Poster ESCMID Global 2024 Conference
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Poster presented by CSO Viki Bockstal at ESCMID Global, 27–30 April 2024 in Barcelona, Spain
Member spotlight: ExeVir uses llama-derived antibodies to protect the vulnerable
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MEDVIA article featuring ExeVir – Based on the interview with CSO, Viki Bockstal.
By Amy LeBlanc.
Images: Winter the llama ©Tim Coppens
Ultrapotent SARS coronavirus-neutralizing single-domain antibodies that bind a conserved membrane proximal epitope of the spike
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Currently circulating SARS-CoV-2 variants have gained complete or significant resistance to all SARSCoV-2-neutralizing antibodies that have been used in the clinic. Such antibodies can prevent severe disease in SARS-CoV-2 exposed patients for whom vaccines may not provide optimal protection. Here, we describe single-domain antibodies (VHHs), also known as nanobodies, that can broadly neutralize SARS-CoV-2 with unusually high potency. Structural analysis revealed their binding to a unique, highly conserved, membrane proximal, quaternary epitope in the S2 subunit of the spike. Furthermore, a VHH-human IgG1 Fc fusion, efficiently expressed in Chinese hamster ovary cells as a stable antibody construct, protected hamsters against SARS-CoV-2 replication in a therapeutic setting when administered systemically at low dose. This VHH-based antibody represents a new candidate anti-COVID-19 biologic that targets the Achilles heel of the viral spike.
Structural Basis for Potent Neutralization of Betacoronaviruses by Single-Domain Camelid Antibodies
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Using llamas immunized with prefusionstabilized betacoronavirus spike proteins, Wrapp et al. identify neutralizing cross-reactive single-domain camelid antibodies, which may serve not only as useful reagents for researchers studying the viruses causing MERS, SARS, and COVID-19, but also potential therapeutic candidates. Crystal structures further reveal how these antibodies bind spike proteins to prevent virus entry into cells.