A5083273777- SARS-CoV-2 and COVID-19 Research
- Immunotherapy and Immune Responses
- Immune Cell Function and Interaction
- CAR-T cell therapy research
- Cancer Immunotherapy and Biomarkers
- COVID-19 Clinical Research Studies
- SARS-CoV-2 detection and testing
- Exercise and Physiological Responses
- Monoclonal and Polyclonal Antibodies Research
- Mosquito-borne diseases and control
- Genomics, phytochemicals, and oxidative stress
- Cancer Research and Treatments
- interferon and immune responses
- Virus-based gene therapy research
- Immune cells in cancer
- Bacteriophages and microbial interactions
- Viral Infections and Vectors
- Long-Term Effects of COVID-19
- Cell death mechanisms and regulation
- Plant Virus Research Studies
- Eicosanoids and Hypertension Pharmacology
- Inflammasome and immune disorders
- T-cell and B-cell Immunology
- Synthesis and biological activity
- Tissue Engineering and Regenerative Medicine
Aarhus University
2020-2024
Copenhagen University Hospital
2012-2023
University of Copenhagen
2018-2023
Hvidovre Hospital
2023
ExpreS2ion Biotechnologies (Denmark)
2023
Herlev Hospital
2013-2021
Gentofte Hospital
2018
Society for Immunotherapy of Cancer
2014
Abstract Antiviral strategies to inhibit Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) and the pathogenic consequences of COVID-19 are urgently required. Here, we demonstrate that NRF2 antioxidant gene expression pathway is suppressed in biopsies obtained from patients. Further, uncover agonists 4-octyl-itaconate (4-OI) clinically approved dimethyl fumarate (DMF) induce a cellular antiviral program potently inhibits replication SARS-CoV2 across cell lines. The inhibitory effect...
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...
Understanding the molecular pathways driving acute antiviral and inflammatory response to SARS-CoV-2 infection is critical for developing treatments severe COVID-19. Here, we find decreasing number of circulating plasmacytoid dendritic cells (pDCs) in COVID-19 patients early after symptom onset, correlating with disease severity. pDC depletion transient coincides decreased expression type I IFNα systemic cytokines CXCL10 IL-6. Using an vitro stem cell-based human model, further demonstrate...
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has created an urgent need for new technologies to treat COVID-19. Here we report a 2'-fluoro protected RNA aptamer that binds with high affinity the receptor binding domain (RBD) of SARS-CoV-2 spike protein, thereby preventing its interaction host ACE2. A trimerized version matching three RBDs in each complex enhances down low picomolar range. Binding mode and specificity aptamer-spike is supported by biolayer...
ZBP1 is an interferon-induced cytosolic nucleic acid sensor that facilitates antiviral responses via RIPK3. Although ZBP1-mediated programmed cell death widely described, whether and how it promotes inflammatory signaling unclear. Here, we report a ZBP1-induced pathway mediated by K63- M1-linked ubiquitin chains, which depends on RIPK1 RIPK3 as scaffolds independently of death. In human HT29 cells, associated with well ligases cIAP1 LUBAC. ubiquitination to promote TAK1- IKK-mediated...
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...
Adoptive cell therapy (ACT) using in vitro expanded tumor infiltrating T lymphocytes (TILs) from biopsy material represents a highly promising treatment of disseminated cancer. A crucial prerequisite for successful ACT is sufficient recruitment transferred to the site; however, despite infusion billions lymphocytes, infiltration into post limited. By PCR and Luminex analyses we found that majority malignant melanoma (MM) lines expressed chemokines CXCL1/Groα, CXCL8/IL-8, CXCL12/SDF-1 CCL2....
Abstract Tools to monitor SARS-CoV-2 transmission and immune responses are needed. We present a neutralization ELISA determine the levels of Ab-mediated virus preclinical model focused immunization strategy. The is strongly correlated with elaborate plaque reduction test (ρ = 0.9231, p < 0.0001). potency convalescent sera correlates IgG titers against receptor-binding domain (RBD) spike 0.8291 0.8297, respectively; 0.0001) lesser extent protein N 0.6471, vaccine NMRI mice models using...
The alpha/B.1.1.7 SARS-CoV-2 lineage emerged in autumn 2020 the United Kingdom and transmitted rapidly until winter 2021 when it was responsible for most new COVID-19 cases many European countries. incidence domination likely due to a fitness advantage that could be driven by receptor-binding domain (RBD) residue change (N501Y), which also independently other variants of concern such as beta/B.1.351 gamma/P.1 strains. Here, we present functional characterization variant show an eightfold...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a worldwide pandemic. Here, we present non-human primate immunogenicity and protective efficacy data generated with the capsid virus-like particle (cVLP)-based vaccine ABNCoV2 that previously demonstrated in mice. In rhesus macaques, single vaccination either 15 or 100 μg induced binding neutralizing antibodies dose-dependent manner, at levels comparable to those measured human convalescents. A second administration led...
Abstract Cancer immunotherapy can result in durable tumor regressions some patients. However, patients who initially respond often experience progression. Here, we report mechanistic evidence of tumoral immune escape an exemplary clinical case: a patient with metastatic melanoma developed disease recurrence following initial, unequivocal radiologic complete regression after T-cell–based immunotherapy. Functional cytotoxic T-cell responses, including responses to one mutant neoantigen, were...
The human Vγ9Vδ2 T cell is a unique type that holds great potential in immunotherapy of cancer. In particular, the therapeutic this adoptive therapy (ACT) has gained interest. regard optimization vitro expansion methods and functional characterization desirable. We show cells, expanded with zoledronic acid (Zometa or ZOL) Interleukin-2 (IL-2), are efficient cancer killers trend towards increased killing efficacy after prolonged time. Thus, cells for 25 days killed prostate more efficiently...
The patterns of humoral and cellular responses to SARS-CoV-2 were studied in Swedish primary health care workers (n = 156) for 6 months during the Covid-19 pandemic. Serum IgA IgG SARS-CoV-2, T-cell proliferation cytokine secretion, demographic clinical data, PCR-verified infection, self-reported symptoms monitored. multivariate method OPLS-DA was used identify immune response coupled protection from Covid-19. Contracting associated with SARS-CoV-2-specific neutralizing serum IgG, T cell,...
Chemokines are essential mediators of cellular trafficking, interactions and tumor development. Though adoptive cell therapy (ACT) has been a tremendous success in the treatment metastatic melanoma (MM), major obstacle for successful ACT, is limited homing effector T cells to immune suppressive sites. We hypothesized that equipping with chemokine receptors matching chemokines microenvironment, could improve cells. from malignant ascites (n = 13); blood ovarian cancer (OC) patients 14);...
The antimicrobial medication malarone (atovaquone/proguanil) is used as a fixed-dose combination for treating children and adults with uncomplicated malaria or chemoprophylaxis preventing in travelers. It an inexpensive, efficacious, safe drug frequently prescribed around the world. Following anecdotal evidence from 17 patients provinces of Quebec Ontario, Canada, suggesting that malarone/atovaquone may present some benefits protecting against COVID-19, we sought to examine its antiviral...