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michaelzlin's profile
Michael Lin, MD PhD 🧬
Michael Lin, MD PhD 🧬
Michael Lin, MD PhD  🧬
@michaelzlin

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Michael Lin, MD PhD  🧬

@michaelzlin

Associate Professor of Neurobiology & Bioengineering @Stanford ☘️🧪🦠🧠🌈🔬📖🇺🇲🌏 Molecular engineering for voltage, viruses, and SARSCoV2. Fan of facts.

Harvard/UCLA/HMS/UCSD/Stanford
linlab.stanford.edu
Joined July 2015

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    1. Michael Lin, MD PhD  🧬‏ @michaelzlin 14 Dec 2021

      Now a very important result is that boosted vax is more effective on Delta and Omicron than unboosted recent vax. This is true even for Pfizer where WT neutralization is the same. As the vaccines are made to "WT" sequence, this means boosting is broadening the antibody response!pic.twitter.com/ManEKdCYZX

      10 replies 34 retweets 135 likes
      Show this thread
    2. Michael Lin, MD PhD  🧬‏ @michaelzlin 14 Dec 2021

      Another clear result is that J&J is inferior in all states. You can see across all states in tweet #4, or we can just look at the freshly vaccinated but unboosted state below. The freshly vaxxed state vs WT would reflect the conditions that earned J&J approval originally.pic.twitter.com/PkB6cqqlTW

      1 reply 12 retweets 60 likes
      Show this thread
    3. Michael Lin, MD PhD  🧬‏ @michaelzlin 14 Dec 2021

      Michael Lin, MD PhD  🧬 Retweeted Vivek Naranbhai, MD, PhD, DPhil

      The inferiority of J&J confirms every other comparison study, such as the one below. And we know peak J&J protection for WT was 66% vs >94% for RNA vax. For Delta, it's ~50% (Sisonke), vs 90/85% for Moderna/Pfizer. So nAb levels correlate with outcomes.https://twitter.com/vivek_naranbhai/status/1470292266468130817 …

      Michael Lin, MD PhD  🧬 added,

      Vivek Naranbhai, MD, PhD, DPhil @vivek_naranbhai
      3/ We find a significant hierarchy where Moderna > Pfizer >>>J&J by binding antibodies (spike or RBD, by multiple assays), neutralization of wildtype or variants (incl. delta), and CD4+ T-cells. pic.twitter.com/Oi3uBC0a7M
      Show this thread
      2 replies 10 retweets 47 likes
      Show this thread
    4. Michael Lin, MD PhD  🧬‏ @michaelzlin 14 Dec 2021

      But the most concerning thing is this: J&J+booster doesn't work as well against new variants compared to Moderna+booster or Pfizer+booster. You notice how J&J boosted is similar to Pfizer boosted for WT (especially if high Pfizer outliers removed), but much worse for variants.pic.twitter.com/XDtTPDtvDu

      3 replies 23 retweets 116 likes
      Show this thread
    5. Michael Lin, MD PhD  🧬‏ @michaelzlin 14 Dec 2021

      Michael Lin, MD PhD  🧬 Retweeted Michael Lin, MD PhD  🧬

      Also because of the nice color-coding, we can see above that the JnJers who got Moderna boost (red) were better off than the one who chose a JnJ boost. Small n, but it's as we expect from the heterologous boost study. So can't claim the "wrong" booster.https://twitter.com/michaelzlin/status/1466492316542111749 …

      Michael Lin, MD PhD  🧬 added,

      Michael Lin, MD PhD  🧬 @michaelzlin
      If you compare the green numbers here to 2x Moderna's peak # of 247, you see #JnJers will have higher nAbs after boosting with 1 dose of Pfizer (30mcg) or Moderna 100mcg. The official Moderna booster dose is 50mcg, so likely will be in between the Pfizer and Moderna numbers here. pic.twitter.com/1RiwJaOIWs
      Show this thread
      5 replies 8 retweets 54 likes
      Show this thread
    6. Michael Lin, MD PhD  🧬‏ @michaelzlin 14 Dec 2021

      Pfizer says 3xPfizer gives 70% protection vs Omicron cases. We can then predict boosted Modernans will have the same protection, but boosted JnJers won't.pic.twitter.com/0PNtKVfLGE

      2 replies 13 retweets 56 likes
      Show this thread
    7. Michael Lin, MD PhD  🧬‏ @michaelzlin 14 Dec 2021

      Conclusion: Modernans and Pfizerites are benefiting from a broadening of neutralizing antibody responses after boosting that helps neutralize variants. JnJers don't have the same breadth in their nAbs after boosting. They will be less protected.

      3 replies 14 retweets 76 likes
      Show this thread
    8. Michael Lin, MD PhD  🧬‏ @michaelzlin 14 Dec 2021

      What this suggests is that the initial humoral response elicited by J&J is materially narrower than those elicited by RNA vaccines. As a result the memory B cell expansion induced by boosters results in a broader set of nAbs in Modernans and Pfizerites than JnJers.

      1 reply 8 retweets 54 likes
      Show this thread
    9. Michael Lin, MD PhD  🧬‏ @michaelzlin 14 Dec 2021

      This also means the limited humoral response of the J&J vaccine, long waved aside by Ad proponents who claimed the Ad vaccines had better T cell responses, does indeed lead to a meaningful functional disadvantage.

      5 replies 11 retweets 65 likes
      Show this thread
    10. Michael Lin, MD PhD  🧬‏ @michaelzlin 14 Dec 2021

      Finally what can be done? I think it's pretty clear. JnJers need a RNA vax dose at some point to prime a wide memory B cell population, and then need to be boosted to get the broad antibody response to protect against Delta and Omicron.

      4 replies 22 retweets 96 likes
      Show this thread
      Michael Lin, MD PhD  🧬‏ @michaelzlin 14 Dec 2021

      JnJers who got boosted by Moderna or Pfizer have that RNA dose already. They would benefit greatly from another shot any time after 1 month (based on other studies, 3 months is probably ideal for max response). This "another" shot can be RNA (guaranteed) or could be J&J (below)

      10:22 AM - 14 Dec 2021
      • 36 Retweets
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      19 replies 36 retweets 190 likes
        1. New conversation
        2. Michael Lin, MD PhD  🧬‏ @michaelzlin 14 Dec 2021

          Essentially J&J is not a good way to start a vaccine series when we are faced with variants against which a broad antibody response is useful. Instead a J&J primary vaccine should be considered similar to a natural infection: not enough vs variants.

          2 replies 16 retweets 79 likes
          Show this thread
        3. Michael Lin, MD PhD  🧬‏ @michaelzlin 14 Dec 2021

          JnJers who haven't gotten a RNA booster should be told to get one 2 months after their last J&J, and then another booster 6 months later. They can benefit from the wider B cell repertoire. If they are in a vulnerable population, they absolutely will need it.

          6 replies 21 retweets 91 likes
          Show this thread
        4. Michael Lin, MD PhD  🧬‏ @michaelzlin 14 Dec 2021

          It would makes sense to deprecate J&J to the role of a booster to the RNA vaccines (where it seems to work well enough, see green dot below, and may give a broader CD8 T cell response).pic.twitter.com/UcEXjPKEjW

          4 replies 5 retweets 50 likes
          Show this thread
        5. Michael Lin, MD PhD  🧬‏ @michaelzlin 14 Dec 2021

          Basically you need a RNA vaccine at some time to prime a wide B cell population for antibodies against variants. J&J does not substitute. If you don't do it earlier, you'll just have to do it later. I hope for the health of JnJers that @CDCgov and @CDCDirector will consider it.

          8 replies 25 retweets 129 likes
          Show this thread
        6. Michael Lin, MD PhD  🧬‏ @michaelzlin 14 Dec 2021

          A couple of clarifications: As 2x RNA didn't produce nAbs vs variants (that's the recently vaxxed but unboosted case) but a 3rd shot of any sort did, it means 2x RNA may be needed to activate that broad memory B cell population. So for omicron JnJers may need 2x RNA in sequence.

          10 replies 12 retweets 75 likes
          Show this thread
        7. Michael Lin, MD PhD  🧬‏ @michaelzlin 14 Dec 2021

          Second, J&Jers boosted with Moderna should do fine against Delta. J&J + Moderna gives even more nAbs against Delta than 2x Pfizer unboosted (below), and that correlates with 80% VE against Delta disease. This is consistent with the previous prediction at https://twitter.com/michaelzlin/status/1466488989003616257 …pic.twitter.com/7vW45HFPBi

          4 replies 7 retweets 71 likes
          Show this thread
        8. Michael Lin, MD PhD  🧬‏ @michaelzlin 14 Dec 2021

          So in a sense JJ+RNA booster gets to where 2xRNA was to begin with (pic1 below). But it is worse than 3xRNA for variants, esp Omicron (pic2 below). And with decay we expect some loss of protection to Delta in the upcoming months (if we go by 2xPfizer decay, maybe 50% VE at 6mo).pic.twitter.com/5T7c0F1sDI

          8 replies 9 retweets 74 likes
          Show this thread
        9. Michael Lin, MD PhD  🧬‏ @michaelzlin 14 Dec 2021

          Michael Lin, MD PhD  🧬 Retweeted Michael Lin, MD PhD  🧬

          Made a mistake above regarding J&J as a booster. I misread a case of Moderna+Pfizer (blue dot) as Moderna+JJ (green dot). So this study doesn't say how well J&J works as a boost for RNA vax. The earlier study says J&J is inferior to RNA in boosting nAbshttps://twitter.com/michaelzlin/status/1466488989003616257 …

          Michael Lin, MD PhD  🧬 added,

          Michael Lin, MD PhD  🧬 @michaelzlin
          That's for original strain; for Delta you need ~400. (Not clear for omicron, but expected to be higher than that.) So I circled all the numbers that are ≥400 or are statistically indistinguishable from 400 (close enough). Also translated vaccine names into American English pic.twitter.com/DBIa9LGm8U
          Show this thread
          5 replies 6 retweets 47 likes
          Show this thread
        10. Michael Lin, MD PhD  🧬‏ @michaelzlin 15 Dec 2021

          Another way to explain the data is that 3 immunizations are needed for broad nAbs. Note the infection+2xRNA nAb levels are after 6mo decay; if the sera had been obtained soon after the last shot, those levels might be similar to recent 3xRNA.pic.twitter.com/TK6lNCcQtX

          3 replies 7 retweets 32 likes
          Show this thread
        11. Michael Lin, MD PhD  🧬‏ @michaelzlin 15 Dec 2021

          Since 1xJJ is similar to infection by WT strain (ref below), then we expect that after a second RNA boost (i.e. JJ+RNA+RNA) then nAb levels may be like 3xRNA. So this is even more reason to advocate for a 2nd boost.https://www.nature.com/articles/s41591-021-01377-8 …

          4 replies 15 retweets 66 likes
          Show this thread
        12. Michael Lin, MD PhD  🧬‏ @michaelzlin 15 Dec 2021

          And if we now space the two RNA shots 2-6mo apart then one gets 2-4x higher nAbs than the original 3-4wk interval (https://sciencedirect.com/science/article/pii/S0092867421012216 …). Note the most evasive Beta variant sees the biggest benefit, suggesting activation of a broader set of B cells with the longer interval.pic.twitter.com/caKiW3KBWV

          2 replies 8 retweets 38 likes
          Show this thread
        13. Michael Lin, MD PhD  🧬‏ @michaelzlin 15 Dec 2021

          Above I wrote 3mo as ideal interval in one tweet and 6-mo two tweets later. 3 or 6 mos between RNA shots 2 and 3 elicit similar peak nAbs, based on my skimming of the studies. So anything from 3 to 6 mos would work and timing could be based on when omicron protection needed.

          9 replies 9 retweets 64 likes
          Show this thread
        14. Michael Lin, MD PhD  🧬‏ @michaelzlin 15 Dec 2021

          In sum, 1x J&J is at most like 1 dose of RNA (seen as far back as phase1 antibody measurements). That's been reinforced by its use as a booster where it's worse than 1 dose of RNA. But 1xJ&J and 2xRNA (but not 1xRNA) were designated as vaccinated. This has led to confusion since

          5 replies 9 retweets 59 likes
          Show this thread
        15. Michael Lin, MD PhD  🧬‏ @michaelzlin 15 Dec 2021

          CDC could clarify and rationalize guidance, significantly improving understanding and health, by shifting to a simple counting system. "Make sure you get 3 shots, at most 1 J&J, and space them 2-6 months apart" is all they need to say

          16 replies 58 retweets 222 likes
          Show this thread
        16. Michael Lin, MD PhD  🧬‏ @michaelzlin 16 Dec 2021

          And vulnerable 2xRNA-vaccinated can schedule that 3rd dose before 6mo by declaring themselves immunocompromised. This policy was from back when Pfizer+Moderna's studies found a need, while J&J didn't do studies although JJ was even less protective.https://www.cdc.gov/coronavirus/2019-ncov/vaccines/recommendations/immuno.html …

          4 replies 9 retweets 23 likes
          Show this thread
        17. Michael Lin, MD PhD  🧬‏ @michaelzlin 20 Dec 2021

          Michael Lin, MD PhD  🧬 Retweeted Michael Lin, MD PhD  🧬

          I get asked whether to get 100mcg Moderna (original dose), 50mcg Moderna (booster), or 30mcg Pfizer (original and booster). As mentioned below, you'd expect 100>50>30 in potency since RNA is RNA. But some people asked if diffs in the lipid carriers matter.https://twitter.com/michaelzlin/status/1466492316542111749 …

          Michael Lin, MD PhD  🧬 added,

          Michael Lin, MD PhD  🧬 @michaelzlin
          If you compare the green numbers here to 2x Moderna's peak # of 247, you see #JnJers will have higher nAbs after boosting with 1 dose of Pfizer (30mcg) or Moderna 100mcg. The official Moderna booster dose is 50mcg, so likely will be in between the Pfizer and Moderna numbers here. pic.twitter.com/1RiwJaOIWs
          Show this thread
          4 replies 5 retweets 20 likes
          Show this thread
        18. Michael Lin, MD PhD  🧬‏ @michaelzlin 20 Dec 2021

          Moderna found 100mcg and 50mcg Moderna 3rd doses raise nAb levels against Omicron by 87x and 37x respectively. Pfizer found its 30mcg booster raises nAbs by 25x. The Mod and Pfizer results are in different studies but so far it seems 100>50>30 indeed.https://www.telegraph.co.uk/global-health/science-and-disease/reassuring-moderna-booster-jab-triggers-strong-response-against/ …

          9 replies 16 retweets 49 likes
          Show this thread
        19. Michael Lin, MD PhD  🧬‏ @michaelzlin 27 Dec 2021

          Many are wondering if they can boost earlier than 6mo. The NIH heterologous boost study used 3mo after initial series (1xJJ or 2xRNA). Pfizer tested 8mo after 2xRNA. Results were similar, suggesting 3-8mo all ok. CDC guided 6mo because immunity waned to <50% VE against Delta then

          2 replies 6 retweets 32 likes
          Show this thread
        20. Michael Lin, MD PhD  🧬‏ @michaelzlin 27 Dec 2021

          And now Israel is allowing boosters 3mo after the previous shot. This will allow those 3mo out from last shot to get boosted ahead of winter, whereas earlier you had to wait for 6mos.https://www.usnews.com/news/health-news/articles/2021-12-27/live-updates-israel-trials-4th-dose-of-covid-19-vaccine …

          7 replies 8 retweets 33 likes
          Show this thread
        21. End of conversation

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