The Veesler Lab Profile picture
Studies of pathogen entry into cells, host immune responses & vaccine design: structural biology, immunology, virology, genomics @HHMINEWS @UWBiochemistry
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May 10 24 tweets 14 min read
We analyzed human plasma, mucosal and memory antibody responses against #SARSCoV2 and found a pan-variant neutralizing antibody!

Led by @YoungjunPark11 Dora Pinto @coronalexington @JZhuoming

Collab. with @DavideCorti6

@HHMINEWS
@Vir_Biotech

1/24

biorxiv.org/content/10.110… We assessed plasma neutralizing activity from humans previously infected in 2020 (WA-1-like) and then vaxed 2x or 3x, or vaxed before Delta or #Omicron BA.1 breakthrough infection or vaxed-'only' 3x

2/24
Mar 17 13 tweets 7 min read
Excited to share our latest serological data evaluating plasma neutralizing antibody responses and immune evasion associated with the constellation of spike mutations present in the #Omicron BA.1 and BA.2 variants.

Led by @johnbowenbio

1/13

biorxiv.org/content/10.110… We compared side-by-side the plasma neutralizing activity elicited in humans by seven #COVID19 vaccines (Moderna, Pfizer, Novavax, Janssen, AstraZeneca, Sputnik V and Sinopharm) or SARS-CoV-2 Washington-1 infection. We cover mRNA, Ad-vectored and protein subunit vaccines!

2/13
Feb 9 6 tweets 4 min read
Throughout the pandemic, we have been puzzled with inconsistencies in the observed breadth of polyclonal serum neutralizing antibodies against #SARSCoV2 variants in mice vs humans or non-human primates.

Led by @coronalexington

@HHMINEWS

1/6

biorxiv.org/content/10.110… Serum neutralizing antibodies titers represent the current best correlate of protection against #SARSCoV2 used to evaluate and compare vaccine-elicited immunity in animal models and humans.

For an example see this paper.

2/6

nature.com/articles/s4158…
Jan 26 8 tweets 6 min read
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…
Jan 25 7 tweets 4 min read
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
Jan 6 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
Dec 31, 2021 8 tweets 5 min read
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
Dec 21, 2021 22 tweets 12 min read
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
Dec 14, 2021 8 tweets 9 min read
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
Dec 10, 2021 15 tweets 8 min read
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
Oct 26, 2021 12 tweets 6 min read
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…
Oct 14, 2021 7 tweets 5 min read
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
Aug 11, 2021 9 tweets 5 min read
Sharing our latest preprint on #SARSCoV2 B.1.617.2 (delta), B.1.617.2+ (delta+) and B.1.617.1 (kappa) variants led by @Dr_MattMcCallum

1/9

biorxiv.org/content/10.110… We show that vaccine-elicited neutralizing activity is reduced against delta and kappa and even more against delta+ relative to the vaccine-matched pseudovirus. Delta+ reduces neutralization ~ to B.1.351 (beta) which has the greatest magnitude of immune evasion thus far.

2/9
Apr 1, 2021 7 tweets 5 min read
The #SARSCoV2 CAL20.C (B.1.427/B.1.429) variant is skyrocketing in California. We describe how it evades the host immune response with @DavideCorti6 @LucaPiccoli9

Led by @Dr_MattMcCallum, Jessica Bassi, Anna De Marco, Alex Chen & @coronalexington

1/7

biorxiv.org/content/10.110… The #SARSCoV2 CAL20.C (B.1.427/B.1.429) variant comprises 3 spike mutations: S13I, W152C & L452R reducing plasma neutralizing activity by ~3x and ~5x for vaccine- and infection-elicited antibodies (Abs), compared to the 'ancestral' virus.

2/7
Jan 14, 2021 10 tweets 7 min read
We report an analysis of #SARSCoV2 spike NTD antigenic sites targeted by monoclonal antibodies (mAbs) in #COVID19 patients in collaboration with @DavideCorti6 and Matteo Samuele Pizzuto @Vir_Biotech

Work led by @Dr_MattMcCallum & Anna De Marco

1/10

biorxiv.org/content/10.110… We found that NTD-specific mAbs account for 6-20% of mAbs cloned from memory B cells in #COVID19 patients and that the most potent of them neutralize #SARSCoV2 as efficiently as ultrapotent RBD-specific mAbs and trigger Fc-mediated effector functions effectively.

2/10
Dec 30, 2020 6 tweets 4 min read
We discovered a neutralizing mouse monoclonal antibody (B6) targeting the coronavirus spike fusion machinery (S2 subunit) in collaboration with @McGuire_Lab

Work led by @MaxMSauer

biorxiv.org/content/10.110…

1/6
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.

2/6
Oct 30, 2020 6 tweets 4 min read
The peer-reviewed version of our article describing the design and evaluation of a multivalent #SARSCoV2 receptor-binding domain #COVID19 vaccine is out!

Work Led by @coronalexington and Brooke Fiala.

cell.com/cell/fulltext/…

1/6
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.

cell.com/cell/fulltext/…

2/6