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jbloom_lab's profile
Bloom Lab
Bloom Lab
Bloom Lab
@jbloom_lab

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Bloom Lab

@jbloom_lab

Lab studying molecular evolution of proteins and viruses. Affiliated with @fredhutch @HHMINEWS @uwgenome.

Seattle, WA
research.fhcrc.org/bloom/en.html
Joined June 2014

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    1. Bloom Lab‏ @jbloom_lab 25 Nov 2021

      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 https://jbloomlab.github.io/SARS2_RBD_Ab_escape_maps/ … (1/n)

      84 replies 1,261 retweets 2,913 likes
      Show this thread
    2. Bloom Lab‏ @jbloom_lab 25 Nov 2021

      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)pic.twitter.com/YjSifYojIL

      7 replies 170 retweets 571 likes
      Show this thread
    3. Bloom Lab‏ @jbloom_lab 25 Nov 2021

      Another way to assess polyclonal escape is how many epitope classes affected (https://www.nature.com/articles/s41467-021-24435-8 …). 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)

      2 replies 68 retweets 378 likes
      Show this thread
    4. Bloom Lab‏ @jbloom_lab 25 Nov 2021

      Unfortunately, the Nu variant has major escape mutations in each of these three epitope classes, as shown below. (The class 4 epitope less affected, but such antibodies also less potently neutralizing.) (4/n)pic.twitter.com/jBgo8CAdsk

      4 replies 162 retweets 572 likes
      Show this thread
    5. Bloom Lab‏ @jbloom_lab 25 Nov 2021

      Importantly, this does *not* mean Nu variant will fully escape vaccine- or infection-elicited antibodies. @PaulBieniasz @theodora_nyc have shown takes many many mutations to fully escape neutralization (https://www.nature.com/articles/s41586-021-04005-0 …), & there are also T-cells, non-neut Abs, etc. (5/n)

      18 replies 306 retweets 1,028 likes
      Show this thread
      Bloom Lab‏ @jbloom_lab 25 Nov 2021

      But I'd expect the Nu variant to cause more of a hit on vaccine- and infection-elicited antibody neutralization than anything we've seen so far. (6/n)

      2:58 PM - 25 Nov 2021
      • 228 Retweets
      • 877 Likes
      • Linked Out Sue Jackson GuillaumeMichoko G.R.RAO 🇮🇳🇮🇱 Ronen▼ 📍NYC Adrian Bischoff Kay The Masked Jezebel 😷💉 Andrew Macaluso
      6 replies 228 retweets 877 likes
        1. New conversation
        2. Bloom Lab‏ @jbloom_lab 25 Nov 2021

          We can also look at some key monoclonal antibodies. the REGEN-COV cocktail is likely to take a hit for the Nu variant, especially the REGN10987 component. (7/n)pic.twitter.com/iZYGxNZl2o

          2 replies 107 retweets 469 likes
          Show this thread
        3. Bloom Lab‏ @jbloom_lab 25 Nov 2021

          The early Eli Lily antibodies like LY-CoV555 (bamlanivimab) and LY-CoV016, which were already in trouble with current variants, aren't going to do any better against the Nu variant. (8/n)pic.twitter.com/My8GMUDdLa

          3 replies 77 retweets 412 likes
          Show this thread
        4. Bloom Lab‏ @jbloom_lab 25 Nov 2021

          However, it appears the AstraZeneca AZD7442 cocktail and Vir's S309 are likely to hold up better against the Nu variant. See below. (9/n)pic.twitter.com/PNlJjHc5fT

          10 replies 204 retweets 764 likes
          Show this thread
        5. Bloom Lab‏ @jbloom_lab 25 Nov 2021

          You can explore other antibodies that might be of interest to you at https://jbloomlab.github.io/SARS2_RBD_Ab_escape_maps/ …. Importantly, all above results from high-throughput deep mutational scanning, and need to be validated in traditional experiments for high confidence. (10/n)

          3 replies 71 retweets 394 likes
          Show this thread
        6. Bloom Lab‏ @jbloom_lab 25 Nov 2021

          Bloom Lab Retweeted Tulio de Oliveira

          Also note large antigenic change does not mean Nu will necessarily spread & outcompete other variants. That will also depend on its transmissibility, which has been discussed by @Tuliodna & others (eg, https://twitter.com/Tuliodna/status/1463911571176968194 …) and for which data remains preliminary. (11/n)

          Bloom Lab added,

          Tulio de Oliveira @Tuliodna
          This new variant, B.1.1.529 seems to spread very quick! In less than 2 weeks now dominates all infections following a devastating Delta wave in South Africa (Blue new variant, now at 75% of last genomes and soon to reach 100%) pic.twitter.com/Z9mde45Qe0
          Show this thread
          7 replies 130 retweets 510 likes
          Show this thread
        7. Bloom Lab‏ @jbloom_lab 25 Nov 2021

          Bloom Lab Retweeted Trevor Bedford

          As @trvrb discussed in excellent recent thread, selection on variants so far may be dominated more by transmissibility than antigenic selection (https://twitter.com/trvrb/status/1462816217794695170 …). But I'm not as sanguine that antigenic selection isn't also playing substantial role... (12/n)

          Bloom Lab added,

          Trevor BedfordVerified account @trvrb
          Did vaccination drive the evolution of variant (Alpha, Beta, etc...) SARS-CoV-2 viruses? This is a legitimate scientific question, but after looking into it I don't believe this to be the case. 1/19
          Show this thread
          3 replies 83 retweets 432 likes
          Show this thread
        8. Bloom Lab‏ @jbloom_lab 25 Nov 2021

          Bloom Lab Retweeted Bloom Lab

          Reason I say that is comparison of Nu variant to BANAL-20-52, a SARS-related CoV isolated from bats. If we compare both BANAL-20-52 and Nu to Wuhan-Hu-1, Nu has *many* more mutations that strongly affect antigenicity (https://twitter.com/jbloom_lab/status/1440309655087902720 …). (13/n)

          Bloom Lab added,

          Bloom Lab @jbloom_lab
          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) pic.twitter.com/RsplDQmbt8
          Show this thread
          3 replies 70 retweets 276 likes
          Show this thread
        9. Bloom Lab‏ @jbloom_lab 25 Nov 2021

          If selection was mostly for transmissibility, I'd expect sites of divergence of Nu and BANAL-20-52 relative to Wuhan-Hu-1 to perhaps be similarly distributed with respect to antigenic sites. But instead, Nu mutations much more focused in major antigenic sites. (14/n)

          4 replies 60 retweets 302 likes
          Show this thread
        10. Bloom Lab‏ @jbloom_lab 25 Nov 2021

          Bloom Lab Retweeted Bloom Lab

          We can also use deep mutational scanning to assess how mutations in Nu affect ACE2 affinity (https://twitter.com/jbloom_lab/status/1463879246875529224 …). But I suspect works less well than for antigenic mutations discussed above as there's lot more mutational epistasis for ACE2 affinity (eg, N501 & Q498). (15/n)

          Bloom Lab added,

          Bloom Lab @jbloom_lab
          Replying to @florian_krammer
          I'd be shocked if it doesn't bind ACE2. Third of mutations in B.1.1.529 RBD enhance ACE2 affinity in Wuhan-Hu-1 (https://jbloomlab.github.io/SARS-CoV-2-RBD_DMS/ …). We also think (cc @tylernstarr @AllieGreaney) there's favorable epistasis among some mutations that individually decrease affinity in Wuhan-1 pic.twitter.com/MqnBkxpmmU
          2 replies 45 retweets 213 likes
          Show this thread
        11. Bloom Lab‏ @jbloom_lab 25 Nov 2021

          Important caveat: all of above is based on deep mutational scanning experiments. I'm sure more Nu-specific data will emerge in coming weeks to months. But I think it's useful to use prospective data we already have to calibrate what to expect. (16/n)

          3 replies 49 retweets 307 likes
          Show this thread
        12. Bloom Lab‏ @jbloom_lab 25 Nov 2021

          Bloom Lab Retweeted Tulio de Oliveira

          Thanks to @AllieGreaney @tylernstarr for doing deep mutational scanning on which above is predicated, & @NussenzweigL @VUMC_Vaccines @seth_zost @Vir_Biotech for sharing the antibodies. And of course the scientists providing rapid information about Nu (https://twitter.com/Tuliodna/status/1463911554538160130 …).

          Bloom Lab added,

          Tulio de Oliveira @Tuliodna
          Busy day on B.1.1.529 - a variant of great concern - The world should provide support to South Africa and Africa and not discriminate or isolate it! By protecting and supporting it, we will protect the world! A plea for billionaires and financial institutions. 1/8 tweets
          Show this thread
          11 replies 61 retweets 336 likes
          Show this thread
        13. Bloom Lab‏ @jbloom_lab 25 Nov 2021

          Bloom Lab Retweeted Theo Sanderson

          And probably I should have used the variant name B.1.1.529 throughout above thread...https://twitter.com/theosanderson/status/1464007031174619143 …

          Bloom Lab added,

          Theo Sanderson @theosanderson
          Funny that Twitter seems to have named it Nu without any need for the WHO to get involved! (I'd assumed they'd skip nu but seems unlikely now)
          13 replies 45 retweets 285 likes
          Show this thread
        14. Bloom Lab‏ @jbloom_lab 26 Nov 2021

          Bloom Lab Retweeted Bloom Lab

          For people interested in G446 mutations, I'm going to link back to some details on this site. Here is an old thread discussing how G446 is a major site of escape in the class 3 epitope where (as of March 2021) mutations were not prevalent:https://twitter.com/jbloom_lab/status/1372669322657550337 …

          Bloom Lab added,

          Bloom Lab @jbloom_lab
          We analyzed which antibody classes escaped by emerging #SARSCoV2 mutations. Mutations spreading at sites of biggest escape for class 1 (K417) & class 2 (E484). But mutations at major class 3 escape sites (K444, G446, G447) not common, although L452 is modest class 3 escape (7/n) pic.twitter.com/DIRnv7Tl97
          Show this thread
          1 reply 17 retweets 75 likes
          Show this thread
        15. Bloom Lab‏ @jbloom_lab 26 Nov 2021

          Bloom Lab Retweeted Bloom Lab

          Also, here are old data showing how for a minority of convalescent individuals, the epitope centered on G446 is immunodominant with respect to serum neutralization:https://twitter.com/jbloom_lab/status/1359136451875598345 …

          Bloom Lab added,

          Bloom Lab @jbloom_lab
          Indeed, for minority of people, mutations in 443-450 loop (eg, at G446 as below https://twitter.com/jbloom_lab/status/1346442020051537922 …) already have bigger effect than E484K. And if E484 epitope is ablated as E484K spreads, I'd expect 443-450 loop to take on growing importance for remaining immunity. (6/n)
          Show this thread
          1 reply 12 retweets 71 likes
          Show this thread
        16. Bloom Lab‏ @jbloom_lab 26 Nov 2021

          Also, checkout the awesome CoV-RDB database of Bob Shafer, @Philip_Tzou, @sergeilkp, K Tao which compiles experimental data on G446 (and also whatever other mutation you care about): https://covdb.stanford.edu/search-drdb/?host=human&position=S%3A446 …

          1 reply 11 retweets 70 likes
          Show this thread
        17. Bloom Lab‏ @jbloom_lab 26 Nov 2021

          Here are data from one of @AllieGreaney's papers (Fig 5 of https://www.science.org/doi/10.1126/scitranslmed.abi9915 …) showing that a K417-G446-E484 triple mutant sometimes but not always fully escapes neutralization by RBD-targeted antibodies, and effect is worse for convalescent than mRNA-1273 vaccine sera.pic.twitter.com/rtdbwS7QQ7

          5 replies 45 retweets 150 likes
          Show this thread
        18. Bloom Lab‏ @jbloom_lab 26 Nov 2021

          Bloom Lab Retweeted Theodora

          Also adding this as another highly informed view just for balance on question of possible extent of antibody neutralization escape:https://twitter.com/theodora_nyc/status/1464257411582148608 …

          Bloom Lab added,

          Theodora @theodora_nyc
          I wish I was as optimistic @jbloom_lab Our polymutant spike has 20 aa substitutions and is almost completely resistant to neutralization by almost all vaccinated and convalescent plasma we tested. This new one has more in overlapping regions. https://twitter.com/jbloom_lab/status/1464005690775654401 …
          Show this thread
          9 replies 23 retweets 128 likes
          Show this thread
        19. End of conversation

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