A5065566618- Monoclonal and Polyclonal Antibodies Research
- SARS-CoV-2 and COVID-19 Research
- Parkinson's Disease Mechanisms and Treatments
- Virology and Viral Diseases
- SARS-CoV-2 detection and testing
- Aquaculture disease management and microbiota
- Biochemical and Structural Characterization
- Bacteriophages and microbial interactions
- Cellular transport and secretion
- Cancer Cells and Metastasis
- Genetic Neurodegenerative Diseases
- Multiple Myeloma Research and Treatments
- Food Allergy and Anaphylaxis Research
- Botulinum Toxin and Related Neurological Disorders
- Hepatitis C virus research
- Glioma Diagnosis and Treatment
- Viral Infections and Outbreaks Research
- Ubiquitin and proteasome pathways
- Transgenic Plants and Applications
- Atherosclerosis and Cardiovascular Diseases
- Aquaculture Nutrition and Growth
- Vaccine Coverage and Hesitancy
- Hepatitis B Virus Studies
- Galectins and Cancer Biology
- Microbial infections and disease research
University of Copenhagen
2019-2024
Copenhagen University Hospital
2019-2021
Rigshospitalet
2021
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...
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...
Diffuse gliomas are the most common primary malignant brain tumor. Although extracranial metastases rarely observed, recent studies have shown presence of circulating tumor cells (CTCs) in blood glioma patients, confirming that a subset capable entering circulation. The isolation and characterization CTCs could provide non-invasive method for repeated analysis mutational phenotypic state during course disease. However, efficient detection has proven to be challenging due lack consistently...
HER2-targeted therapies have revolutionized the treatment of HER2-positive breast cancer patients, leading to significant improvements in tumor response rates and survival. However, resistance incomplete remain considerable challenges. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition is a novel therapeutic strategy for management dyslipidemia by enhancing clearance low-density lipoprotein cholesterol receptors, however recent evidence also shows links between PCSK9 cells. We...
Administration of PCSK9-specific monoclonal antibodies, as well peptide-based PCSK9 vaccines, can lower plasma LDL cholesterol by blocking PCSK9. However, these treatments also cause an increase in levels, presumably due to the formation immune complexes. Here, we utilize a versatile capsid virus-like particle (cVLP)-based vaccine platform deliver both full-length (FL) and PCSK9-derived peptide antigens, investigate whether induction broader polyclonal anti-PCSK9 antibody response would...
Abstract α-Synuclein (α-syn) accumulates as insoluble amyloid but also forms soluble α-syn oligomers (αSOs), thought to be even more cytotoxic than fibrils. To detect and block the unwanted activities of these αSOs, we have raised 30 monoclonal antibodies (mAbs) against different ranging from unmodified αSOs species stabilized by lipid peroxidation products polyphenols, formed C-terminally truncated α-syn, multivalent display on capsid virus-like particles (cVLPs). While mAbs generally show...
Capsid virus-like particles (cVLPs) are used as molecular scaffolds to increase the immunogenicity of displayed antigens. Modular platforms have been developed whereby antigens attached surface pre-assembled cVLPs. However, it remains unknown what extent employed cVLP backbone and conjugation system may influence immune response elicited against antigen. Here, we performed a head-to-head comparison antigen-specific IgG responses by modular cVLP-vaccines differing their or system,...
The Gram-negative bacterium A. salmonicida is the causal agent of furunculosis and used to be one most loss-causing bacterial infections in salmonid aquaculture industry with a mortality rate about 90% until 1990s, when an inactivated vaccine mineral oil as adjuvant was successfully implemented control disease. However, use this associated inflammatory side effects peritoneal cavity well autoimmune reactions Atlantic salmon, incomplete protection has been reported rainbow trout. We here...
Abstract The rapid development of a SARS-CoV-2 vaccine is global priority. Here, we developed two capsid-like particle (CLP)-based vaccines displaying the receptor-binding domain (RBD) spike protein. RBD antigens were displayed on AP205 CLPs through novel split-protein Tag/Catcher ensuring unidirectional and high-density display RBD. Both soluble recombinant RBD, bound ACE2 receptor with nanomolar affinity. Mice vaccinated or CLP-displayed formulated in Squalene-Water-Emulsion. RBD-CLP...
Hypersensitivity to a contact allergen is one of the most abundant forms inflammatory skin disease. Today, more than 20% general population are sensitized or allergens, making this disease an important healthcare issue, as re-exposure can initiate clinical termed allergic dermatitis (ACD). The current standard treatment using corticosteroids effective, but it has side effects when used for longer periods. Therefore, there need new alternative therapies severe ACD. In study, we versatile...
Yearly, about 1.5 million people become chronically infected with hepatitis C virus (HCV) and for the 71 chronic HCV infection 400,000 die from related morbidities, including liver cirrhosis cancer. Effective treatments exist, but challenges cost-of-treatment wide-spread undiagnosed infection, necessitates development of vaccines. Vaccines should induce neutralizing antibodies (NAbs) against envelope (E) transmembrane glycoprotein 2, E2, which partly depends on its interaction partner, E1,...
<title>Abstract</title> Aggregation of α-synuclein (α-syn) is critical to the development synucleinopathies such as Parkinson’s Disease (PD), yet we do not have any effective therapy against these diseases. α-syn accumulates insoluble amyloid in intracellular Lewy Bodies (LBs) but also forms soluble αSOs (αSOs) which are thought be even more cytotoxic than fibrils. We lack tools detect and block unwanted activities αSOs. To address this, raised monoclonal antibodies (mAbs) different αSOs,...