) cytoadhesion in P. malaria. Parasites causing severe malaria nonimmune patients tend to express a restricted subset of VSA (VSASM) that differs from associated with uncomplicated asymptomatic infection (VSAUM). We compared gene transcription unselected clone 3D7 expressing...
Plasmodium falciparum parasites that bind to chondroitin sulphate A (CSA) express unique variant surface antigens are involved in the placental sequestration precipitates pregnancy-associated malaria (PAM). Two var gene subfamilies, var1csa and var2csa have been associated with CSA binding. We show here P. isolates highly transcribed but not var1csa. was or only minimally by isolated from nonpregnant women. Placental effectively bound proteoglycans higher levels of var2csa. In pregnant...
Malaria is a major global health problem. Pregnant women are susceptible to infection regardless of previously acquired immunity. Placental malaria caused by parasites capable sequestering in the placenta. This mediated VAR2CSA, parasite antigen that interacts with chondroitin sulfate A (CSA). One vaccine strategy block this interaction VAR2CSA-specific antibodies. It priority define small VAR2CSA fragment can be used an adhesion blocking vaccine. In this, obvious approach regions involved...
Abstract Isolation of metastatic circulating tumor cells (CTCs) from cancer patients is high value for disease monitoring and molecular characterization. Despite the development many new CTC isolation platforms in last decade, their detection has remained a challenge due to lack specific sensitive markers. In this feasibility study, we present method based on binding malaria rVAR2 protein oncofetal chondroitin sulfate (ofCS). We show that efficiently captures CTCs hepatic, lung, pancreatic,...
Malaria in pregnancy has major impacts on mother and child health. To complement existing interventions, such as intermittent preventive treatment use of impregnated bed nets, we developed a malaria vaccine candidate with the aim reducing sequestration asexual "blood-stage" parasites placenta, virulence mechanism.The PAMVAC is based recombinant fragment VAR2CSA, Plasmodium falciparum protein responsible for binding to placenta via chondroitin sulfate A (CSA). Healthy, adult malaria-naive...
Overexpression of human epidermal growth factor receptor-2 (HER2) occurs in 20-30% invasive breast cancers. Monoclonal antibody therapy is effective treating HER2-driven mammary carcinomas, but its utility limited by high costs, side effects and development resistance. Active vaccination may represent a safer, more cheaper alternative, although the induction strong durable autoantibody responses hampered immune-tolerogenic mechanisms. Using novel virus-like particle (VLP) based vaccine...
During placental malaria, Plasmodium falciparum infected erythrocytes sequester in the placenta, causing health problems for both mother and fetus. The specific adherence is mediated by VAR2CSA protein, which binds to chondroitin sulfate (CS) on proteoglycans (CSPGs) syncytium. However, identity of CSPG core protein cellular impact interaction have remain elusive. In this study we identified CS attached, characterized its exact location. pull-down experiments using extracts from whole...
Enveloped viruses hijack not only the host translation processes, but also its glycosylation machinery, and to a variable extent cover viral surface proteins with tolerogenic host-like structures. SARS-CoV-2 protein S presents as trimer on is covered by dense shield of N-linked glycans, few O-glycosites have been reported. The location O-glycans controlled large family initiating enzymes expression in cells tissues hence difficult predict. Here, we used our well-established O-glycoproteomic...
Cancer mortality is exacerbated by late-stage diagnosis. Liquid biopsies based on genomic biomarkers can noninvasively diagnose cancers. However, validation studies have reported ~10% sensitivity to detect stage I cancer in a screening population and specific types, such as brain or genitourinary tumors, remain undetectable. We investigated urine plasma free glycosaminoglycan profiles (GAGomes) tumor metabolism for multi-cancer early detection (MCED) of 14 types using 2,064 samples from...
Capsid virus-like particles (cVLP) have proven safe and immunogenic can be a versatile platform to counter pandemics. We aimed clinically test modular cVLP COVID-19 vaccine in individuals who were naive SARS-CoV-2.In this phase 1, single-centre, dose-escalation, adjuvant-selection, open-label clinical trial, we recruited participants at the Radboud University Medical Center Nijmegen, Netherlands, sequentially assigned them seven groups. Eligible healthy, aged 18-55 years, tested negative for...
Plasmodium falciparum malaria remains one of the world's leading causes human suffering and poverty. Each year, disease takes 1–3 million lives, mainly in sub-Saharan Africa. The adhesion infected erythrocytes (IEs) to vascular endothelium or placenta is key event pathogenesis severe P. infection. In pregnant women, parasites express a single unique member erythrocyte membrane protein 1 (PfEMP1) family named VAR2CSA, which associated with ability IEs adhere specifically chondroitin sulphate...
The binding of erythrocytes infected with mature blood stage parasites to the vascular bed is key pathogenesis malignant malaria. mediated by members Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family. PfEMP1s can be divided into groups, and it has previously been suggested that expressing group A or B/A are most pathogenic. To test hypothesis first malaria infections in infants young children dominated PfEMP1s, we measured plasma Ab level against 48 recombinant PfEMP1...
ABSTRACT In areas of endemicity pregnancy-associated malaria is an important cause maternal anemia, stillbirth, and delivery low-birth-weight children. The syndrome precipitated by the accumulation Plasmodium falciparum -infected erythrocytes in placenta, mediated through interaction between a parasite protein expressed on named variant surface antigen 2-chondroitin sulfate A (VAR2CSA) CSA syncytiotrophoblasts. VAR2CSA large polymorphic consisting six Duffy binding-like (DBL), domains with...
Abstract Placental malaria is caused by Plasmodium falciparum–infected erythrocytes that bind to placental tissue. Binding mediated VAR2CSA, a parasite antigen coded the var gene, which interacts with chondroitin sulfate A (CSA). Consequences include maternal anemia and fetal growth retardation. Antibody-mediated immunity acquired during successive pregnancies, but target of VAR2CSA-specific protective antibodies unclear. We assessed in pregnant women analyzed their relationships protection...
Abstract Intermittent preventive treatment during pregnancy with sulfadoxine–pyrimethamine (IPTp-SP) is a key strategy in the control of pregnancy-associated malaria. However, this compromised by widespread drug resistance from single-nucleotide polymorphisms Plasmodium falciparum dihydrofolate reductase and dihydropteroate synthetase genes. During September 2008–October 2010, we monitored cohort 924 pregnant women an area Tanzania declining malaria transmission. P. parasites were genotyped,...
Many tumors express proteoglycans modified with oncofetal chondroitin sulfate glycosaminoglycan chains (ofCS), which are normally restricted to the placenta. However, role of ofCS in cancer is largely unknown. The function was analyzed using recombinant ofCS-binding VAR2CSA protein (rVAR2) derived from malaria parasite, Plasmodium falciparum We demonstrate that plays a key tumor cell motility by affecting canonical integrin signaling pathways. Binding rVAR2 cells inhibited interaction...