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6 Jan, 6 tweets, 3 min read
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
And that S2K146 affinity maturation allows it to be more resilient to mutations (including all individual mutations found in #OmicronVariant) than the unmutated germline precursor

4/5 Image
Finally, we showed in this recent paper that S2K146 potently neutralizes the #OmicronVariant !

5/5
nature.com/articles/d4158…
Thanks @Nature for highlighting our work!

nature.com/articles/d4158…

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More from @veeslerlab

The Veesler Lab Profile picture
31 Dec 21
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
The Veesler Lab Profile picture
21 Dec 21
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
The Veesler Lab Profile picture
14 Dec 21
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
The Veesler Lab Profile picture
10 Dec 21
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
The Veesler Lab Profile picture
26 Oct 21
Have you heard of the recently discovered 8th human-infecting #coronavirus designated CCoV-HuPn-2018?
We reveal the architecture of its spike (ie infection machinery), receptor usage and antigenic properties!

Led by @aletortorici

1/12

biorxiv.org/content/10.110…
CCoV-HuPn-2018 is a canine-feline recombinant alpha-#coronavirus isolated from the respiratory swab of a child hospitalized with pneumonia, indicating that more coronaviruses are spilling over to humans than previously appreciated.

2/12

academic.oup.com/cid/advance-ar…
We determined #cryoEM structures of the CCoV-HuPn-2018 spike in two markedly different conformational states which we propose to correspond to two snapshots of viral entry.

3/12
Read 12 tweets
The Veesler Lab Profile picture
14 Oct 21
We identified a broadly neutralizing sarbecovirus antibody (S2K146) in collaboration with Matteo Samuele Pizzuto & @DavideCorti6
Work led by @YoungjunPark11 Anna De Marco @tylernstarr @JZhuoming

1/7
biorxiv.org/content/10.110…
S2K146 binds and broadly neutralizes several SARS-CoV-1-like and SARS-CoV-2-like viruses (clades 1a/1b). It inhibits BtKY72 (clade 3) K493Y/T498W S pseudovirus, as we previously showed that these 2 mutations enable this bat virus to use hACE2.

biorxiv.org/content/10.110…

2/7 Image
Our #cryoEM structure reveals that S2K146 'mimics' ACE2, as 75% of the residues participating in the epitope are also part of the ACE2 binding site, and is therefore not affected by known variants.

3/7 Image
Read 7 tweets

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