A5012109238- Immunotherapy and Immune Responses
- Inhalation and Respiratory Drug Delivery
- Immune Cell Function and Interaction
- SARS-CoV-2 and COVID-19 Research
- Monoclonal and Polyclonal Antibodies Research
- RNA Interference and Gene Delivery
- vaccines and immunoinformatics approaches
- Immune Response and Inflammation
- Air Quality and Health Impacts
- Nanoparticles: synthesis and applications
- Inflammasome and immune disorders
- Immunodeficiency and Autoimmune Disorders
- Advanced Drug Delivery Systems
- COVID-19 Clinical Research Studies
- Viral gastroenteritis research and epidemiology
- Pneumonia and Respiratory Infections
- T-cell and B-cell Immunology
- Nanoparticle-Based Drug Delivery
- Peripheral Neuropathies and Disorders
- Aerosol Filtration and Electrostatic Precipitation
- Toxin Mechanisms and Immunotoxins
- Viral Infections and Immunology Research
- Cancer Immunotherapy and Biomarkers
- Field-Flow Fractionation Techniques
- Animal Virus Infections Studies
University of Bern
2014-2024
Infectious Disease Research Institute
2018-2022
Access to Advanced Health Institute
2022
Fred Hutch Cancer Center
2020-2021
University Hospital of Bern
2013-2017
SARS-CoV-2 is a betacoronavirus virus responsible for the COVID-19 pandemic. Here, we determine X-ray crystal structure of potent neutralizing monoclonal antibody, CV30, isolated from patient infected with SARS-CoV-2, in complex receptor binding domain. The reveals that CV30 binds to an epitope overlaps human ACE2 motif providing structural basis its neutralization. also induces shedding S1 subunit, indicating additional mechanism A germline reversion results substantial reduction both...
SARS-CoV-2 is one of three coronaviruses that have crossed the animal-to-human barrier and caused widespread disease in past two decades. The development a universal human coronavirus vaccine could prevent future pandemics. We characterize 198 antibodies isolated from four COVID-19+ subjects identify 14 neutralizing antibodies. One targets N-terminal domain (NTD), recognizes an epitope S2, 11 bind receptor-binding (RBD). Three anti-RBD cross-neutralize SARS-CoV-1 by effectively blocking...
The respiratory tract is an attractive target organ for novel diagnostic and therapeutic applications with nano-sized carriers, but their immune effects interactions key resident antigen-presenting cells (APCs) such as dendritic (DCs) alveolar macrophages (AMs) in different anatomical compartments remain poorly understood. Polystyrene particles ranging from 20 nm to 1,000 were instilled intranasally BALB/c mice, APC populations airways, lung parenchyma, lung-draining lymph nodes (LDLNs)...
Aluminum salts, developed almost a century ago, remain the most commonly used adjuvant for licensed human vaccines. Compared to more recently vaccine adjuvants, aluminum adjuvants such as Alhydrogel are heterogeneous in nature, consisting of 1-10 micrometer-sized aggregates nanoparticle oxyhydroxide fibers. To determine whether particle size and aggregated state affects its activity, we scalable, top-down process produce stable nanoparticles (nanoalum) from clinical by including poly(acrylic...
Abstract Emerging SARS-CoV-2 variants have raised concerns about resistance to neutralizing antibodies elicited by previous infection or vaccination. We examined whether sera from recovered and naïve donors collected prior to, following immunizations with existing mRNA vaccines, could neutralize the Wuhan-Hu-1 B.1.351 variants. Pre-vaccination neutralized sporadically B.1.351, but a single immunization boosted titers against all SARS-CoV-1 up 1000-fold. Neutralization was due targeting...
ABSTRACT B cells specific for the SARS-CoV-2 S envelope glycoprotein spike were isolated from a COVID-19-infected subject using stabilized spike-derived ectodomain (S2P) twenty-one days post-infection. Forty-four S2P-specific monoclonal antibodies generated, three of which bound to receptor binding domain (RBD). The minimally mutated germline and derived different cell lineages. Only two displayed neutralizing activity against pseudo-virus. most potent antibody RBD in manner that prevented...
Nanosized particles may enable therapeutic modulation of immune responses by targeting dendritic cell (DC) networks in accessible organs such as the lung. To date, however, effects nanoparticles on DC function and downstream remain poorly understood.Bone marrow-derived DCs (BMDCs) were exposed vitro to 20 or 1,000 nm polystyrene (PS) particles. Particle uptake kinetics, surface marker expression, soluble protein antigen degradation, well CD4(+) T-cell proliferation cytokine production...
Abstract The involvement of innate receptors that recognize pathogen- and danger-associated molecular patterns is critical to programming an effective adaptive immune response vaccination. synthetic TLR4 agonist glucopyranosyl lipid adjuvant (GLA) synergizes with the squalene oil-in-water emulsion (SE) formulation induce strong responses. Although signaling through MyD88 TIR domain–containing adapter inducing IFN-β are essential for GLA-SE activity, mechanisms underlying synergistic activity...
Converting a vaccine into thermostable dry powder is advantageous as it reduces the resource burden linked with cold chain and provides flexibility in dosage administration through different routes. Such presentation may be especially useful development of towards respiratory infectious disease tuberculosis (TB). This study assesses immunogenicity protective efficacy spray-dried ID93+GLA-SE, promising TB candidate, against Mycobacterium (Mtb) murine model when administered via Four routes...
Many pathogens establish infection at mucosal surfaces such as the enteric pathogen Enterotoxigenic E. coli (ETEC). Thus, there is a pressing need for effective vaccination strategies that promote protective immunity surfaces. Toll-like receptor (TLR) ligands have been extensively developed vaccine adjuvants to systemic immunity, whereas attenuated bacterial toxins including cholera toxin and heat-labile (LT) initially immunity. Here we evaluate ability of TLR4 agonist second-generation...
Anti-myelin-associated glycoprotein (MAG) neuropathy is a disabling autoimmune peripheral that caused by circulating monoclonal IgM autoantibodies directed against the human natural killer-1 (HNK-1) epitope. This carbohydrate epitope highly expressed on adhesion molecules such as MAG, present in myelinated nerves. We previously showed therapeutic potential of glycopolymer poly(phenyl disodium 3-O-sulfo-β-d-glucopyranuronate)-(1→3)-β-d-galactopyranoside (PPSGG) selectively neutralizing...
An effective HIV-1 vaccine will likely need to elicit broadly neutralizing antibodies (bNAbs). Broad and potent VRC01-class bNAbs have been isolated from multiple infected individuals, suggesting that they could be reproducibly elicited by vaccination. Several envelope-derived germline-targeting immunogens designed engage naive precursor B cells. However, also present off-target epitopes hinder development of bNAbs. We characterize a panel anti-idiotypic monoclonal (ai-mAbs) raised against...
Enterotoxigenic E. coli (ETEC) is a leading cause of moderate-to-severe diarrhoea. ETEC colonizes the intestine through fimbrial tip adhesin colonization factors and produces heat-stable and/or heat-labile (LT) toxins, stimulating fluid electrolyte release to watery We reported that vaccine containing recombinant factor antigen (CfaEB) targeting I (CFA/I) an attenuated LT toxoid (dmLT) elicited mucosal systemic immune responses against both targets. Additionally, toll-like receptor 4 ligand...
Immunogenic agents known as adjuvants play a critical role in many vaccine formulations. Adjuvants often signal through Toll-like receptor (TLR) pathways, including formulations licensed vaccines that target TLR4. While TLR4 is predominantly for responding to lipopolysaccharide (LPS), component of Gram-negative bacterial membranes, it has been shown be number molecular structures, phospholipids. Therefore, phospholipid-based pharmaceutical might have off-target effects by signaling TLR4,...