The peer-reviewed version of our manuscript describing the structures of the #SARS_CoV_2 #OmicronVariant spike bound to the clinical S309 antibody (sotrovimab parent) and receptor-binding domain bound to ACE2 (and S309/S304) is now available here.

science.org/doi/10.1126/sc…

1/7
Here is the original thread describing this study



2/7
During the reviewing process, we added binding data to show that most clinical antibodies have reduced or abrogated binding to the #OmicronVariant spike trimer relative to Wuhan-Hu-1 spike

3/7
In agreement with the receptor-binding domain binding data that were already present in our @biorxivpreprint preprint

4/7
These data reflect the abrogated neutralization from these antibodies except for S309 (~3x drop) and COV2-2130/COV2-2196 (10-200x drop), as shown here

5/7

nature.com/articles/s4158…
We show that the S371L/S373P/S375F mutations enhance conformational dynamics of this region of the receptor-binding domain and hinder recognition of some antibodies targeting this site, suggesting these mutations arose (at least in part) to promote immune evasion.

6/7
Thanks again to @Dr_MattMcCallum Nadine Czudnochowski @SamK_Zepeda @johnbowenbio @coronalexington @CrollTristan @DavideCorti6 Gyorgy Snell & many others!

7/7

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More from @veeslerlab

Jan 26
Delighted to share our study of the #SARSCoV2 E406W spike mutant describing how a single amino acid mutation mediates escape from the REGN10987/REGN10933 antibody cocktail despite residing outside their epitopes

Led by @AminAddetia

1/8

biorxiv.org/content/10.110…
The E406W mutation was previously described by @tylernstarr @AllieGreaney (along with @AminAddetia during his rotation in) @jbloom_lab using deep-mutational scanning and neutralization assays.

2/8

science.org/doi/10.1126/sc…
We determined a #CryoEM structure of the E406W spike trimer and observed a remodeling of the receptor-binding domain (RBD), hindering binding of clinical antibodies such as the REGN10987/REGN10933 cocktail or COV2-2130

3/8 Image
Read 8 tweets
Jan 6
The peer-reviewed version of our manuscript describing the broadly neutralizing sarbecovirus antibody S2K146 can be found here

science.org/doi/10.1126/sc…

1/5
Here is the original thread describing these results.



2/5
Compared to our original @biorxivpreprint submission, we added data showing that S2K146 binds the reconstructed RBD ancestor of all sarbecoviruses (AncAsia)

3/5 Image
Read 6 tweets
Dec 31, 2021
We characterized the structural basis of #SARSCoV2 #OmicronVariant binding to the host ACE2 receptor and neutralization by the S309/sotrovimab clinical antibody therapeutic!

Led by @Dr_MattMcCallum & Nadine Czudnochowski Collab w Gyorgy Snell

1/8

biorxiv.org/content/10.110…
We show that the #OmicronVariant spike NTD antigenic supersite is structurally rearranged, relative to the Wuhan-Hu-1 NTD, explaining the loss of binding and neutralization by a panel of NTD-targeted monoclonal antibodies we recently evaluated (nature.com/articles/d4158…).

2/8
The #OmicronVariant spike S2 subunit (fusion machinery) harbors mutations introducing additional electrostatic contacts with the S1 subunit, which might explain the reduced S1 shedding described in this preprint (biorxiv.org/content/10.110…)

3/8
Read 8 tweets
Dec 21, 2021
Can we correlate #SARSCoV2 spike (S) biochemical properties with the specificity, magnitude & quality of antibody responses? Put another way, how to make a good #CovidVaccine ?

@johnbowenbio led the charge to answer these questions

@HHMINEWS

1/21

biorxiv.org/content/10.110…
We compared antibody responses elicited by 6 #CovidVaccine distributed globally: Moderna mRNA-1273, Pfizer/BioNTech BNT162b2, AstraZeneca AZD1222, Gamaleya Sputnik V and Sinopharm BBIBP-CorV, after 2 doses, Janssen Ad26.COV2.S after 1 dose, and human convalescent plasma

2/21
Prefusion S/S2, RBD & NTD antibody binding titers were highest after 2 doses of mRNA-1273 or BNT162b2 and lowest for 1 dose of Ad26.COV2.S. The other 2 dose vaccines and #SARSCoV2 infection resulted in intermediate binding titers.

3/21
Read 22 tweets
Dec 14, 2021
Here is our assessment of #SARSCoV2 #Omicron receptor usage and immune evasion in collaboration with the team of @DavideCorti6 @Vir_Biotech

Led by Elisabetta Cameroni, Christian Saliba, @johnbowenbio & Laura E. Rosen

@HHMINEWS @UWBiochemistry

biorxiv.org/content/10.110…

1/8
#SARSCoV2 #Omicron harbors a staggering 37 amino acid mutations in the spike with 15 of them in the receptor-binding domain (RBD), which is the main target of neutralizing antibodies. The number and positions of these mutations is concerning for tropism & immune evasion.

2/8
We found that the #SARSCoV2 #Omicron RBD has ~2.5-fold enhanced ACE2 binding affinity, relative to the Wuhan-Hu-1 RBD, similar to what we previously showed for the Beta variant of concern.

nature.com/articles/s4158…

3/8
Read 8 tweets
Dec 10, 2021
Are you wondering what antibody responses are like in #SARSCoV2 Delta breakthrough patients?

We answer this question and many others in this study led by @coronalexington

@HHMINEWS @UWBiochemistry

biorxiv.org/content/10.110…

1/15
We followed 4 cohorts longitudinally for up to 6 months:
-Delta breakthrough (vaccinated then infected)
-subjects infected and then vaccinated (2x and 3x)
-vaccinated-only (2x and 3x)
-infected-only

in collaboration with @HelenChuMD and her HAARVI team.

2/15
Serum IgG binding titers correlated with the number of SARS-CoV-2 spike 'exposures' through vaccination and/or infection and were therefore highest for 3x vaccinated subjects (infected or not) and Delta breakthrough cases.

3/15
Read 15 tweets

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