A5066849540- Neonatal Respiratory Health Research
- Respiratory viral infections research
- SARS-CoV-2 and COVID-19 Research
- Congenital Diaphragmatic Hernia Studies
- Mosquito-borne diseases and control
- Viral gastroenteritis research and epidemiology
- COVID-19 Impact on Reproduction
- Monoclonal and Polyclonal Antibodies Research
- Reproductive System and Pregnancy
- Pregnancy and preeclampsia studies
- COVID-19 Clinical Research Studies
- SARS-CoV-2 detection and testing
- Bacillus and Francisella bacterial research
- Animal Virus Infections Studies
- Influenza Virus Research Studies
- Endoplasmic Reticulum Stress and Disease
- Mesenchymal stem cell research
- Tracheal and airway disorders
- Virus-based gene therapy research
- Vaccine Coverage and Hesitancy
- Food Allergy and Anaphylaxis Research
- Virology and Viral Diseases
- RNA Interference and Gene Delivery
- Renal and related cancers
- Biotin and Related Studies
University of Bern
1994-2025
Federal Department of Home Affairs
2020-2024
Institute of Virology of the Slovak Academy of Sciences
2023-2024
Innsbruck Medical University
2008
Abstract Variant of concern (VOC) Omicron-BA.1 has achieved global predominance in early 2022. Therefore, surveillance and comprehensive characterization advanced primary cell culture systems animal models are urgently needed. Here, we characterize recombinant spike gene mutants comparison with VOC Delta well-differentiated human nasal bronchial epithelial cells vitro, followed by vivo fitness hamsters, ferrets hACE2-expressing mice, immunized hACE2-mice. We demonstrate a spike-mediated...
The ongoing SARS-CoV-2 pandemic continues to lead high morbidity and mortality. During pregnancy, severe maternal neonatal outcomes placental pathological changes have been described. We evaluate infection at the maternal-fetal interface using precision-cut slices (PCSs) of human placenta. Remarkably, exposure placenta PCSs leads a full replication cycle with infectious virus release. Moreover, susceptibility tissue relates expression levels ACE2. Viral proteins and/or viral RNA are detected...
Approved vaccines are effective against severe COVID-19, but broader immunity is needed new variants and transmission. Therefore, we developed genome-modified live-attenuated (LAV) by recoding the SARS-CoV-2 genome, including 'one-to-stop' (OTS) codons, disabling Nsp1 translational repression removing ORF6, 7ab 8 to boost host immune responses, as well spike polybasic cleavage site optimize safety profile. The resulting OTS-modified LAVs, designated OTS-206 OTS-228, genetically stable can be...
The coronavirus disease 2019 (COVID-19) outbreak revealed the susceptibility of elderly patients to respiratory virus infections, showing cell senescence or subclinical persistent inflammatory profiles and favoring development severe pneumonia. In our study, we evaluated potential influence lung aging on efficiency replication influenza A (IAV) acute syndrome 2 (SARS-CoV-2), as well determining pro-inflammatory antiviral responses distal tissue. Using precision-cut slices (PCLS) from donors...
In vitro systems of primary cystic fibrosis (CF) airway epithelial cells are an important tool to study molecular and functional features the native respiratory epithelium. However, undifferentiated CF cell cultures grown under submerged conditions do not appropriately represent physiological situation. A more advanced culture system based on at air-liquid interface (ALI) recapitulates most in vivo-like properties but requires use invasive sampling methods. this study, we describe a detailed...
Flaviviruses replicate in a wide variety of species and have broad cellular tropism. They are isolated from various body fluids Zika virus (ZIKV), Japanese encephalitis (JEV) West Nile (WNV) RNAs been detected nasopharyngeal swabs. Consequently, we evaluated the tropism host responses upon ZIKV, JEV, WNV, Usutu (USUV) infection using relevant model human upper respiratory tract epithelium based on primary nasal epithelial cells (NECs) cultured at air-liquid interface. NECs were susceptible...
Our understanding of mesenchymal cell subsets and their function in human lung affected by aging certain disease settings remains poorly described. We use a combination flow cytometry, prospective cell-sorting strategies, confocal imaging, modeling microvessel formation using advanced microfluidic chip technology to characterize subtypes postnatal adult lung. Tissue was obtained from patients undergoing elective surgery for congenital pulmonary airway malformations (CPAM) other abnormalities...
The human respiratory syncytial virus (RSV) is a major cause of severe lower tract infections in infants, possibly due to the properties immature neonatal pulmonary immune system. Using newborn lamb, classical model lung development and translational RSV infection, we aimed explore role cell-mediated immunity disease during early life. Remarkably, healthy conditions, developing T cell compartment showed differences that seen mature adult lung. most striking observation being high baseline...
Binding antibodies (BAB) against interferon-beta (IFNbeta) are often determined as screening assays before performing an expensive and elaborate neutralizing antibody (NAB) test.In this study, we compared four BAB tests, a western blot (WB), direct binding enzyme-linked immunosorbent assay (ELISA) (dELISA), capture ELISA (cELISA), commercial enzyme immuno-assay (EIA) in 325 multiple sclerosis patients with without to evaluate the sensitivity specificity detect NAB by receiver operating...
Lung-resident (LR) mesenchymal stem and stromal cells (MSCs) are key elements of the alveolar niche fundamental regulators homeostasis regeneration. We interrogated their function during virus-induced lung injury using highly prevalent respiratory syncytial virus (RSV) which causes severe outcomes in infants. applied complementary approaches with primary pediatric LR-MSCs a state-of-the-art model human RSV infection lamb. Remarkably, RSV-infection led to robust activation, characterized by...
Abstract Variant of concern (VOC) Omicron-BA1 has achieved global predominance in early 2022. Therefore, surveillance and comprehensive characterization Omicron-BA.1 advanced primary cell culture systems multiple animal models is urgently needed. Here, we characterized recombinant spike gene mutants comparison with VOC Delta well-differentiated human nasal bronchial epithelial cells vitro, followed by vivo fitness naïve hamsters, ferrets hACE2-expressing mice, immunized hACE2-mice. We...
Mast cells are multifunctional immune scattered in tissues near blood vessels and mucosal surfaces where they mediate important reactions against parasites contribute to the pathogenesis of allergic reactions. Serine proteases released from secretory granules upon mast cell activation these functions by modulating cytokine activity, platelet proteolytic neutralization toxins. The forced release granule into cytosol induce suicide has recently been proposed as a therapeutic approach reduce...
Multiple enveloped RNA viruses of the family Paramyxoviridae and Pneumoviridae, like measles virus (MeV), Nipah (NiV), canine distemper (CDV), or respiratory syncytial (RSV), are high clinical relevance. Each year a huge number lives lost as result these viral infections. Worldwide, MeV infection alone is responsible for over hundred thousand deaths each despite available vaccine. Therefore, there an urgent need treatment options to counteract The development antiviral drugs in general...
Here, we present a protocol to analyze the T cell profiles of neonatal ovine lung during respiratory syncytial virus (RSV) infection. The delivers standardized multiparameter flow cytometry (FCM) analysis CD4+, CD8+, regulatory, and γδ cells isolated from lung, lymph nodes, bronchoalveolar lavages (BALs). We detail preparation RSV transtracheal inoculation newborn lambs. then describe tissue isolation suspensions, followed by FCM acquisition identify different subsets. For complete details...
ABSTRACT The recent coronavirus disease 2019 (COVID-19) outbreak revealed the susceptibility of elderly patients to respiratory virus infections, showing cell senescence or subclinical persistent inflammatory profiles and favouring development severe pneumonia. In our study, we evaluated potential influence lung aging on efficiency replication influenza A (IAV) acute syndrome 2 (SARS-CoV-2), as well determined pro-inflammatory antiviral responses distal tissue. Using precision-cut slices...
We present a protocol to generate an advanced ex vivo model of human placenta. use vibrating tissue slicer obtain precision-cut slices representative the entire thickness This approach delivers standardized cultures with preserved microstructure and cellular composition comparable native tissue. applied this system study SARS-CoV-2 infection at maternal-fetal interface. Moreover, can be used investigate basic functions placenta in health disease. For complete details on execution protocol,...
ABSTRACT Lung-resident (LR) mesenchymal stem and stromal cells (MSCs) are key elements of the alveolar niche fundamental regulators homeostasis regeneration. We interrogated their function during virus-induced lung injury using highly prevalent respiratory syncytial virus (RSV) which causes severe outcomes in infants. applied complementary approaches with primary pediatric LR-MSCs a state-of-the-art model human RSV infection lamb. Remarkably, RSV-infection led to robust activation,...
<title>Abstract</title> Vaccines are the most effective measure against COVID-19. However, novel and highly efficacious vaccines with simplified administration broad immunogenicity, providing systemic mucosal immunity needed. Here, we show development of live-attenuated (LAV) based on (i) recoding SARS-CoV-2 genome to enrich for "one-to-stop" (OTS) codons, (ii) facilitating host responses by disabling non-structural-protein-1 (Nsp1) mediated translational repression, deletion open reading...
Mesenchymal stromal/stem cells (MSCs) are multipotent with regenerative and immunomodulatory properties, found perivascular in most organs, including the respiratory tract. Due to their strategic location, lung resident-MSCs (LR-MSCs) believed support local cellular microenvironment play a role modulation of pulmonary immune response. Consequently, we aimed at characterization paediatric LR-MSCs terms phenotypical markers, transdifferentiation capacity cytokine profiles baseline conditions...
βThe human respiratory syncytial virus (RSV) is the leading cause of lower tract infection during early childhood and infancy. There no vaccine very limited therapeutic options available. The mechanisms underlying severity RSV are not fully understood. Although loads correlating with disease severity, numerous studies report that an inappropriate immune response contributes to as well, either through overexuberant inflammatory response, towards a biased Th2 response. Recently, neonatal lamb...
ABSTRACT The human respiratory syncytial virus (RSV) is a major cause of severe lower tract infections in infants, possibly due to the specific features immature neonatal pulmonary immune system. Using newborn lamb, classical model lung development and state-of-the-art RSV infection, we aimed explore role cell-mediated immunity disease during early life. Remarkably, healthy conditions, developing T cell compartment showed differences that seen mature adult lung. most striking observation...