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Bloom Lab

@jbloom_lab

25 Nov

Here's how mutations in #SARSCoV2 Nu variant (B.1.1.529) will affect polyclonal and monoclonal antibodies targeting RBD. These assessments based on deep-mutational scanning experiments; underlying data can be explored interactively at jbloomlab.github.io/SARS2_RBD_Ab_e… (1/n)

First, Nu variant has lot of antigenic change. Below are how mutations relate to escape averaged over 36 human antibodies. Many mutations at peak escape sites, especially E484, G446, K417, & Q493. This means even in polyclonal mix, lot of RBD antibodies will be affected. (2/n)

@bjorkmanlab

Another way to assess polyclonal escape is how many epitope classes affected (nature.com/articles/s4146…). We do this using epitope scheme of @bjorkmanlab @cobarnes27 as adopted by @AllieGreaney. In this scheme, three potently neutralizing epitopes: class 1, 2, class 3. (3/n)

Read 23 tweets

Bloom Lab

@jbloom_lab

21 Nov

@MichaelWorobey

I wanted to add to renewed discussion of early Wuhan #SARSCoV2 triggered by @MichaelWorobey's recent perspective (

https://twitter.com/MichaelWorobey/status/1461417259600023556

). Although some the Twitter discussion has deteriorated into lab leak vs zoonosis yelling, there's some interesting scientific substance (1/n)

@BallouxFrancois

First to clear up point of confusion, there isn't new data about patient zero. As @BallouxFrancois explains (

https://twitter.com/BallouxFrancois/status/1462173229070618627

), patient zero was infected probably at least ~1 month before mid-Dec cases @MichaelWorobey is discussing, possibly substantially earlier. (2/n)

@MichaelWorobey

Note this misunderstanding about patient zero comes from newspaper headlines, and isn't fault of @MichaelWorobey. In fact, he's done work suggesting patient zero was infected between mid-Oct to mid-Nov (science.org/doi/10.1126/sc…), although there's still a lot of uncertainty (3/n)

Read 25 tweets

Bloom Lab

@jbloom_lab

2 Nov

@RolandBakerIII

@RolandBakerIII I don't think this paper suggests people were exposed to #SARSCoV2 20 years ago. Rather, it suggests that at a very low frequency some human antibody gene rearrangements will bind strongly to the #SARSCoV2 RBD even in the absence of an immune response selecting for this. (1/n)

@RolandBakerIII

@RolandBakerIII This is not terribly surprising. For instance, it's known that even naive humans sometimes have a bit of antibody reactivity to the #SARSCoV2 RBD (see Fig 1B of this paper by @SCOTTeHENSLEY). Indeed, this type of rare low-level naive reactivity...

@RolandBakerIII

@RolandBakerIII @SCOTTeHENSLEY is the basis for an immune response, which must start with some binding.

Additionally, these antibodies have genes similar to IGHV3-53, which is known to naturally bind well to the RBD with minimal somatic hypermutation. (3/n)

Read 5 tweets

Bloom Lab

@jbloom_lab

14 Oct

@AllieGreaney

In a new study led by @AllieGreaney, we show that infection with a #SARSCoV2 variant elicits an antibody response with somewhat shifted specificity relative to early Wuhan-Hu-1-like viruses that were circulating early in the pandemic: biorxiv.org/content/10.110… (1/n)

@VirusesImmunity

It's now known that #SARSCoV2 variants have mutations that reduce neutralization by antibodies elicited by early viruses, which are source of spike in current vaccines. This figure from @VirusesImmunity shows neutralization drops for common variants:

https://twitter.com/VirusesImmunity/status/1447709980514295810

(2/n)

But do the antibodies elicited by infection with these variants have different specificities, such that humoral immunity from infection with variants will be differentially affected by specific mutations? (3/n)

Read 14 tweets

Bloom Lab

@jbloom_lab

7 Oct

https://twitter.com/lab_leak/status/1446127423309770768

To answer below question, most bat CoV don't bind human ACE2 strongly, but can happen incidentally in evolution. Presumably because some mutations that increase binding to bat ACE2s incidentally increase binding to human ACE2, which has substantial homology to bat ACE2s. (1/6)

https://twitter.com/lab_leak/status/1446127423309770768

@TheMenacheryLab

One example is recently described BANAL-20-52 bat CoV, which binds human ACE2 strongly (researchsquare.com/article/rs-871…). Another is SHC014 (ncbi.nlm.nih.gov/pmc/articles/P…), which @TheMenacheryLab @Baric_Lab showed infects human cells despite having evolved in bats. (2/6)

More broadly, we recently did large yeast-display survey of SARS-related CoV RBDs and found that some bind human ACE2 (and some ACE2s from other species) well despite being from bats (biorxiv.org/content/10.110…). (3/6)

Read 6 tweets

Bloom Lab

@jbloom_lab

21 Sep

For anyone who doesn't want to do alignments, here are spike amino-acid mutations separating #SARSCoV2 from newly discovered bat CoV BANAL-20-52, which is #SARSCoV2's closest known relative in spike.

Mutations as #SARSCoV2 Wuhan-Hu-1 to BANAL-20-52 in #SARSCoV2 numbering. (1/6)

There are 16 amino-acid substitutions across the 1273-residue spike.

In addition, there is an indel at the furin cleavage site, since like all other known bat sarbecoviruses, BANAL-20-52 lacks the furin cleavage site found in #SARSCoV2. (2/6)

For comparison, Beta and Delta #SARSCoV2 variants each have 7 amino-acid substitutions relative to Wuhan-Hu-1.

So BANAL-20-52 spike about twice as diverged as current #SARSCoV2 variants are from early #SARSCoV2, *plus* of course BANAL-20-52 lacks the furin cleavage site (3/6)

Read 7 tweets

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