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We discovered a broadly neutralizing sarbecovirus monoclonal antibody (mAb) in collaboration with @DavideCorti6 & Matteo Samuele Pizzuto
Led by @aletortorici Nadine Czudnochowski, @tylernstarr & Roberta Marzi
1/10 https://www.biorxiv.org/content/10.1101/2021.04.07.438818v1
Led by @aletortorici Nadine Czudnochowski, @tylernstarr & Roberta Marzi
1/10 https://www.biorxiv.org/content/10.1101/2021.04.07.438818v1
S2X259 mAb uniquely cross-reacts with 29 spike glycoproteins representative of all sarbecovirus clades and broadly neutralizes #SARSCoV2 (including all variants of concern) a well as a broad panel of ACE2-utilizing sarbecoviruses with comparable potencies
2/10
2/10
S2X259-mediated broad sarbecovirus neutralization results from the conservation of its (cryptic) epitope among sarbecovirus clades and from the angle of approach allowing the mAb to circumvent the SARS-CoV N357 glycan present in all sarbecovirus RBDs except #SARSCoV2
3/10
3/10
Deep-mutational scanning from @tylernstarr @jbloom_lab and in vitro passaging with mAb from @JZhuoming @vsv512 identified G504, specifically G504D, as the only escape mutation for S2X259 (due to sterics). G504D is a very rare mutation found in 0.0014% of #SARSCoV2 genomes.
4/10
4/10
These results point to a high barrier for the emergence of S2X259 resistance mutants, which might prove essential during the next stages of the pandemic, where increasing immune pressure and continuing spread of the virus might result in the emergence of new variants.
5/10
5/10
S2X259 contacts a few residues involved in ACE2 binding and therefore blocks viral attachment to the host cell surface. S2X259 also promotes S1 subunit shedding through conformational selection for open RBDs
More about this in this thread
https://twitter.com/veeslerlab/status/1379091995990257670
6/10
More about this in this thread
https://twitter.com/veeslerlab/status/1379091995990257670
6/10
S2X259 protects Syrian hamsters against #SARSCoV2 challenge with prototypic (Wuhan) as well as with the B.1.351 variant of concern. We also show that S2X259 can be combined with S309 to protect against the B.1.351 variant of concern!
7/10
7/10
S2X259 is a promising candidate for clinical development which could be stockpiled as part of a pandemic preparedness toolbox. Our data also support the development of RBD vaccines to elicit broad sarbecovirus protection led by @coronalexington
8/10 https://www.biorxiv.org/content/10.1101/2021.03.15.435528v1
8/10 https://www.biorxiv.org/content/10.1101/2021.03.15.435528v1
Thank you @coronalexington @johnbowenbio Zhaoqian Wang @SamK_Zepeda and all our wonderful collaborators including @neyts_johan & many others!
9/10
9/10
Please check out our companion paper with an in-depth analysis of RBD-specific mAb binding and neutralization properties led by @tylernstarr @jbloom_lab @DavideCorti6 & Gyorgy Snell
10/10 https://www.biorxiv.org/content/10.1101/2021.04.06.438709v1
10/10 https://www.biorxiv.org/content/10.1101/2021.04.06.438709v1
