A5038652387- Malaria Research and Control
- Complement system in diseases
- Mosquito-borne diseases and control
- HIV Research and Treatment
- Research on Leishmaniasis Studies
- Monoclonal and Polyclonal Antibodies Research
- vaccines and immunoinformatics approaches
- Glycosylation and Glycoproteins Research
- Pregnancy and preeclampsia studies
- Hepatitis Viruses Studies and Epidemiology
- Parasites and Host Interactions
- SARS-CoV-2 and COVID-19 Research
- Immunotherapy and Immune Responses
- Drug Transport and Resistance Mechanisms
- RNA Interference and Gene Delivery
- Blood Coagulation and Thrombosis Mechanisms
- Biochemical and Structural Characterization
- Invertebrate Immune Response Mechanisms
- Proteoglycans and glycosaminoglycans research
- Hepatitis B Virus Studies
- Parkinson's Disease Mechanisms and Treatments
- Hepatitis C virus research
- Trypanosoma species research and implications
- Influenza Virus Research Studies
- Viral Infections and Outbreaks Research
University of Copenhagen
2016-2025
Aarhus University Hospital
2024
Copenhagen University Hospital
2013-2023
Rigshospitalet
2012-2022
Herlev Hospital
2019
Institut de Recherche pour le Développement
2015
Noguchi Memorial Institute for Medical Research
2003
London School of Hygiene & Tropical Medicine
2001
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...
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...
Abstract In areas of endemic parasite transmission, protective immunity to Plasmodium falciparum malaria is acquired over several years with numerous disease episodes. Acquisition Abs parasite-encoded variant surface Ags (VSA) on the infected erythrocyte membrane important in development immunity, as disease-causing parasites appear be those not controlled by preexisting VSA-specific Abs. this work we report that VSA expressed from young Ghanaian children P. were commonly and strongly...
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...
Abstract Aggregation of the 140-residue protein α-synuclein (αSN) is a key factor in etiology Parkinson’s disease. Although intensely anionic C-terminal domain (CTD) αSN does not form part amyloid core region or affect membrane binding ability, truncation reduction charges CTD promotes fibrillation through as yet unknown mechanisms. Here, we study stepwise truncated CTDs and identify threshold around residue 121; constructs shorter than this dramatically increase their tendency. Remarkably,...
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...
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...
The Plasmodium falciparum Pfs230 and Pfs48/45 proteins are expressed during transmission from man to mosquito leading candidates for a malaria blocking vaccine. Individually they generate (TB) antibodies in rodent models. Whether the single protein vaccines suitable use field settings will primarily depend on their potency elicit functional antibodies. We hypothesized that combination of both be more potent than each individually. Therefore we designed chimeric composed fragments as well...
Abstract Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family members mediate receptor- and tissue-specific sequestration of infected erythrocytes (IEs) in malaria. Antibody responses are a central component naturally acquired malaria immunity. PfEMP1-specific IgG likely protects by inhibiting IE through IgG-Fc Receptor (FcγR) mediated phagocytosis killing antibody-opsonized IEs. The affinity afucosylated to FcγRIIIa is up 40-fold higher than fucosylated IgG, resulting...
Summary Pregnancy‐associated malaria (PAM) is caused by Plasmodium falciparum ‐infected erythrocytes (IEs) that bind to chondroitin sulphate A (CSA) in the placenta PAM‐associated clonally variant surface antigens (VSA). Pregnancy‐specific VSA (VSA PAM ), which include PfEMP1 VAR2CSA, are targets of IgG‐mediated protective immunity PAM. Here, we report an investigation specificity naturally acquired PAM, using eight human monoclonal IgG1 antibodies react exclusively with intact CSA‐adhering...
Pregnancy-associated malaria is a major health problem, which mainly affects primigravidae living in endemic areas. The syndrome precipitated by accumulation of infected erythrocytes placental tissue through an interaction between chondroitin sulphate A on syncytiotrophoblasts and parasite-encoded protein the surface erythrocytes, believed to be VAR2CSA. VAR2CSA polymorphic approximately 3,000 amino acids forming six Duffy-binding-like (DBL) domains. For vaccine development it important...
Malaria, caused by the parasite Plasmodium falciparum, is responsible for substantial morbidity, mortality and economic losses in tropical regions of world. Pregnant women are exceptionally vulnerable to severe consequences infection, due specific adhesion parasite-infected erythrocytes placenta. This mediated a unique variant PfEMP1, encoded, hyper-variable antigen placed on surface infected cells. variant, called VAR2CSA, binds chondroitin sulfate A syncytiotrophoblasts intervillous space...
Pregnancy-associated malaria is caused by Plasmodium falciparum parasites binding specifically to chondroitin sulfate A in the placenta. This sequestration of a major cause low birth weight infants and anemia mothers. VAR2CSA, polymorphic multi-domain protein PfEMP1 family, main parasite ligand for CSA binding, identification protective antibody epitopes essential VAR2CSA vaccine development. Attempts determine crystallographic structures or its domains have not been successful yet. In this...
Binding to chondroitin sulfate A by VAR2CSA, a parasite protein expressed on infected erythrocytes, allows placental sequestration of Plasmodium falciparum-infected erythrocytes. This leads severe consequences such as maternal anemia, stillbirths, and intrauterine growth retardation. The latter has been clearly associated increased morbidity mortality the infants. Acquired anti-VAR2CSA antibodies have with improved pregnancy outcomes, suggesting vaccine could prevent syndrome. However,...