We discovered a neutralizing mouse monoclonal antibody (B6) targeting the coronavirus spike fusion machinery (S2 subunit) in collaboration with @McGuire_Lab
We identified by cryoEM that B6 recognizes the spike stem helix and cross-reacts with at least 8 distinct coronavirus spikes including those of the three highly pathogenic (#SARSCoV2, SARS-CoV and MERS-CoV) and the two endemic (OC43 and HKU1) human β-coronaviruses.
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B6 broadly neutralizes spike-mediated entry into cells of distantly related coronaviruses including OC43 (lineage A) as well as MERS-CoV and HKU4 (lineage C) with comparable potencies.
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Our data indicate that B6 recognizes a cryptic linear epitope and suggest that it sterically interferes with the spike conformational changes leading to membrane fusion.
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Check out these two complementary studies showing that MERS-CoV and #SARSCoV2 infections elicit stem-directed antibodies binding to an epitope similar to the one targeted by B6!
The peer-reviewed version of our article describing the design and evaluation of a multivalent #SARSCoV2 receptor-binding domain #COVID19 vaccine is out!
Based on our previous studies of the immune response to coronavirus infections, we identified that the receptor-binding domain is immunodominant and accounts for most of the neutralizing activity in convalescent plasma/sera.
We therefore reached out to @KingLabIPD who had recently developed a self-assembling two component protein nanoparticle platform allowing to multivalently display respiratory syncytial virus F that elicit high-titers of neutralizing antibodies.