A5002777079- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- Animal Virus Infections Studies
- Respiratory viral infections research
- SARS-CoV-2 detection and testing
- Viral gastroenteritis research and epidemiology
- Virus-based gene therapy research
- Long-Term Effects of COVID-19
- COVID-19 epidemiological studies
- Lung Cancer Research Studies
- CRISPR and Genetic Engineering
- Bacillus and Francisella bacterial research
- Inhalation and Respiratory Drug Delivery
- Glycosylation and Glycoproteins Research
- Influenza Virus Research Studies
- vaccines and immunoinformatics approaches
- Polyomavirus and related diseases
- Viral Infections and Outbreaks Research
- Monoclonal and Polyclonal Antibodies Research
- Phagocytosis and Immune Regulation
- Heme Oxygenase-1 and Carbon Monoxide
- Congenital Diaphragmatic Hernia Studies
- Bacteriophages and microbial interactions
- Pharmacological Receptor Mechanisms and Effects
- Legionella and Acanthamoeba research
Erasmus MC
2020-2025
Erasmus University Rotterdam
2021-2024
Utrecht University
2023
Universitat Autònoma de Barcelona
2023
Centre de Recerca en Sanitat Animal
2023
University of Hong Kong
2023
Intestinal organoids as an infection model Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes influenza-like disease with a transmission route; however, patients often present gastrointestinal symptoms such diarrhea, vomiting, and abdominal pain. Moreover, the virus has been detected in anal swabs, cells inner-gut lining express receptor that SARS-CoV-2 uses to gain entry cells. Lamers et al. used human intestinal organoids, “mini-gut” cultured dish, demonstrate readily...
The severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) Omicron variant is spreading rapidly, even in vaccinated individuals, raising concerns about immune escape. Here, we studied neutralizing antibodies and T cell responses targeting SARS-CoV-2 D614G [wild type (WT)] the Beta, Delta, variants of concern a cohort 60 health care workers after immunization with ChAdOx-1 S, Ad26.COV2.S, mRNA-1273, or BNT162b2. High binding antibody levels against WT spike (S) were detected 28...
Article11 January 2021Open Access Transparent process An organoid-derived bronchioalveolar model for SARS-CoV-2 infection of human alveolar type II-like cells Mart M Lamers orcid.org/0000-0002-1431-4022 Viroscience Department, Erasmus University Medical Center, Rotterdam, The NetherlandsThese authors contributed equally to this work Search more papers by author Jelte van der Vaart orcid.org/0000-0002-4126-8420 Oncode Institute, Hubrecht Royal Netherlands Academy Arts and Sciences Utrecht,...
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is continuing to disrupt personal lives, global healthcare systems, and economies. Hence, there an urgent need for a vaccine that prevents viral infection, transmission, disease. Here, we present two-component protein-based nanoparticle displays multiple copies of the SARS-CoV-2 spike protein. Immunization studies show this induces potent neutralizing antibody responses in mice, rabbits, cynomolgus macaques....
Abstract COVID-19, caused by SARS-CoV-2, is an influenza-like disease with a respiratory route of transmission, yet clinical evidence suggests that the intestine may present another viral target organ. Indeed, SARS-CoV-2 receptor angiotensin converting enzyme 2 (ACE2) highly expressed on differentiated enterocytes. In human small intestinal organoids, enterocytes were readily infected SARS-CoV and as demonstrated confocal- electron-microscopy. Consequently, significant titers infectious...
The emergence and rapid spread of SARS-CoV-2 variants may affect vaccine efficacy substantially. Omicron variant termed BA.2, which differs substantially from BA.1 based on genetic sequence, is currently replacing in several countries, but its antigenic characteristics have not yet been assessed. Here, we used cartography to quantify visualize differences between early (614G, Alpha, Beta, Gamma, Zeta, Delta, Mu) using hamster antisera obtained after primary infection. We first verified that...
Coronavirus entry is mediated by the spike protein that binds receptor and mediates fusion after cleavage host proteases. The proteases mediate differ between cell lines, it currently unclear which are relevant in vivo. A remarkable feature of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presence a multibasic site (MBCS), absent SARS-CoV spike. Here, we report SARS-CoV-2 MBCS increases infectivity on human airway organoids (hAOs). Compared with SARS-CoV, entered faster into...
Transmission of severe acute respiratory coronavirus-2 (SARS-CoV-2) between livestock and humans is a potential public health concern. We demonstrate the susceptibility rabbits to SARS-CoV-2, which excrete infectious virus from nose throat upon experimental inoculation. Therefore, investigations on presence SARS-CoV-2 in farmed should be considered.
Virus propagation methods generally use transformed cell lines to grow viruses from clinical specimens, which may force rapidly adapt culture conditions, a process facilitated by high viral mutation rates. Upon in VeroE6 cells, SARS-CoV-2 mutate or delete the multibasic cleavage site (MBCS) spike protein. Previously, we showed that MBCS facilitates serine protease-mediated entry into human airway cells (Mykytyn et al., 2021). Here, report propagating on line Calu-3 – expresses proteases...
Abstract Rapid identification of host genes essential for virus replication may expedite the generation therapeutic interventions. Genetic screens are often performed in transformed cell lines that poorly represent viral target cells vivo, leading to discoveries not be translated clinic. Intestinal organoids increasingly used model human disease and amenable genetic engineering. To discern which factors reliable anti-coronavirus targets, we generate mutant clonal IOs 19 previously implicated...
The ongoing evolution of SARS-CoV-2 has resulted in the emergence Omicron, which displays notable immune escape potential through mutations at key antigenic sites on spike protein. Many these localize to protein ACE2 receptor binding domain, annulling neutralizing activity therapeutic antibodies that were effective against other variants concern (VOCs) earlier pandemic. Here, we identified a receptor-blocking human monoclonal antibody, 87G7, retained potent vitro including Alpha, Beta,...
Abstract The emergence and rapid spread of SARS-CoV-2 variants may impact vaccine efficacy significantly 1 . Omicron variant termed BA.2, which differs genetically substantially from BA.1, is currently replacing BA.1 in several countries, but its antigenic characteristics have not yet been assessed 2,3 Here, we used cartography to quantify visualize differences between using hamster sera obtained after primary infection. Whereas early are antigenically similar, clustering relatively close...
Abstract In late 2021, the highly mutated SARS-CoV-2 Omicron variant emerged, raising concerns about its potential extensive immune evasion, increased transmissibility and pathogenicity. Here, we used organoids of human airways alveoli to investigate Omicron’s fitness replicative in comparison with earlier variants. We report that replicates more rapidly has an compared early 614G Delta. contrast, did not replicate productively alveolar type 2 cells. Mechanistically, show does efficiently...
SARS-CoV-2 can enter cells after its spike protein is cleaved by either type II transmembrane serine proteases (TTSPs), like TMPRSS2, or cathepsins. It now widely accepted that the Omicron variant uses TMPRSS2 less efficiently and instead enters via cathepsins, but these findings have yet to be verified in more relevant cell models. Although we could confirm efficient cathepsin-mediated entry for a monkey kidney line, experiments with protease inhibitors showed (BA.1 XBB1.5) did not use...
Mucins play an essential role in protecting the respiratory tract against microbial infections while also acting as binding sites for bacterial and viral adhesins. The heavily O-glycosylated gel-forming mucins MUC5AC MUC5B eliminate pathogens by mucociliary clearance. Transmembrane MUC1, MUC4, MUC16 can restrict invasion at apical surface of epithelium. In this study, we determined impact host mucin glycans on epithelial entry SARS-CoV-2. Human lung Calu-3 cells express SARS-CoV-2 receptor...
ABSTRACT Human metapneumovirus (HMPV), a member of the Pneumoviridae family, causes upper and lower respiratory tract infections in humans. In vitro studies with HMPV have mostly been performed monolayers undifferentiated epithelial cells. vivo cynomolgus macaques cotton rats shown that ciliated cells are main target infection, but these observations cannot be studied monolayer systems. Here, we established an organoid-derived bronchial culture model allows physiologically relevant on HMPV....
To study the effect of interferon-α2 auto-antibodies (IFN-α2 Abs) on clinical and virological outcomes in critically ill COVID-19 patients risk IFN-α2 Abs transfer during convalescent plasma treatment.
The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires ongoing monitoring to judge the ability newly arising variants escape immune response. A surveillance system necessitates an understanding differences in neutralization titers measured different assays and using human animal serum samples. We compared 18 datasets generated human, hamster, mouse six assays. Datasets model samples showed higher titer magnitudes than this comparison. Fold change ancestral...
Abstract The severe acute respiratory distress syndrome coronavirus-2 (SARS-CoV-2) Omicron variant (B.1.1.529) is spreading rapidly, even in vaccinated individuals, raising concerns about immune escape. Here, we studied neutralizing antibodies and T-cell responses to SARS-CoV-2 D614G (wildtype, WT), the B.1.351 (Beta), B.1.617.2 (Delta), B.1.1.529 (Omicron) variants of concern (VOC) a cohort 60 health care workers (HCW) after immunization with ChAdOx-1 S, Ad26.COV2.S, mRNA-1273 or BNT162b2....
The Middle East respiratory syndrome (MERS) is a disease caused by MERS coronavirus (MERS-CoV). In follow up to phase 1 trial, we perform longitudinal analysis of immune responses following immunization with the modified vaccinia virus Ankara (MVA)-based vaccine MVA-MERS-S encoding MERS-CoV-spike protein. Three homologous immunizations were administered on days 0 and 28 late booster vaccination at 12 ± 4 months. Antibody isotypes, subclasses, neutralization capacity as well T B cell...
ABSTRACT Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) encodes six accessory proteins (3a, 6, 7a, 7b, 8, and 9b) for which limited information is available on their role in pathogenesis. We showed that the deletion of open reading frames (ORFs) or 7b individually did not significantly impact viral pathogenicity humanized K18-hACE2 transgenic mice. In contrast, ORF8 partially attenuated SARS-CoV-2, resulting reduced lung pathology 40% less mortality, indicating a critical...
Abstract Antigenic characterization of newly emerging SARS-CoV-2 variants is important to assess their immune escape and judge the need for future vaccine updates. To bridge data obtained from animal sera with human sera, we analyzed neutralizing antibody titers in hamster single infection a highly controlled setting using same authentic virus neutralization assay performed one laboratory. Using Bayesian framework, found that titer fold changes corresponded well generally exhibited higher reactivity.