Bloom Lab

@[email protected]
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Lab studying molecular evolution of proteins and viruses. Affiliated with Fred Hutch and HHMI.
Lab websitehttp://research.fhcrc.org/bloom/en.html
Google Scholarhttps://scholar.google.com/citations?user=S12x_eQAAAAJ&hl=en
Twitterhttps://twitter.com/jbloom_lab
Show threadBloom LabAug 31, 2023
Adding to this thread, Yunlong Cao has posted the first experimental data on neutralization escape by BA.2.86: https://twitter.com/yunlong_cao/status/1697318194976010446
Yunlong Richard Cao on X

Sharing some new experimental data on BA.2.86: 1) BA.2.86 is antigenically distinct compared to XBB.1.5. 2) BA.2.86 can significantly escape XBB-infection/vaccination induced antibodies. 3) However, the infectivity of BA.2.86 may be much lower than XBB.1.5 and EG.5. (1/n)

X (formerly Twitter)
Show threadBloom LabAug 30, 2023

More broadly, please interactively explore the new deep mutational scanning data at https://dms-vep.github.io/SARS-CoV-2_XBB.1.5_spike_DMS/htmls/summary_overlaid.html

We hope to post full pre-print related to these data within next month.

Show threadBloom LabAug 30, 2023
Mutations at site 420 cause appreciable escape, and also are well tolerated in deep mutational scanning. So not sure why such mutations not more widespread in nature? I guess a reminder that deep mutational scanning isn’t measuring everything that shapes real evolution!
Show threadBloom LabAug 30, 2023
Mutations at site 456 cause appreciable escape, and are reasonably tolerated for ACE2 affinity. Likely why F456L is becoming widespread in XBB descendants. Note @yunlong_cao & David Ho have both already shown F456L causes ~2-fold drop in XBB neutralization.
Show threadBloom LabAug 30, 2023
Mutations at site 357 also cause substantial escape. However, most (but not all) mutations at this site are at least moderately bad for ACE2 affinity. Note that mutations like K356T (which add N-linked glycan at site 354) also may escape some of these antibodies.
Show threadBloom LabAug 30, 2023

Going through these top escape sites:

Mutations at site 473 cause substantial decrease in neutralization by XBB breakthrough sera. However, mutations at this site are also fairly bad for ACE2 affinity, creating a high barrier for such mutations to spread.

Show threadBloom LabAug 30, 2023

Experiments map sites in XBB spike where mutations escape neutralization by sera of humans w recent XBB infection

(Antibody response depends on exposure history, so escape may differ for other exposures not studied here)

Greatest escape is at sites 473, 357, 455/456, 420

Bloom LabAug 30, 2023

Here are data from new XBB.1.5 spike deep mutational scanning by Bernadeta Dadonaite in our group

Go to https://dms-vep.github.io/SARS-CoV-2_XBB.1.5_spike_DMS/htmls/summary_overlaid.html to see how mutations affect:

1⃣ Neutralization by human XBB breakthrough sera

2⃣ Spike-mediated pseudovirus entry in 293T-ACE2 cells

3⃣ Affinity for ACE2

It will be few weeks before we finish pre-print for study, but we wanted to share data now for those interested in SARS2 evolution

Measurements made using lentiviral deep mutational scanning: https://sciencedirect.com/science/article/pii/S0092867423001034

Show threadBloom LabAug 23, 2023

I have updated my BA.2.86 slides: https://slides.com/jbloom/new_2nd_gen_ba2_variant

Slides are still up-to-date with regards to spike protein mutations.

But enough BA.2.86 sequences have now identified that slides are no longer an effective way to track those.

Instead see this tree: https://nextstrain.org/groups/neherlab/ncov/BA.2.86

Also the results of wastewater sequencing: https://twitter.com/dr_leshan/status/1694368402624893045
https://twitter.com/TanjaStadler_CH/status/1694298380841996613

new_2nd_gen_BA2_variant

Analysis of spike mutations in new second-generation BA.2 variant with many mutations

Slides
Show threadBloom LabAug 22, 2023

I have updated my slides to reflect identification of 7th sequence of highly mutated BA.2.86 lineage: https://slides.com/jbloom/new_2nd_gen_ba2_variant

For latest on details of BA.2.86 sequences, see this Nextstrain tree from @corneliusroemer @richardneher: https://twitter.com/CorneliusRoemer/status/1693957492399599765

new_2nd_gen_BA2_variant

Analysis of spike mutations in new second-generation BA.2 variant with many mutations

Slides