Structural Basis and Mode of Action for Two Broadly Neutralizing Antibodies Against SARS-CoV-2 Emerging Variants of Concern

Autor: Maolin Lu, Yuxia Bo, Jérémie Prévost, Wenwei Li, Fei Zhou, William D. Tolbert, Irfan Ullah, Romain Gasser, Di Xia, Allison Zeher, Yaozong Chen, Pradeep D. Uchil, Andrés Finzi, Marzena Pazgier, Michael W Grunst, Jonathan Richard, Priti Kumar, Shijian Zhang, Shilei Ding, Sai Priya Anand, Joseph Sodroski, Dani Vézina, Lothar Esser, Alexandra Tauzin, Marceline Côté, Rick Huang, Guillaume Goyette, Debashree Chaterjee, Walther Mothes, Shang Yu Gong
Rok vydání: 2021
Předmět:
Zdroj: Cell Reports
bioRxiv
DOI: 10.1101/2021.08.02.454546
Popis: Emerging variants of concern for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can transmit more efficiently and partially evade protective immune responses, thus necessitating continued refinement of antibody therapies and immunogen design. Here we elucidate the structural basis and mode of action for two potent SARS-CoV-2 Spike (S) neutralizing monoclonal antibodies CV3-1 and CV3-25 that remain effective against emerging variants of concern in vitro and in vivo. CV3-1 binds to the (485-GFN-487) loop within the receptor-binding domain (RBD) in the “RBD-up” position and triggers potent shedding of the S1 subunit. In contrast, CV3-25 inhibits membrane fusion by binding to an epitope in the stem helix region of the S2 subunit that is highly conserved among β-coronaviruses. Thus, vaccine immunogen designs that incorporate the conserved regions in RBD and stem helix region are candidates to elicit pan-coronavirus protective immune responses.
Graphical Abstract
Li et al. elucidate the structural basis and mode of action for two potent anti-Spike neutralizing monoclonal antibodies that remain effective against SARS-CoV-2 emerging variants of concern. Vaccine immunogen designs based on both conserved epitopes are candidates to elicit pan-coronavirus protective immune responses.
Databáze: OpenAIRE
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