Our latest work with @VirusWhisperer shows that the B.1.351 variant easily escapes Sputnik V vaccine elicited neutralizing antibodies. medrxiv.org/content/10.110…
Benhur’s data analyses are 👨🏽‍🍳’s 😘 .. and the amount of escape is just 👀 🤯
The system used here is a REPLICATION COMPETENT recombinant VSV carrying the SARS-CoV-2 Spike (or Spike from variants).. similar to systems used by @PaulBieniasz @ChandranLab @vsv512
One of the great advantages of working with Benhur’s lab is @csstevens91 @sope_oguntuyo developed a single cell cloned an optimized target cell expressing ACE2 & TMPRSS2.. makes for a super sensitive reporter system.
The degree to which B.1.351 escapes Sputnik V neutralization is just remarkable...
We should probably be using 2P or even HexaPro (h/t @McLellan_Lab) prefusion “locked” Spikes in updated vaccines, and update them to match the most concerning S: E484K-type variants.
Belated h/t @satoshi84570237 @sope_oguntuyo @GriffinHaas and the many other co-authors not on twitter for their essential contributions to the study!
my role was mainly to pitch incorporating into @VirusWhisperer's VSV-eGFP-Spike system the most frequent non-synonymous substitutions showing up from data shared via @GISAID by the amazing worldwide community of people doing Viral Genome Surveillance of SARS-CoV-2
Of course, as soon as B.1.1.7 and B.1.351 emerged, I also ordered gBlocks from @idtdna and started stitching them into Benhur's genomic clone of VSV-eGFP-Spike and the amazing @satoshi84570237 rescued them into live virus faster than anyone can believe. He is a wizard!
We have lots of other surprises in store but I'd like to drive home how ESSENTIAL it is to be able to trust others and to collaborate to do great science. Everyone has their special skills..
Benhur is particularly adroit at mathematical analyses of neutralization curves (Hill slope analysis, etc).. and also knows how to make cells with optimal receptor + co-receptor density to study entry in vitro.
One can learn so much working together with people like Benhur and his amazingly talented lab members. That's not just lip service. These people are all incredible.

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More from @macroliter

2 Apr
Re-reading this amazing @specterm piece from 2007 featuring @HarmitMalik @ArisKatzourakis @PaulBieniasz @memerman.. behind the scenes is Matt Stremlau's then recent discovery of TRIM5alpha, a factor that "restricts" certain retroviruses newyorker.com/magazine/2007/…
it's a favorite article of mine.. In fact, I always try to wheedle the medical students into reading it when I lecture on viral pathogenesis..and it's funny to realize it must have been some years since I read it in full.
so much admiration for the incredible journeys of imagination, curiosity, and hard work that goes into solving these riddles..
Read 7 tweets
2 Apr
😡. Dr. Heguy has been working tirelessly to serve the viral genomic surveillance needs of New Yorkers since beginning of the pandemic.
She’s one of the best in the world at sequencing & genomics. Her important work has been covered by @carlzimmer. nytimes.com/2020/04/08/sci…
She works at an academic medical center rooted in the NYC community. Yet @nycHealthy finds a way to spend New Yorker’s money contracting with a for-profit outfit instead of working with people like and her team @nyulangone or another at @IcahnMountSinai
Read 5 tweets
31 Mar
So lucky 🍀 to be watching @ACasadevall1 give a seminar on how fungi cause disease. Super fascinating! Cost of being an endotherm versus susceptibility to fungal disease. 🤯
One of the best talks I’ve ever seen. Hands down. He is talking about Cenotes, dinosaurs, flaming meteorites.. and it is just so so good.
Fungal proliferation at the k/t boundary “a perfect time for compost”. 🍄
Read 5 tweets
27 Mar
All 3 FDA authorized COVID-19 vaccines in use here in USA employ a prefusion “locked” Spike, a beautiful innovation developed by @McLellan_Lab @BarneyGrahamMD @KizzyPhD & others..
which results in superior antibody responses because it trains the immune response on the right target 🎯
This is important because the Spike (like all viral membrane fusion proteins has 2 forms: a prefusion form, and a postfusion form..
Read 14 tweets
26 Mar
Someone asked me today, "In two sentences or less could you answer the question “Why is Genome Sequencing important?”. . . I failed at the 2 sentences part, but...🧵
Sequencing the entire genomes of viruses, bacteria, and fungi that cause disease is called “genomic surveillance”
The sequencing technologies have gotten less and less expensive and at the same time far more powerful than ever before
Read 13 tweets
26 Mar
"Double Mutant" Report! Congrats & Thank you to scientists at India's CSIR-National Environmental Engineering Research Institute & Centre for Cellular & Molecular Biology/ INSACOG for sharing via @GISAID the🧬data for 36 new Spike L452R, E484Q from Maharashtra and West Bengal.
Many samples were from asymptomatic patients, and are all lineage B.1, and the S mutations on many / most of them are.. (36 of the 38 are also P681R, which prob increases processing of the polybasic site at the S1/S2 boundary)
D614G
E154K
E484Q
L452R
P681R
+/- T95I
+/- H1101D
Probably best not to call them "double mutant" as the news reports have.. but maybe sexta-mutant S 😆?
Read 9 tweets

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