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Clinical Trials

More Pfizer/BioNTech Data On Their Actual Vaccine Candidate

When we last heard from the Pfizer/BioNTech vaccine program, they had picked a different candidate than the one that they had already published on (BNT162b1). Today they’ve released more data about the actual candidate, BNT162b2. And it seems pretty clear why they went with it.

This preprint describes a head-to-head study (NCT04368728) between their two candidates, in a rather wide-ranging trial with 13 different treatment groups varying by the age of the volunteers (18-55 or 65-85) and the vaccine dose (10, 20, or 30 micrograms, each in two doses 21 days apart, with one group getting a single 100 microgram shot). Each group had 12 people dosed with a vaccine candidate and 3 placebo controls.

Overall, the “b2” vaccine produced fewer reactions on injection, and milder systemic reactions such as fever, body ache, etc. Older patients tended to have less reaction than younger ones, with both candidates. This is something to keep in mind – the other day, I was wondering if the mild reactions to the SinoPharm inactivated virus vaccine might indicate that it was raising less of a response, but that is clearly not always the case (I’ve updated that earlier post with a link to this one as well).

The antibody response in the two vaccines was quite similar, and they both showed the same trends (for example, lower neutralizing antibody response in the older patients, one-third to one-half, which will be something watch for when we get efficacy data). The booster shot was definitely needed – antibody titers were far better after the second injection. And while the 20 microgram dose was definitely better than the 10, the 30 microgram dose was slightly better in some groups but not in others. The Phase III, though, will be two doses of the 30 microgram, since it also had no worse safety signals.

The difference between the two candidates is that the b1 vaccine encodes the RBD of the Spike domain, presented as a trimer, while the b2 is the full-length Spike with a few mutations to make it more stable. The b1 therefore has more actual RNA molecules in it than the b2, but the lipid nanoparticle formulation is the same. The paper notes that it’s not clear why the b2 candidate has significantly fewer side effects – the number of RNAs could be part of it, but these effects are also known to depend on the particular RNA sequences involved, so who knows? The authors also mention that they expect a wider variety of T-cell responses from the full-length antigen in the b2 vaccine, but that this study did not include T-cell characterization. Pfizer’s own comments lead one to believe that this is what they’re seeing, but was that based on data or on expectations? At any rate, they say that this will be reported separately, and I look forward to seeing it.

But what I look forward to the most is seeing how all of these Phase I profiles translate to the real world of protection from the damned coronavirus. We’re going to learn more about immunological correlates more quickly than we have ever learned for any pathogen before. There are so many different platforms in trials now, each with their differences, and we will be getting piles of data in rapid succession from trials of tens of thousands of people all over the world. No one would have ever set up such a gigantic experimental landscape under non-emergency conditions; from the clinical perspective it’s an unprecedented immunological Woodstock.

And we’re going to have to get prepared for it. There are several believable outcomes (good, bad, and just plain mixed) that I don’t think that the general public has anticipated, and those will be the subject of a coming post!

105 comments on “More Pfizer/BioNTech Data On Their Actual Vaccine Candidate”

  1. Dr. Manhattan says:

    “ immunological Woodstock.”. I like that phrase. Keeping with that theme, here’s hoping that at the end of all these various vaccine trials, we will end up with plenty of Grateful Undead.

    1. Another Guy says:

      Or hopefully the “Grateful Not-Dead”. The undead are scary.

      1. Hap says:

        I’m hoping for a lot of “dead” or nonexistent virus, though.

        1. Alan says:

          Winter is coming.

    2. Clifford Orchard says:

      Absolutely up there with ‘ceiling tile remover’ as one of the highlights of this blog

      1. Anonymous says:

        link? 🙂

      2. Simon Auclair the Great and Terrible says:

        No, Crater Bait is the best.

        1. Silverlake Bodhisattva says:

          Gonna have to put in a vote for “shrapneliferousness”.

    3. loupgarous says:

      And no “brown acid” bad trips.

  2. sgcox says:

    I might look stupid but I really do not understand how RBD only vaccine works.
    Ok, mRNA produces trimeric RBD in transfected cells, than what ? Does it get chopped up and presented as peptides by HLA ? Get secreted and recognised by B-lymphocytes ?
    The full length Spike with TMH should get epitope exposed on the cell surface and raise immune response, I can see that, but RBD alone ?

    1. Barry says:

      Yes, the wager is that fragments of the RBD will be displayed on MHC and will provoke T-cell response there. The cell that took up the mRNA vaccine will be sacrificed to prime the immune response.

    2. Toni says:

      I’m not quite sure if I understood your question correctly.
      The antigen is not only cleaved into peptides which are presented to T cells by APCs (probably via class I MHC), it must also be recognized as a more or less intact antigen (“Get secreted and recognised by B-lymphocytes ?”) by B cells via the B cell receptor (i.e. by the still immature antibody) and then transferred to MHC-II of the B-cell. This MHC-peptide-TCR contact (and other signals) initiates the maturation of the matching B cells.

      1. gcc says:

        I think sgcox was assuming that the trimeric RBD is expressed just as an intracellular protein (rather than a secreted protein), leading to the question of how the intact protein would gain access to the B cell receptors. I know antibodies *can* develop against intracellular proteins (for example, in autoimmune diseases), but I wouldn’t think expressing a foreign protein in the cytoplasm would be an efficient way to trigger a B cell response. Maybe the RBD vaccine construct expresses a secreted form? It’s a bit of a moot point anyway since they’re going with the full-length spike version for the Phase III trial, but I was wondering about this as well.

  3. Matthew says:

    It’s somewhat reassuring to have a large, global partnership of Pfizer/BioNTech making decent progress on this effort. They have the experience and resources to see this through.

  4. Michael says:

    >>Pfizer’s own comments lead one to believe that this is what they’re seeing, but was that based on data or on expectations? At any rate, they say that this will be reported separately, and I look forward to seeing it.

    Derek, it appears to be based on data. The article published in Nature on the b1 candidate stated that a manuscript on the b2 candidate was in the works, and here’s the citation at footnote 24:

    “Sahin et al. 2020, Concurrent antibody and T cell responses in a COVID-19 vaccine, manuscript in preparation.”

  5. Nick says:

    Forgive me, I’m just a process chemist so this isn’t my field: I’ve been wondering, given the pre-print out of Wuhan indicating that the IgG-RBD-S antibody is likely the best neutralization spot ( would there be a benefit to using the b2 as the prime vaccination, then the b1 RBD encoding RNA as the booster? It seems that something that would induce the general T-cell response against the spike protein, then enhance the RBD response would be preferential.

    It would obviously be a bigger problem on scale-up there, I’m less familiar with RNA scale-up techniques so I don’t know how difficult that would actually be.

  6. Bryon Wasserman says:

    These are also the first results we’ve seen for older people (65+)? Seems exciting and notable that they were able to produce an antibody response.

    1. Duncan says:

      I’m a layman, so sorry if this is a silly question.

      In terms of the age profile I think that it is reasonably clear that risk increases with age and therefore priority for vaccines would be given to the elder (and most particularly those with underlying conditions). I think that most people are adult enough to understand that this vaccine will be made available on a priority basis. And also that the ‘better’ products would go to those prioritised.

      But would there ever be a point where people would NOT be vaccinated until a certain age, unless there were some other reason? In the UK children are not routinely vaccinated for chicken pox and I was one of the very few people who had never had it. I understand that generally the chicken pox vaccine is only available in the UK for people above a certain age in the mid 30s and who need to be vaccinated. Is it possible that covid might end up like this?

      And as an aside – I took the chicken pox vaccine then six weeks later I walked into an infant school where there was a chicken pox outbreak. I was fine.

      1. David says:

        Vaccination against chickenpox is standard in the US. In the UK there appear to be concerns about whether vaccination-induced immunity fades in adulthood and whether having a pool of unvaccinated children effectively provides a booster to nearby adults. I’m not a virologist or epidemiologist, but these arguments have never made much sense to me. This european consensus paper is pretty good, though a bit old: Pediatr Infect Dis J 2004 v23(5):379-89.

      2. AVS-600 says:

        I’m by no means a policy expert, so take this with a grain of salt, but the big difference between chickenpox and covid is that most adults already have what is essentially sterilizing immunity to chickenpox (with a caveat, as noted below: the virus still exists in the body and just doesn’t do anything most of the time). Furthermore, it’s well understood that exposure to chickenpox provides that lifelong immunity.

        In contrast, it’s unclear (and realistically, will remain unclear for longer than it’s important) whether people who get covid actually provoke a strong enough immune response to provide long-term immunity, especially in circumstances where the disease is mild or asymptomatic (which it is in most children). So while it makes sense that children would be lower-priority while the vaccine supply is scarce, it probably doesn’t make sense not to vaccinate them at all.

        (As an aside, if I lived in the UK I would be pretty annoyed to be forced to get chickenpox immunity the old-fashioned way; from what I understand, shingles isn’t any fun at all).

        1. KazooChemist says:

          Been there, done that. I had what was a “mild” case of shingles on my chest, shoulders, and down one arm. It was excruciatingly painful. A single sheet touching my chest was over the top painful. I was one of the unfortunate individuals who proved the statistics that the first “shingles” vaccine did not protect everyone. I have received the newer vaccine and hope that it will protect me. Trust me! Get vaccinated!

  7. David G Whiteis says:

    In terms of priority — there is a contrarian opinion (which might be growing) that maybe the younger and healthier should actually be vaccinated first, because they’re the ones with the most robust immune systems, thus they’re the ones for whom the vaccine is likely to be most effective. They’re also more likely to be socially active (i.e., at risk for being in “superspreader” situations). If they were immunized first, they’d be less likely to spread the virus to the older and more vulnerable.

    In terms of not vaccinating people under 30 at all, that seems to me a very bad idea. Even if they’re less likely to die from the disease, the morbidities associated with “surviving” it can be quite severe. And, as we’ve seen, outbreaks among young adults and adolescents are a significant reason for recent spikes in many U.S. states.

    As for chicken pox — that’s an interesting one to consider in this context. The varicella zoster zoster virus that causes chicken pox remains dormant in the body after one has “recovered” from it — it can re-emerge later, in adulthood, as herpes zoster (a.k.a. “shingles”). Since I’m also a layman, I don’t know whether any other viruses have this capacity to come back as “something else” years later, but if so, it’s a rather daunting thing to consider in terms of COVID.

    1. Bryon says:

      We don’t know for sure that the vaccine will prevent infection and transmission. It may just affect disease severity. I think that if we have a limited supply the focus will be on protecting the people most at risk of dying or suffering from severe disease rather than going through some kind of indirect bank shot. I think that people in public-facing jobs may also get higher priority.

      1. Lamont says:

        We know that neutralizing antibody titers appear to be protective in humans based on the high attack rate fishing vessel study. We know vaccines produce high neutralizing antibody titers in humans. We also know SARS-CoV-2 disease protects against rechallenge in monkeys and that vaccination with the ChAdOx1 vaccine protects against virus replication in the lungs of monkeys. At this point qualifying that we haven’t proven that vaccines protect humans against infection seems overly cautious. We still need to do the Phase 3 trials to figure out which ones have the best protection-vs-safety profile and weigh that against which ones can be produced the fastest, but the uncertainties over vaccines being protective against infection have narrowed dramatically and are converting on that they are protective against infection.

        1. Lamont says:


        2. Barry says:

          Neutralizing antibodies (IgG) in the plasma correlate with non-infection under what look like pretty severe (albeit uncontrolled) challenge on the fishing boat. But those IgG probably come with T-cells, and IgA, (and IgM) A good vaccine would elicit all of those, and should provide protection. Convalescent plasma therapy delivers the IgG and IgA (and IgM?) w/o the T-cells and still seems promising. But just administering mAbs (if by mAbs we mean IgG) or nanoBodies may still be a stretch too far. These are still very much in the ‘Research’ phase, and not ‘Development’.

        3. David G Whiteis says:

          And, of course, we need to at least try to assess the extent to which different populations at different levels of risk (e.g., the elderly; maybe also the obese) will be protected, and — of course — the duration of the protection.

          Which leads me to another layman’s question: The plan right now is that if one (or more) of the vaccines now in Phase III trials proves effective and safe, it/they will be rolled out within a few months This means that we won’t really know for at least the next six or twelve months whether any immunity it provides will be lasting. Will vaccinated people have to keep coming back for testing, to ensure that their immunity is still robust? That sounds like a logistical impossibiilty. Or are we jsut going to have to wait for a new flare-up six or twelve months down the road, get dragged back into this nightmare, start all over again?

          1. An Old Chemist says:

            Eric Topol
            Today’s “breakthrough” announcement is unlikely to be any breakthrough.
            1. Convalescent plasma has no randomized trials. It contains many antibodies that have no neutralizing effect. If it has efficacy, it will be be relatively modest, at best.

        4. KazooChemist says:

          Sorry to bring this up, Lamont. I am not specifically questioning your post (I agree with it). However, the fishing boat report was not a randomly assigned, double blinded, pre-ordained endpoints type of trial. Everyone seems on a tripwire to dismiss any and all retrospective studies, especially when they do not fit their own biases. I think we needed a fleet of fishing boats, crewed by a broad spectrum of age and ethnic groups, some seeded with coronavirus positive seamen and some sterilized before leaving port. Only then will the fishing boat anecdote have any impact.

      2. Alia says:

        I am teacher, scheduled to go back to school in September (unless our government changes their mind at the last moment, which they are prone to do) and I do hope we would get the vaccine quite early.

        1. Alia agreed better to have than not have. I am currently in the program However we must both be aware that there are so many unknowns. Best case, you will have immunity for rest of your life, worst case a reduction in symptoms for a couple of months, but we can still get sick and infect other people. Everyone’s response will be different. But I am hopping this is the best one. If not, we may have to get another companies vaccine when it becomes available. That is just like I am doing now for the Shingles. The first one only had about 50% effectiveness and did not last. My fingers crossed.

    2. Oudeis says:

      I’m a layman, too, but it’s my understanding that measles can do something like what you’re describing, with devastating effect:

      I don’t know how many other viruses do this kind of thing.

  8. TallDave says:

    was a bit shocked to hear Moderna was having trouble finding volunteers for theirs

    suggests the market may be limited to the margins, particularly if death rates fall off dramatically by the time they’re widely available

    perhaps this is optimistic but guesstimating synthetic antibody cocktails will achieve 90% to 99% efficacy (i.e. something like 10-100 adverse events in control group for every such event in the dosed group)… that might effectively end the pandemic, once production can ramp up to levels where treating contacts is feasible (e.g. Roche just signed a deal with Regeneron)… hope we get data soon, some expected next month

    1. Marko says:

      How much are they going to cost ? If the cocktail costs $10k , or even $1k , per dose , it might effectively end the pandemic for the few , but it won’t for the masses.

      If they could price it like a vaccine it might work , but you’d still sacrifice the potential for long-term protection.

      1. David G Whiteis says:

        Some governments, e.g., Australia’s, are promising that the vaccine will be free to all citizens. In the U.S., the “official” line is that it’s “likely” to be free for most people, but — as usual — the details are murky and confusing:

      2. TallDave says:

        according to the publicly announced contracts maybe $300 to the Feds

        free for everyone else

        1. Moderna have quoted $39 per dose (which squares with US supply agreements), and cite a third party “fair value” estimate of $300 for all adults, and more that $700 in high-risk populations. BioNTech/Pfizer and J&J are looking at $4 to $10 per dose.

          1. TallDave says:

            those are vaccines, not synthetic antibodies

      3. TallDave says:

        but yes the long term question is interesting… if there’s an animal reservoir we might have to expect periodic re-eruptions

        1. Marko says:

          If the cocktail is free to the public in the US then I can see how it could have a major impact if it has the efficacy you suggest. However , you don’t need animal reservoirs to provide the source for future outbreaks. There’s no way those cocktails will reach the entirety of the global population in the foreseeable future. One plane flight or refugee inflow is all it would take to spark a new outbreak. You’d still need a vaccine to ( hopefully ) give you some protection over the long haul.

          1. TallDave says:

            or one lab leak 🙂

            otoh by 2022 there will likely be a half-dozen COVID antibody cocktails available globally, and who knows how many vaccines… it only survives in untreated humans a month or two at most so odds seem good we can eventually stamp it out entirely in humans

            of course if you already have the cure the outbreaks are also quite a bit less concerning

      4. John Hasler says:

        Cost or price? If it *costs* $10k relatively few are likely to get it no matter who pays.

    2. David G Whiteis says:

      From where does that 90 – 99% figure derive? No one, not even the most optimistic “Operation Warp Speed” shills, are going that high in their estimates. Anthony Fauci seems to think that 75% is the high-end estimate, and that somewhere between 50 60% is closer to what we’ll actually see.

      1. TallDave says:

        lol well since I just invented that metric in my head a little bit ago I seriously doubt anyone else has weighed in on it

        my guesstimate is based on the animal studies

        source for your claim?

        1. TallDave says:

          ah, I see your confusion now — those were the vaccination numbers… as best I can tell Fauci has never offered any quantitative assessment of synthetic antibodies (but has voiced considerable enthusiasm, for whatever that’s worth)

        2. TallDave says:


          Fauci, the top U.S. infectious disease expert, described them as “precise bullets” that can be developed from antibodies from other people who’ve been infected and used as a treatment to fight the virus at multiple stages.

          “What we really need are drugs that, when given early, can prevent a symptomatic person from requiring hospitalization or very dramatically diminish the time that they’re symptomatic,” Fauci said during the Facebook Live interview on Thursday.

          1. David G Whiteis says:

            Okay, I apologize — we seem to have been seesawing between discussing the vaccines currently in Phase II / III trials (spurred by the original topic of this discussion, which was the Pfizer/BioNTech vaccine) , and the possible advantages of a neutralizing antibody serum. I guess I got seesaw’d — Sorry!

    3. MagickChicken says:

      It has to do with their history. No therapeutics brought successfully to market (or even Phase III), and a reputation as an investment platform rather than a drug company.

      The mRNA platform might concern some as well, but Pfizer doesn’t seem to have had any issue (I volunteered for Pfizer’s, but not Moderna’s).

      1. David G Whiteis says:

        Also, whether it’s fair or not, there’s the perception of unsavory political/financial conflicts of interest with Trump’s “Operation Warp Speed.” Moncef Slaoui was a major Moderna investor; only under pressure did he sell his stock after he was appointed to head up the “Warp Speed” initiative.

        For that matter, though, Slaoui was the head of head of GlaxoSmithKline’s vaccines department for many years — and GSK recently signed onto a $2 billion Operation Warp Speed contract along with Sanofi. So we’ll see what kind of distrust arises surrounding THAT deal.

  9. Blaine White, M.D. says:

    Does anyone know if diabetes affects glycosylation of Fc on IgG? This molecular modification looks like a basis of the “macrophage activation syndrome” that actually kills Covid-19 patients. For context of this question see Hoepel W et al. Anti-SARS-CoV-2 IgG from severely ill Covid-19 patients promotes macrophage hyper-inflammatory responses. BioRxiv 2020; doi:

    Although not yet near even Phase 1 trial, an alternate vaccine approach is to directly target T-cell immunity with immunizing epitopes of multiple viral proteins. See Gauttier V et al. Tissue-resident memory CD8 T-cell responses elicited by a single injection of a multi-target COVID-19 vaccine. BioRxiv 2020; doi: This would eliminate viral escape from our immunity by just mutations of 1 protein (Spike), and multi-epitope T-cell immunity should be long lasting.

    Thinking about ways around things that could go wrong with making IgG against just Spike motifs.

  10. Phil says:

    So, this is kinda a nightmare hypothesis, but please bear with me. The b2 candidate encodes “the full-length Spike with a few mutations to make it more stable”. The one interesting in-the-field mutation that’s been observed as the epidemic has progressed has been D614G – a mutation in the Spike protein that makes it more stable, and the resulting virus seemingly more infectious in aggregate. What is the risk of someone with an active infection receiving this vaccine, and consequently recombining the vaccine RNA into live virus, that then transmits?

    What’s the balance of risk between chancing this possibility to roll out the vaccine as rapidly as possible, and screening against active infection at the time of administration?

    1. sgcox says:

      In today Cell:
      “the global expansion of G614 whether through natural selection or chance means that this variant now is the pandemic.”
      I guess it is close to 99% prevalence in Europe and US. Too late to worry about recombination.

    2. gcc says:

      I believe the mutations introduced into the spike gene in the vaccine don’t just generally increase the stability of the protein, but specifically stabilize the protein in the prefusion conformation. Even if these mutations somehow got into a complete virus, they would be expected to reduce fusion of the virus with cells and therefore reduce infectivity (rather than increase it as Phil suggested).

  11. debinski says:

    I am thrilled to see this data come out having received a vaccine in the Pfizer trial on Tuesday. I was totally convinced I got placebo because I had 0 side effects, not even a sore arm. But looking at the data in the >65 yo group, only about 75% got pain at injection site and no one got a fever on first injection. Less than 50% got other systemic effects. Holding out hope I didn’t get placebo.

    1. Sam says:

      Yes I am also in the Pfizer phase III and it drives me crazy to think I got placebo….lol

  12. Marko says:

    Russia to begin COVID-19 vaccine trials on 40,000 people next week

  13. MFruchtman says:

    J&J have decided to go with their one jab dosing in their Phase 3 trial against COVID-19. Starting date around September 5. That is one hell of catchup in speed from where they started compared to Pfizer, AstraZeneca, and Moderna.

    Participants will receive intramuscular (IM) injection of Ad26.COV2.S at a dose level of 1^10*11 virus particles (vp) as single dose vaccine on Day 1.

    1. Marko says:

      Also interesting that they’re aiming for an enrollment of up to 60k , and their primary outcome measure is reduction in moderate-to-severe disease , as opposed to a reduction in rates of infection.

      1. David G Whiteis says:

        I don’t remember who it was, now, but a spokesperson for either the FDA or CDC said that a vaccine that eased symptoms but did not prevent infection would be basically “creating asymptomatic carriers,” so approval would be unlikely.

        1. Marko says:

          This sounds like your Chicago health official “quote”.

          If there’s no link , it didn’t happen , t least as far as I’m concerned.

          1. David G Whiteis says:

            Okay, it was a joint interveiew with Peter Marks (FDA), Paul Offit, and Leonard Friedland (GlaxoSmithKline). I had remembered the the quote as being from Marks, but it was actually from Friedland:
            Q: If a vaccine doesn’t actually prevent disease but just reduces its severity, that’s still helpful, right?
            A: “Perhaps. But it could inadvertently boost risk of transmission. If you have a vaccine that essentially just creates more asymptomatic carriers, we’d have to look very closely about whether that is a safe vaccine to deploy.”
            Here’s the link:

          2. Marko says:

            A bit of difference between what you claimed he said : “approval would be unlikely” , and what he actually said. It’s also contrary to the FDA guidance that was explicitly provided very early in the process :

            “….the FDA would expect that a COVID-19 vaccine would prevent disease or decrease its severity in at least 50% of people who are vaccinated. ”


            Do you actually think J&J would choose a primary endpoint that , once reached , would likely be rejected by the FDA ?

            I don’t have much doubt that any vaccine approved will reduce infection rates. I do question how long they will do so. If sterilizing immunity wanes after several months , but protection against severe disease outcomes is more durable , I suspect the FDA would view that “disease endpoint” quite favorably.The J&J trial is sized and designed to be able to make that determination.

  14. Blaine White, M.D. says:

    I asked yesterday if anyone knew anything about IgG Fc glycosylation and diabetes. With a bit more literature digging, the answer is yes, although the data is only recently emerging, and the particulars of the biochemistry are complex. The Fc glycosylation pattern seems to be shifted toward a more proinflamatory phenotype in both Type 1 and Type 2 diabetes ( and DOI: 10.1089/omi.2019.0052). Elevated HbA1c (a glycosylated form of hemoglobin used clinically as an indicator of chronic glucose elevation) appears to be associated with this shift in the Fc glycosylation pattern.

    We know from essentially all clinical studies of Covid-19 infections that diabetes is a major risk factor for serious lung pathology. Taken together with the very recent evidence from Hoepel et al (, this suggests very cautious and patient Phase 3 trial evaluation in Type 1 and Type 2 diabetic patients of all vaccines targeting the Covid-19 Spike protein for induction of IgG immunity.

  15. Josh says:

    Has anyone seen a statistical plan for the phase II/III COVID vaccine studies? Will they do an interim analysis after a certain number of events (eg positive molecular tests for SARS-CoV-2) or after a certain fraction of the expected subjects are enrolled? They can’t possibly be planning to wait until the last time point is reached, which would be up to two years.

  16. DrivingAway, before the Elders awaken says:


    Still waiting for Derek to write “Diseases I won’t work with”
    —- In short story form, perhaps as a movie script.
    I suggest the title “Bat Plagues of Doom, Chthulu’s Revenge.”

    1. loupgarous says:

      Since Derek’s a medicinal chemist, it’s much more likely he’d give us “”Biotoxins I Won’t Work With” as a chapter in “TIWWW – the Book” (most of that chapter’s already written.)

  17. Ramkrishna Reddy Vakiti says:

    Latest article for activity against SARS-CoV-2

    GRL-0920, an Indole Chloropyridinyl Ester, Completely Blocks SARS-CoV-2 Infection

    1. Driiive, said the green monkey says:

      Vero E6 cells. Derek and others have pointed out that these have (some sort of) biological pathway difference in the chain of SARS-2 activity compared to human cells, human epithelial in particular. The diff is significant enough that X which works with VeroE6 may fail completely in humans.
      That’s all I know, for more than that you’ll need to ask an akshully biologist.

    2. drsnowboard says:

      In vitro study of an activated ester required for Cys acylation does not take us much closer to a therapeutic. Chemical stability, plasma stability?

    3. sgcox says:

      I opened PDF, looked on Fig.2, closed my mouth and sent the paper to trash bin.

    4. An Old Chemist says:

      This is an Arun k. Ghosh discovery! Arun Ghosh is the inventor of an AIDS drug, Darunavir, named after him. He also discovered a few highly potent compounds against SARS.

  18. Ted says:

    If they are confident that BNT162b2 is the better candidate, why did they just decide to start a new trial in China with BNT162b1 (and not BNT162b2)?

    1. COVIDiot 19 says:

      Always have a backup for if the first one fails.

  19. Marko says:

    Sounds like the big Trump announcement today will be that the FDA has granted an EUA for convalescent plasma :

    1. Marko says:

      Here it is :

      I’d expect an EUA for a vaccine before Nov. 3 as well , safety and the resignation of public heath officials be damned. There’s an election to be won.

      1. Driving, in circles says:

        I’m hoping for an early announcement (to address the public’s fear) and a slow rollout to selected groups, basically a large phase 3 by another name.

        1. David G Whiteis says:

          Wouldn’t an early announcement simply exacerbate the public’s fears? I think it’s safe to say that conflicting (and, often, blatantly untrue) statements from the White House have already set a very bad tone; even the term “Operation Warp Speed” is seriously misguided, I believe, making the attempts to develop and test a vaccine sound like a rush job instead of a legitimate medical /scientific enterprise. I’m afraid that an early approval would simply exacerbate this distrust, probably fatally.

          It’s also undeniable, whether or not everyone likes it, that for as long as Donald Trump is President, response in the African-American community,, and most likely the Hispanic community as well, will almost certainly be tepid at best. Any vaccine that gets approved under his watch will be “claimed” by him as a victory — an immediate, probably fatal blow to its acceptance in communities that have come to perceive him as virtually an existential enemy. It’s an unfortunate fact that to be truly effective among the populations that need it most, a vaccination rollout probably can’t be launched successfully until after January 20 (assuming Biden and Harris win the election).

          1. confused says:

            Eh… if Biden and Harris win the election, I think that will change perceptions a lot, especially if they come out in favor of the vaccine (after the election).

            Also, I think there will be a lot of natural immunity by then… Even with an October approval, I doubt most of the population will be vaccinated by Thanksgiving or even Christmas.

            Most of the US states, and I think all the ones with large populations, have had a major “wave” or “surge” of infections by now. So US COVID deaths should drop sharply going forward. After two months or so of that, a lot more people will probably basically give up on precautions…

            And if treatments improve and if that lack of precautions is more among younger people, deaths might not rise again much (the July-August surge peaked at something like 1070 deaths/day 7-day average, while the April peak was well over 2000) so that might not change.

          2. David G Whiteis says:

            You’re very likely right about the deaths, but I don’t forsee a significant drop in new cases, especially if ” a lot more people will probably basically give up on precautions” (which will only happen in states where precautions aren’t mandatory and enforced — and probably won’t happen at all if Biden makes good on his promise for a national mask mandate if he becomes President).

            And yes, shingles is a re-emergence. I wasn’t sure if what you experienced was a re-emergence or an actual re-infection (which, until now, has been the question about a lot of these COVID “re-infections,” as well. I apologize for the confusion.)

          3. David G Whiteis says:

            . . . and with an October approval (which in my opinion would be disastrous, but let that go for now), widespread distribution and uptake wouldn’t come close to happening until well into 2021. Even the most optimistic estimates (e.g., Fauci, Slaoui) have it that if a vaccine is approved in late 2020 or early 2021, the general public won’t have access to it until mid-summer sometime. They’re also saying that something approaching “normality” could return by “late 2021,” but that sounds awfully optimistic to me — we have over 300 million people to vaccinate, at least 25% of whom have no health insurance, many of whom live miles away from any place where they could be vaccinated, at least 35% of whom will probably refuse to get vaccinated at all . . . the logistics are beyond daunting. And you can ramp that up to “daunting-squared” if, as expected, the vaccine requires two initial doses.

          4. confused says:

            What I had was definitely not shingles, its symptoms are quite different from classic chickenpox.

            As for deaths vs. cases… cases will probably remain relatively high, sure, but at this rate naturally-acquired immunity will probably prevent it from being too dramatic by this fall.

            Sure, reinfection is now known to be possible, at least at n=1. But *symptomatic* reinfections are probably exceedingly rare, as we would have more than one confirmed (asymptomatic) case by now if they weren’t, given that tens of millions of people must have been infected in the US alone.

            Even if the President has the power to issue a national mask mandate (public health orders are generally a state-level power) many states would not actually enforce it, so it would not actually keep people from giving up on precautions.

            I cannot see states like TX FL etc. continuing to care much about precautions once deaths drop down to a low level.

            I think vaccine distribution problems are being heavily prepared for, so it might not be that bad time-wise. And we probably don’t need that high of an uptake rate, especially since so many people will already have antibodies!

          5. David G Whiteis says:

            I do think that states should have mask mandates. As much as I loathe the damn things and they depress the hell out of me, I realize they work, and we should all use them.

            My main problem with a national mask mandate is its “one-size-fits-all” nature. Different areas, with different levels of severity, should have some flexibility (e.g., only mandating masks indoors, or possibly, as New Zealand is doing, mandating them in certain potentially high-risk situations, such as mass transit). And at some point, if conditions in a particular state became safe enough for that state to open up more completely and begin allowing larger public gatheirngs (e.g., festivals, book fairs, athletic events, etc.), they shouldn’t be hindered by a national mandate that doesn’t apply to their specific situation.

          6. confused says:

            I think any statements about national mask mandate now are essentially meaningless.

            It’s August. Even if Biden wins in November, he won’t actually be President until late January.

            Unless deaths rise again (and I don’t think they will), I don’t think there will be much public support for national mandates by then. And a President might not want to issue a mandate that is questionably constitutional (this sort of thing is generally a state power) *and* would probably be totally ignored by roughly half the states.

            So even if Biden *now* thinks it would be a good idea (and one can’t really trust candidates’ statements before an election…) that might change as conditions change.

          7. David G Whiteis says:

            Okay, but remember — it’s not just about deaths, but about new cases severe enough to require hospitalization (and/or have serious, long-lasting comorbidities). I’m not seeing any evidence in a noticeable declne in these.

            And as long as new cases of any kind continue to show up, the fear quotient will remain high. Without a widely available and successful vaccine (and maybe –probably — even with one), I don’t see most people, and certainly not most health experts and policy makers, relaxing much, even if severity begins to slowly ratchet down. (I’m not talking about “special cases” like the Sturgis bikers, the young folks having house parties and rave parties, et al. They’ll keep doing their thing regardless of what’s going on around them, and regardless of the consequenes to others.)

  20. An Old Chemist says:

    08-21-2020: (This is after Derek’s Post About this Data)

    Pfizer and BioNTech Release Additional Early-Stage Data on COVID-19 Vaccine
    Published: Aug 21, 2020 By Mark Terry

    1. David G Whiteis says:

      “. . .in the older group, the average level of antibodies against the virus was only 41% of what was observed in the younger group. The study, however, indicates that was still higher than antibody levels observed I patients who recovered from COVID-19.”

      Still somewhat hopeful news, but I admit I’m still eagerly awating the data from the Novavax trials, since their vaccine has been buttressed with the adjuvant which should, in theory, increase the possibility of its effectiveness older and other at-risk people.

  21. An Old Chemist says:

    Hong Kong man, 33, ‘is world’s first official case of contracting Covid-19 twice’

    1. Michael says:

      A helpful explainer from a virologist on the Hong Kong case:

    2. Ol' Bone Spurs says:

      * make sure you don’t get convalescent plasma from this dude 😉

    3. confused says:

      Not sure what this tells us, until we know how *frequent* reinfection is. Diseases that normally give lasting immunity after recovery still aren’t 100% (I had chickenpox twice, which “typically” isn’t supposed to happen).

      I never really expected natural infection (or even a vaccine) to 100% eradicate COVID worldwide, so I’m not sure this really changes the picture. If anything, it might be positive, since apparently this was an asymptomatic infection the second time?

      1. David G Whiteis says:

        In that sense it’s positive, except that now we have another asymptomatic carrier running around who can infect other people. That’s probaly my most gut-wrenching worry about this entire issue. (And by the way, chicken pox DOES come back, rather commonly — it’s called shingles.)

        1. confused says:

          Yes, possibly… although not all asymptomatic people are infectious, or at least very effectively infectious, right? So who knows, maybe those who already have some immunity are less likely to be super-spreaders? With only one documented case of reinfection, I don’t see how this could be known.

          But yeah, it wouldn’t lead to the virus *dying out* due to natural immunity. But I never expected that anyway. It could lead to it being reduced to “just another circulating respiratory virus”, though – like the “common cold” coronaviruses.

          Isn’t shingles a reemergence of virus latent in the body rather than a new infection? IIRC chickenpox does generally prevent re-infection.

          1. David G Whiteis says:

            RE: “. . .not all asymptomatic people are infectious, or at least very effectively infectious. . .”

            Unless I’m misunderstanding you, I’m wondering where your data are from. I believe the CDC estimates that as many as 40 percent of coronavirus transmissions are from asymptomatic carriers — and recent reseach indicates that children, while usually asymptomatic, may actually be far more contagious than adults.

          2. Michael says:

            The other wrinkle with the Hong Kong individual is that he appears to have been the rare case not to have seroconverted after his first infection. He seroconverted after the second infection, but it appears that the immune response which kept him asymptomatic the second time came from another part of immune memory (T-cells?).

            Plenty of commentary that this shows that vaccines that generate more of an antibody response are necessary for herd immunity rather than natural infection, and that’s certainly the safest path to herd immunity, but that point would be more clearly made if he (like most) had any neutralizing antibodies after his first natural infection.

          3. confused says:

            I’m not arguing that asymptomatic and/or presymptomatic spread isn’t important to the spread of the disease overall.

            But I thought it varied a lot how contagious individuals are: some are super-spreaders, whereas I think there was a study where they followed 400+ contacts of one case and none of them had it?

            IE – We can’t know whether reinfections have different contagiousness characteristics (since we only have one confirmed reinfection so can’t do statistics) unless the cause of why super-spreading happens is well enough understood to confirm/rule out reinfections being different from initial infections.

        2. David G Whiteis says:

          Michael, your observation points yet again to the way so much mainstream news commentary misses the subtleties and details of very important issues. I admit I didn’t know that he had not seroconverted after his first infection. Would this make him enough of an outlier that we can’t use his case to say (for sure) whether there is a risk of re-infection for most people? Might it actually be an encouraging sign for the longer-term potentil efficacy of the vaccines being tested by Pfizer and AstraZeneca (if Trump doesn’t bollix that one up with his damn bloviating), among others, which do stimulate memory T-Cells along with antibodies?

          1. confused says:

            Yeah, I don’t know enough about the immunology to know whether that is unsurprising, or whether that makes this an unusual case from which no conclusions relevant to that

            That’s why I said we’d have to know the *prevalence* of reinfections (not just that it’s possible with n=1) to know if it matters to the overall picture.

            If it’s like 1 in 1,000 people susceptible to reinfection it’s basically irrelevant. If it’s like 1 in 4 that’s different.

            I would say that it can’t be that common since we would have seen lots of cases by now… but if basically all reinfections were asymptomatic, people would have no reason to get tested.

          2. confused says:

            Oops. “…from which no conclusions relevant to *the larger population can be drawn.*”

    4. Marko says:

      Immunity passports all get a new stamp today : ” VOID “

      1. DataWatcher says:

        So much for the dream that reinfected people have less serious symptoms:

  22. Walter Sobchak says:

    So, who needs clinical trials?

    China says it began public use of covid-19 vaccine a month ago, bypassing clinical trials | By Eva Dou | August 24, 2020 |

  23. Marko says:

    After letting the horse out of the barn , Stephan Hahn says ” Oopsie ” :

  24. An Old Chemist says:

    FDA’s Hahn Apologizes for Overstating Benefit of COVID-19 Plasma Treatment

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