Biology subjects

Vanhoorelbeke, K.

Publications and source records attributed to Vanhoorelbeke, K..

3 recordsLinked to original sources

bioRxiv2021

Anti-SARS-CoV-2 human antibodies retaining neutralizing activity against SARS-CoV-2 B.1.1.529 (omicron)

SARS-CoV-2 B.1.1.529, designated omicron, was recently identified as a new variant of concern by WHO and is rapidly replacing SARS-CoV-2 delta as the most dominant variant in many countries. Unfortunately, because of the high number of mutations present in the spike of SARS-CoV-2 omicron, most monoclonal antibodies (mAbs) currently approved for treatment of COVID-19 lose their in vitro neutralizing activity against this variant. We recently described a panel of human anti-SARS-CoV-2 mAbs that potently neutralize SARS-CoV-2 Wuhan, D614G and variants alpha, beta, gamma and delta. In this work, we evaluated our mAb panel for potential in vitro activity against SARS-CoV-2 delta and omicron. Three mAbs from our panel retain neutralizing activity against both delta and omicron, with mAb 3B8 still resulting in complete neutralization at a concentration as low as 0.02 g/ml for both variants. Overall, our data indicate that mAb 3B8 may have the potential to become a game-changer in the fight against the continuously evolving SARS-CoV-2.

immunology↗

bioRxiv2021

Potent neutralizing anti-SARS-CoV-2 human antibodies cure infection with SARS-CoV-2 variants in hamster model

Treatment with neutralizing monoclonal antibodies (mAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contributes to COVID-19 management. Unfortunately, SARS-CoV-2 variants can escape several of these recently approved mAbs, highlighting the need for additional discovery and development. In a convalescent COVID-19 patient, we identified six mAbs, classified in four epitope groups, that potently neutralized SARS-CoV-2 Wuhan, alpha, beta, gamma and delta infection in vitro. In hamsters, mAbs 3E6 and 3B8 potently cured infection with SARS-CoV-2 Wuhan, beta and delta when administered post-viral infection at 5 mg/kg. Even at 0.2 mg/kg, 3B8 still reduced viral titers. Intramuscular delivery of DNA-encoded 3B8 resulted in in vivo mAb production of median serum levels up to 90 g/ml, and protected hamsters against delta infection. Overall, our data mark 3B8 as a promising candidate against COVID-19, and highlight advances in both the identification and gene-based delivery of potent human mAbs.

immunology↗

bioRxiv2020

The GPIbα intracellular tail - role in transducing VWF- and Collagen/GPVI-mediated signaling

Synergy between GPIb and GPVI signaling machineries has been suggested previously, however its molecular mechanism remains unclear. We generated a novel GPIb transgenic mouse (GPIb{Delta}sig/{Delta}sig) by CRISPR-Cas9 technology to delete the last 24 residues of the GPIb intracellular tail important for VWF-mediated signaling. GPIb{Delta}sig/{Delta}sig platelets bound VWF normally under flow but formed fewer filopodia on VWF/botrocetin, demonstrating that the deleted region does not affect ligand binding but appreciably impairs VWF-dependent signaling. Notably, while haemostasis was normal in GPIb{Delta}sig/{Delta}sig mice, GPIb{Delta}sig/{Delta}sig platelets exhibited defective responses after collagen-related-peptide stimulation and formed smaller aggregates on collagen-coated microchannels at low and high shears. Flow assays performed with plasma-free blood or in the presence of IIb{beta}3-or GPVI-blockers suggested reduced IIb{beta}3 activation contributes to the phenotype of the GPIb{Delta}sig/{Delta}sig platelets. Together, these results reveal a new role for the intracellular tail of GPIb in transducing both VWF-GPIb and collagen-GPVI signaling events in platelets. Summary statementGPIb and GPVI are two key receptors on the platelet surface. Using a novel transgenic mouse (GPIb{Delta}sig/{Delta}sig) that lacks the last 24 amino acids of the GPIb intracellular tail, we demonstrate the importance of this region not only in transducing signals in response to GPIb binding to VWF, but also for collagen-GPVI-mediated platelet responses revealing previously underappreciated receptor crosstalk between GPIb and GPVI.

cell biology↗