A5015106480- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- Hepatitis B Virus Studies
- RNA Interference and Gene Delivery
- Immune cells in cancer
- Hepatitis Viruses Studies and Epidemiology
- Immunodeficiency and Autoimmune Disorders
- Hepatitis C virus research
- Viral Infections and Outbreaks Research
- Cancer Immunotherapy and Biomarkers
- Reproductive System and Pregnancy
- MicroRNA in disease regulation
- Diabetes and associated disorders
- Regulation of Appetite and Obesity
- Biochemical Analysis and Sensing Techniques
- Immune Response and Inflammation
- Cytokine Signaling Pathways and Interactions
- Human Health and Disease
- Single-cell and spatial transcriptomics
- Adipokines, Inflammation, and Metabolic Diseases
- Congenital gastrointestinal and neural anomalies
Janssen (Belgium)
2023-2024
Johnson & Johnson (Israel)
2023
Babraham Institute
2017-2021
KU Leuven
2010-2013
Vlaams Instituut voor Biotechnologie
2011
VIB-KU Leuven Center for Microbiology
2011
Germinal center (GC) responses are controlled by T follicular helper (Tfh) and regulatory (Tfr) cells crucial for the generation of high-affinity antibodies. Although biology human circulating tissue Tfh has been established, relationship between blood Tfr defined as CXCR5+Foxp3+ remains elusive. We found that increased in Sjögren syndrome, an autoimmune disease with ongoing GC reactions, especially patients high autoantibody titers, well healthy individuals upon influenza vaccination....
The generation of protective humoral immunity after vaccination relies on the productive interaction between antigen-specific B cells and T follicular helper (Tfh) cells. Despite central role Tfh in vaccine responses, there is currently no validated way to enhance their differentiation humans. From paired human lymph node blood samples, we identify a population circulating that are transcriptionally clonally similar germinal center In clinical trial formulations, were expanded Tanzanian...
The germinal center (GC) response is critical for generating high-affinity humoral immunity and immunological memory, which forms the basis of successful immunization. Control GC thought to require follicular regulatory T (Tfr) cells, a subset suppressive Foxp3+ cells located within GCs. Relatively little known about exact role Tfr how they exert their function. A unique feature reported CXCR5-dependent localization GC. Here, we show that lack CXCR5 on results in reduced frequency, but not...
Abstract Follicular helper T (T FH ) cells control antibody responses by supporting affinity maturation and memory formation. Inadequate function has been found in individuals with ineffective to vaccines, but the mechanism underlying regulation vaccination is not understood. Here, we report that lower serum levels of metabolic hormone leptin associate reduced vaccine influenza or hepatitis B virus vaccines healthy populations. Leptin promotes mouse human differentiation IL-21 production via...
Chronic infection with hepatitis B virus (HBV) develops in millions of patients per year, despite the availability effective prophylactic vaccines. Patients who resolve acute HBV develop HBV-specific polyfunctional T cells accompanied by neutralizing antibodies, while chronic (CHB), immune are dysfunctional and impaired. We describe a lipid nanoparticle (LNP)-formulated mRNA vaccine, optimized for expression core, polymerase, surface (preS2-S) antigens aim inducing an response CHB. Prime...
Background and Aims: Treatment with siRNAs that target HBV has demonstrated robust declines in antigens. This effect is also observed the AAV-HBV mouse model, which was used to investigate if two cycles of GalNAc-HBV-siRNA treatment could induce deeper HBsAg levels or prevent rebound, provide insights into liver immune microenvironment. Methods: C57Bl/6 mice were transduced one different titers for 28 days, resulting stable about 103 105 IU/mL. Mice treated 12 weeks (four doses q3wk) per...
Summary Loss of ζ ‐associated protein 70 (Zap70) results in severe immunodeficiency humans and mice because the critical role Zap70 T‐cell receptor ( TCR ) signalling. Here we describe a novel mouse strain generated by N ‐ethyl‐ ‐nitrosourea mutagenesis, with reduced stability rps mutation . The A243V resulted decreased duration ‐induced calcium responses, equivalent to that induced 50% decrease catalytically active Zap70. reduction signalling through was insufficient substantially perturb...
Suppression of HBV DNA, inhibition surface (HBsAg) production and therapeutic vaccination to reverse HBV-specific T-cell exhaustion in chronic patients are likely required achieve a functional cure. In the AAV-HBV mouse model, can be effective clearing when HBsAg levels low. Using single-cell approach, we investigated liver immune environment with different sustained loss through treatment GalNAc-HBV-siRNA followed by vaccination.AAV-HBV-transduced C57BL/6 mice were treated lower then...
Research on liver-related conditions requires a robust and efficient method to purify viable hepatocytes, lymphocytes all other liver resident cells, such as Kupffer or sinusoidal endothelial cells. Here we describe novel purification using enzymatic digestion, followed by downstream optimized purification. Using this digestion protocol, the cells well hepatocytes could be captured, compared classical mechanical disruption method. Moreover, single-cell RNA-sequencing demonstrated higher...
Abstract Background & Aims Suppression of HBV DNA, inhibition HBsAg production and therapeutic vaccination to reverse HBV-specific T-cell exhaustion in chronic patients are likely required achieve functional cure. In the AAV-HBV mouse model, can be effective clearing when hepatitis B surface (HBsAg) levels low. The factor(s) for mounting an immune control infection unclear. Using a single-cell approach, we investigated liver environment context different as well upon sustained loss...
Abstract Background and Aims Unresolved hepatitis B virus (HBV) infection leads to a progressive state of immune exhaustion that impairs resolution infection, leading chronic (CHB). The immune-competent AAV-HBV mouse is common HBV preclinical competent model, though comprehensive characterization the liver microenvironment its translatability human still lacking. We investigated intrahepatic profile model at single-cell level compared with data from CHB patients in tolerant (IT) active (IA)...
Background Chronic hepatitis B (CHB) is responsible for major disease burden worldwide. However, the number of available therapies limited; cure remains an elusive goal. JNJ-64794964 (JNJ-4964) oral toll-like receptor-7 (TLR7) agonist being evaluated treatment CHB. Here, we investigated capacity JNJ-4964 to induce transcriptomic and immune cell changes in peripheral blood healthy volunteers. Methods Peripheral was collected first-in-human phase 1 trial at multiple time points assess...