A5084030314- Malaria Research and Control
- Mosquito-borne diseases and control
- Liver Disease Diagnosis and Treatment
- Hepatitis Viruses Studies and Epidemiology
- Liver Disease and Transplantation
- Parasites and Host Interactions
- Alzheimer's disease research and treatments
- Drug Transport and Resistance Mechanisms
- Liver physiology and pathology
- Endoplasmic Reticulum Stress and Disease
- Hepatitis B Virus Studies
- Viral gastroenteritis research and epidemiology
- Hepatitis C virus research
- HIV Research and Treatment
- Invertebrate Immune Response Mechanisms
- Diet and metabolism studies
- Neuroscience and Neuropharmacology Research
- Liver Diseases and Immunity
- Complement system in diseases
- Per- and polyfluoroalkyl substances research
- Drug-Induced Hepatotoxicity and Protection
- Peroxisome Proliferator-Activated Receptors
- Lipid metabolism and biosynthesis
- Cholesterol and Lipid Metabolism
- Birth, Development, and Health
Yecuris (United States)
2020-2024
Infectious Disease Research Institute
2017-2018
Center for Infectious Disease Research
2017-2018
Ghent University Hospital
2013-2018
Ghent University
2013-2017
Laboratoire National de Référence
2011
Malaria, which is the result of Plasmodium falciparum infection, a global health threat that resulted in 655,000 deaths and 216 million clinical cases 2010 alone. Recent phase 3 trials with malaria vaccine candidate RTS,S/AS01 (RTS,S) children has demonstrated modest efficacy against severe malaria. RTS,S targets pre-erythrocytic disease induces high antibody titers P. circumsporozoite protein (CSP) moderate CD4(+) T cell response. The individual contribution these adaptive immune responses...
Highlights•Human PfRH5 vaccination induces cross-reactive neutralizing antimalarial antibodies•Neutralizing human antibodies bind epitopes close to the basigin binding site•Some non-neutralizing potentiate those several malaria proteins•Potentiating slow erythrocyte invasion by a new epitope on PfRH5SummaryThe Plasmodium falciparum reticulocyte-binding protein homolog 5 (PfRH5) is leading target for next-generation vaccines against disease-causing blood-stage of malaria. However, little...
<h3>Objective</h3> The hepatitis E virus (HEV) is responsible for approximately 20 million infections per year worldwide. Although most infected people can spontaneously clear an HEV infection, immune-compromised individuals may evolve towards chronicity. Chronic infection be cured using ribavirin, but viral isolates with low ribavirin sensitivity have recently been identified. some cultured <i>in vitro, in vivo</i> studies are essentially limited to primates and pigs. Since the use of these...
(See the editorial commentary by Hodskog and Albert, on pages 163–5.) Background. The prevalence correlates of CXCR4-use in recently diagnosed patients impact X4/DM transmission remain largely unknown. Method. Genotypic coreceptor use determination baseline sample 539 individuals. Correlation with clinical, viral epidemiological data information events as obtained through phylogenetic analysis protease reverse transcriptase sequences. Results. was predicted 12 to 19% patients, depending...
Long-lasting and sterile protective immunity against Plasmodium falciparum can be achieved by immunization of malaria-naive human volunteers under chloroquine prophylaxis with sporozoites delivered mosquito bites (CPS-immunization). Protection is mediated sporozoite/liver-stage immunity. In this study, the capacity CPS-induced antibodies to interfere sporozoite functionality development was explored. IgG purified from plasma samples obtained before after CPS-immunization two separate...
A highly efficacious pre-erythrocytic stage vaccine would be an important tool for the control and elimination of malaria but is currently unavailable. High-level protection in humans can achieved by experimental immunization with Plasmodium falciparum sporozoites attenuated radiation or under anti-malarial drug coverage. Immunization genetically parasites (GAP) attractive alternative approach. In this study, we present data on safety protective efficacy using deletions two genes, that newly...
Abstract Liver-generated plasma apolipoprotein E (apoE) does not enter the brain but nonetheless correlates with Alzheimer’s disease (AD) risk and AD biomarker levels. Carriers of APOE ε4, strongest genetic factor, exhibit lower apoE altered integrity already at mid-life versus non- ε4 carriers. Whether liver-derived or specifically an liver phenotype promotes neurodegeneration is unknown. Here we investigated brains Fah−/− , Rag2−/−, Il2rg−/− mice on Non-Obese Diabetic (NOD) background...
The invention of liver-humanized mouse models has made it possible to directly study the pre-erythrocytic stages Plasmodium falciparum. In contrast, current blood stage infection in vivo are extremely limited. Humanization stream is achievable by frequent injections human red cells (hRBCs) and currently only system with which malaria infections a small animal model. Infections have been primarily achieved direct injection P. falciparum-infected RBCs but as such, this modality does not model...
Abstract Whole-sporozoite (WSp) malaria vaccines induce protective immune responses in animal models and humans. A recent clinical trial with a WSp vaccine comprising genetically attenuated parasites (GAP) which arrest growth early the liver (PfSPZ-GA1), showed that GAPs can be safely administered to humans immunogenicity is comparable radiation-attenuated PfSPZ Vaccine. late stage (LA-GAP) have potential for increased potency as shown rodent models. Here we describe generation of four...
Advanced non-alcoholic fatty liver disease (NAFLD) is a rapidly emerging global health problem associated with pre-disposing genetic polymorphisms, most strikingly an isoleucine to methionine substitution in patatin-like phospholipase domain-containing protein 3 (PNPLA3-I148M). Here, we study how human hepatocytes PNPLA3 148I and 148M variants engrafted the livers of broadly immunodeficient chimeric mice respond hypercaloric diets. As early as four weeks, developed dyslipidemia, impaired...
A malaria vaccine that prevents infection will be an important new tool in continued efforts of elimination, and such vaccines are under intense development for the major human parasite Plasmodium falciparum (Pf). Antibodies elicited by can block initial phases when sporozoites deposited into skin mosquito bite then target liver further development. However, there currently no standardized vivo preclinical models measure inhibitory activity antibody specificities against Pf sporozoite via...
Aminoquinolines and piperazines, linked or not, have been used successfully to treat malaria, some molecules of this family also exhibit antiviral properties. Here we tested several derivatives 4-aminoquinolines piperazines for their activity against hepatitis C virus (HCV). We screened 11 from three different families compounds, identified anti-HCV in cell culture six them. Of these, selected a compound (B5) that is currently ending clinical phase I evaluation neurodegenerative diseases. In...
There is a pressing need for safe and highly effective Plasmodium falciparum (Pf) malaria vaccines. The circumsporozoite protein (CS), expressed on sporozoites during early hepatic stages, leading target vaccine candidate, but clinical efficacy has been modest so far. Conversely, whole-sporozoite (WSp) vaccines have consistently shown high levels of sterilizing immunity constitute promising approach to immunization against malaria. Here, we describe novel WSp that employs transgenic rodent...
Significance Fatal cases of yellow fever are preceded by the development hemorrhagic complications. While virus is known to infect hepatocytes, relationship between hepatocyte infection and hemorrhage currently undefined. Here, we identified high concentrations D-dimer in blood patients, indicative a process that involves activation consumption clotting factors. We then developed mouse model which only transplanted human hepatocytes could be infected at levels. By examining parameters this...
Abstract Objectives Plasmodium falciparum sporozoites, deposited in the skin by infected Anopheles mosquitoes taking a blood meal, cross endothelium of capillaries and travel to liver where they traverse Kupffer cells hepatocytes finally invade small number latter. In hepatocytes, sporozoites replicate, differentiate give rise large numbers merozoites that are released into bloodstream red cells, thus initiating symptomatic stage. Using vitro systems rodent models, it has been shown...
Malaria eradication necessitates new tools to fight the evolving and complex Plasmodium pathogens. These include prophylactic drugs that eliminate liver stages consequently prevent clinical disease, decrease transmission, reduce propensity for resistance development. Currently, identification of these relies on in vitro P. falciparum stage assays or vivo causal prophylaxis using rodent malaria parasites; there is no method directly test activity candidate antimalarials against human...
Chimeric mice with humanized livers represent a promising tool for infections Plasmodium falciparum to evaluate novel methods prevention and treatment of pre-erythrocytic stages. Adequate assessment hepatic is generally compromised by the limited number human hepatocytes infected developing parasites. A qPCR-based method has been developed that sensitively reliably detects P. liver stage infection quantitatively expresses results as parasites per hepatocyte. This assay allows detection after...
ABSTRACT Hepatitis C virus (HCV) species tropism is incompletely understood. We have previously shown that at the level of entry, human CD81 and occludin (OCLN) comprise minimal set factors needed for viral uptake into murine cells. As an alternative approach to genetic humanization, barriers can be overcome by adapting HCV use orthologues these entry factors. generated a tropic (mtHCV or Jc1/mCD81) strain harboring three mutations within envelope proteins allowed productive mouse cell...
Abstract Plasma apolipoprotein E levels were previously associated with the risk of developing Alzheimer’s disease (AD), cerebrospinal fluid AD biomarkers, cognition and imaging brain measures. Outside brain, liver is primary source apoE transplantation studies have demonstrated that liver-derived does not cross blood–brain-barrier. How hepatic may be implicated in behavioral cognitive performance clear. In current study, we behaviorally tested FRGN mice humanized harboring ε3/ε3 genotype...
Natural killer (NK) cells have different roles in the host response against Plasmodium-induced malaria depending on stage of infection. Liver NK a protective role during initial hepatic infection by production TH1-type cytokines IFN-γ and TNF-α. In subsequent erythrocytic infection, also induce protection through Th1-type but, addition, may promote development cerebral via CXCR3-induction CD8+ T resulting migration these to brain. We recently shown that regulatory Ly49E receptor is expressed...
Abstract Background Per- and polyfluoroalkyl substances (PFAS) are persistent organic pollutants with myriad adverse effects. While perfluorooctanoic acid (PFOA) perfluorooctane sulfonic (PFOS) the most common contaminants, levels of replacement PFAS, such as perfluoro-2-methyl-3-oxahexanoic (GenX), increasing. In rodents, PFOA, PFOS, GenX have several effects on liver, including nonalcoholic fatty liver disease. Objective We aimed to determine human-relevant mechanisms PFAS induced hepatic...