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Pfizer’s Progress

I wanted to point out an interesting interview given by Pfizer’s CEO Albert Bourla to Time. I have made some pointed remarks about Pfizer over the years, but this is one of the better Q&A pieces like this that I have seen – you’ll see why in some of the answers below.

Bourla is actually quite optimistic about the Pfizer/BioNTech vaccine program (four different mRNA attempts, as fans will recall). He says that they should have enough data “in the September time frame” to submit to the FDA, with approval, he hopes, in October if the data are strong enough. Is that realistic? Well, if the data are strong enough, yes. But as with all these timelines, that’s what can happen if everything works right the first time (and with enough vaccines being tried, one or more of them could indeed come through like this). What we’ll have are short-term efficacy and safety data: real-world data on protection against coronavirus infection and on adverse reactions on dosing. What we won’t have are the data on duration of that protection, nor a read on long-term safety. But we’re not going to know those for *any* of the vaccine candidates – those are the big corners that the world is going to cut, and I agree that it’s the right move.

He goes on to say that

“. . .it was the moment when I saw the data, plus many other data that we haven’t published yet, [that] made me say that until now I was thinking if we have a vaccine. Now I’m discussing when we’re going to have a vaccine. . .We have a lot of indications that make me feel that really it should make it.”

Remember that earlier this month the company published Phase I data on one of the four vaccine candidates; I very much look forward to more information of this kind. This is where I should mention that (at least as I write this) we still don’t have such information about the competing mRNA vaccine from Moderna, and it has now been eight weeks since they press-released their first results. (Update: they just published this afternoon! Blog post on the way). Meanwhile, on Monday morning Pfizer announced that the candidate they published on (BNT162b1) and one of the other three (BNT162b2) have been fast-tracked by the FDA for development. The former is one of the two base-modified RNA candidates, and despite some digging around this evening I have been unable to figure out which is the other one. From the looks of the number code, it might be the other base-modified one? We shall see. At any rate, they apparently have enough convincing data on that one to show the agency as well.

Bourla goes on to say that they will be starting manufacturing soon on a risk basis (something they’ve never done with a vaccine candidate), and that the company plans to be ready with up to 100 million doses by the end of the year – and over a billion doses next year. When the Time reporter asked what they’ll do if the vaccine doesn’t turn out to work in Phase II/Phase III, Bourla responded “We will just have to write it off and call it a day. We will throw it away. It’s only money we’re going to lose.” More in this vein:

. . .if you were calculating return on investment, we would never do these things. We were discussing that back in March, what that means to human lives, to the economy of the world. So it was a must, that we must take those measures. . .The vaccine should be free to all people. We are not giving it away to governments. We are going to charge governments … a very, very nominal value. But our intent is to ask governments that they should, for these prices, they should provide it free of charge to all citizens.

He makes the point, as others have, that this is a chance for the drug industry to show what it can deliver for the world. And he’s right: no one else can do the things that the biopharma industry of the industrialized countries are doing right now. If there’s going to be a cure, it’s going to come from us. No one’s going to combine two things from the grocery store and find the wonder drug – that’s what you get from lazy screenwriters cranking out a cheap movie. “My God, that’s it! Nutmeg and anchovies! Under our noses all along!” Nope. It’s going to be the result of a lot of hard work and a lot of expertise in immunology, molecular biology, formulations, pharmacokinetics, protein science, clinical trial design, statistics, toxicology, manufacturing logistics and a whole lot of other subjects that many people would rather break rocks all day than have to pass an exam on. Oh, and a lot of money, too: Pfizer (just one company in the race) is apparently spending about $2 billion this year on this program, and as many have noted, in their case none of it has come from the US government. The folks who claim that new drugs only cost a few million and that they all come from the NIH anyway are going to have to make an exception this time, looks like.

So good luck to Bourla and to the Pfizer/BioNTech collaboration as they push on in the clinic. Those Phase II/III trials are where all of this is going to be settled, because there is simply no other way to find out what works. Not everything will. We’re heading into an immense, unprecedented, and incredibly expensive and nerve-shredding pile-up in the clinic later this summer and fall, and I’ve said it before – we’ve never seen anything like this, and I hope we never have to again. Hold on tight.

 

 

133 comments on “Pfizer’s Progress”

  1. Stephen Levy says:

    The public health officials (Fauci, Gottlieb) seem to estimate probability of a successful vaccine in the range of 50% or higher. Can anyone describe how to arrive at that order based on number of attempts, probability per attempt, and correlations of approaches? Hard for me to tell as an outsider how to justify between 0.1%, 1%, 10% chances here. Thanks.

    1. Barry says:

      Over the 150yrs of vaccine research, pathogens that produce vigorous “flu-like symptoms” (i.e. that evoke a robust immune response) are good candidates for a vaccine. Pathogens that don’t (e.g. HIV) are not. Covid 19 is not a slam dunk; nothing is. It is novel. We have never faced a viral infection that e.g. blocks the host’s expression of interferon1, and that activates complement/clotting directly. But it’s a good candidate for a vaccine. That “>50%” value is not mathematically derived, but conveys the belief that it is the time-frame that is wholly novel, not the immunology.

      1. Jason says:

        As I was taught in 6th grade, the original vaccine was Edward Jenner’s use of cowpox (cow = vacca) to counter smallpox in the 1790’s, so not 150 years, but over 200.

        1. Ian Malone says:

          And Jenner wasn’t the first to come up with the idea; people had previously known smallpox exposure conveyed immunity, and so had been innoculating with matter from smallpox sufferers for a few hundred years before Jenner’s experiment (apparently documented in China from about 1500AD). However Jenner’s work might be the first application of scientific method to vaccination.

          1. Jeff W says:

            It seems as if Zabdiel Boylston in Boston in 1721, urged on by Cotton Mather (of all people), might have been been the first with a scientific method of sorts. According to one site, “Mather and Boylston had collected surprisingly thorough data that made a clear argument for the effectiveness of inoculation. Boylston, who had personally inoculated some 287 people, recorded that of those inoculated only 2% had died. In comparison, the mortality rate of the naturally occurring disease during that year was 14.8%.”

          2. eub says:

            Cotton Mather reportedly first heard of variolation from a West African man named Onesimus whom he bought as a slave, and informed himself about African and Turkish practices.

            Mather had previously lost his wife and several children to measles, and I wonder if that was part of his motivation against this other disease.

    2. Mark says:

      The “(number of attempts) * (probability per attempt)” metric is the wrong way to think about it. Speaking purely mathematically, the flaw is that the attempts aren’t independent. But regardless this wasn’t arrived at on a spreadsheet.

      As Barry explains, basically people are looking at this virus and seeing it is “like” other viruses that we have vaccines for. So the actual thinking when people spout out “50%” is more like: The base rate of success on similar viruses we’ve made an effort is 80% (to make up a number). Then we’re trying to do that very quickly, so you reduce that, but we’re trying harder and with more resources than ever before so you increase it, and Fauci’s seen more data coming in that removes some risk so you increase it.

      There’s a way to express this approach more mathematically but no one’s done the exercise and it wouldn’t matter much. Basically people are drawing on their professional and scientific expertise to make a judgment about whether this is like the sort of thing they’ve seen work. It’s highly uncertain, but ultimately fifty percent should be considered like a Fermi estimate: They think it’s not 10%, not 90%.

    3. Max says:

      Shorter answer: it’s a complete guess, “multiplied” with “we need to be seen as somewhat optimistic”. No one has a clue. And no, “looking at 150 years of vaccine research” really doesn’t help much, clearly this virus is somewhat different from others and the closest idea we could get would be by looking at viruses from the same family, the coronaviridae. However, there are no vaccines for coronaviridae in humans. Meaning, again, there is no way to make any even educated guesses. It’s “we need to make the public feel less pessimistic”.

      1. confused says:

        I do think there is some reasoned basis for optimism. We know that the immune system does work pretty well against SARS-COV-2 in most cases, i.e. most people who are infected clear the virus and recover. This isn’t something like HIV.

        Sure there are no human coronavirus vaccines — but the four common cold coronaviruses don’t warrant developing one, SARS died out too quickly for vaccine development, and MERS is incredibly rare.

    4. Polynices says:

      Either it works or it doesn’t work. That’s a 50% chance of working!

      1. Thomas says:

        Actually, there is a chance that a vaccine ‘somewhat’ works. Not perfect, but good enough for now.
        Something that would have been seen as a failure in less-hasty times. For example 70% effective. Or effective for half a year only. But that could still be useful now.

      2. Another Guy says:

        If the weatherman (weatherwoman?) says 50% chance of rain, then it means they have no idea if it will rain today. However in drug and vaccine discovery, I would interpret 50% probability of success meaning things are shaping up a lot better than the usual ballpark 10% success rate. 50% could also be interpreted to mean the first vaccines will help keep many patients in the ICU off the ventilator, and hopefully lower the infection rate in front-line workers.

  2. Alan Goldhammer says:

    The lack of comment on the part of Moderna is interesting. A colleague offered me a wager that the Moderna vaccine wouldn’t work out. I didn’t accept as I have the same feeling. We’ll see. It’s surprising that so much effort is focused on mRNA vaccines.

    1. Derek Lowe says:

      It is indeed – the delay in publishing the full Phase I data is doing them more harm every week, as far as I’m concerned, building suspicion that the numbers are perhaps nothing to boast about? What else are people to think? Eventually the choices come down to lazy, disorganized, or trying to hide something. The good or at least neutral reasons gradually fall away.

      1. TallDave says:

        has anyone asked the NIH?

        https://www.fool.com/investing/2020/06/04/heres-why-moderna-only-released-limited-phase-1-da.aspx

        The compromise is usually that some top-line data gets released early, but not nearly enough to satisfy investors. Such was the case for Moderna (NASDAQ:MRNA) when it released data for just eight of the 45 participants in the phase 1 clinical trial testing its SARS-CoV-2 vaccine, mRNA-1273.

        “The NIH is running the study, and they want to be able to publish the data,” CEO Stephane Bancel explained Wednesday at the Jefferies 2020 Healthcare Conference, which was held virtually.

        1. TallDave says:

          I think it’s this one?

          https://clinicaltrials.gov/ct2/show/NCT04283461

          doesn’t seem to be in Modern’s power to publish this data, at least if we believe the article

          1. TallDave says:

            fwiw here is the Phase 2 trial, presumably similar caveats apply
            https://www.clinicaltrials.gov/ct2/show/NCT04405076

            interesting tidbit there is they dropped the 250 dosage and kept only the 500 and 100… suspect that means they are no longer as concerned about efficacy… obviously more dosages would be available at 100/50 than 250 so that might help deployment logistics

          2. TallDave says:

            50 not 500 arghj

          3. Bats says:

            The Phase 3 trial information has just been released! The 100 dosage, twice over a month. Starting July 27.

            https://clinicaltrials.gov/ct2/show/NCT04470427

          4. TallDave says:

            Thanks Bats. Looks like they settled on 100 for Phase 3.

            Experimental: mRNA-1273
            Participants will receive 1 intramuscular (IM) injection of 100 microgram (ug) mRNA-1273 on Day 1 and on Day 29.

            and now https://www.youtube.com/watch?v=uMyCa35_mOg

          5. Dave J Price says:

            sorry Bats, got excited and clicked the link then wrote the same thing you did before actually reading your comment 🙂

          6. TallDave says:

            …. and there we go

            https://www.businesswire.com/news/home/20200714006042/en/Moderna-Announces-Publication-New-England-Journal-Medicine

            Interim analysis of original cohorts of Phase 1 study evaluated two-dose vaccination schedule of mRNA-1273 across three dose levels (25, 100, 250 µg) in 45 healthy adults ages 18-55 years; results reaffirm and expand upon positive interim data announced on May 18th

        1. Steve Scott says:

          Can’t wait to get Derek’s take on this. Particularly the results in Table 2. There seems to be a drop in most of the levels between day 43 and day 57.

          1. Derek Lowe says:

            Coming up first thing tomorrow!

    2. Anon says:

      Just my opinion, but I think there’s a software “information coding” purist bias that makes the mRNA vaccine very attractive to the types of Bill Gates and backers, one where biological systems can be hacked with code etc. Time will tell, one can’t but be impressed by the simplicity of that approach, but as we all know biological systems are infinitely more complex and capable of severe collateral damage. Irrespective of the prospects of mRNA vaccines, there’s a whole six-degrees of separation stock trading universe that has a life of its own outside of what the drug approval prospects of these vaccine candidates are in reality. Always found that amazing about the stock market.

      1. EJ says:

        The biotech overoptimism is the least crazy trend in the stock market now, unfortunately.

  3. Dixon says:

    Are all the Pfizer/BioNTech candidates RBD-only targeting?

    1. gcc says:

      According to the following webpage, two of their four candidates encode full-length spike protein and two target just the RNA-binding domain of the spike:

      https://www.precisionvaccinations.com/vaccines/bnt162-sars-cov-2-vaccine

      Here are the key details from that page:

      —–
      BNT162b1 and BNT162b2 are both nucleoside-modified RNAs, formulated in lipid nanoparticles.

      BNT162b1 encodes an optimized SARS-CoV-2 receptor-binding domain (RBD) antigen, while BNT162b2 encodes an optimized SARS-CoV-2 full-length spike protein antigen.

      In an ongoing Phase 1/2 placebo-controlled, observer-blinded clinical trial, nucleoside-modified messenger RNA vaccine candidate expressing the SARS-CoV-2 receptor-binding domain (RBD) is being evaluated in 45 subjects. This study was last updated on June 29, 2020.

      Two of the 4 vaccine candidates include a nucleoside modified mRNA (modRNA), one includes a uridine containing mRNA (uRNA), and the fourth vaccine candidate utilizes self-amplifying mRNA (saRNA). Each mRNA format is combined with a lipid nanoparticle (LNP) formulation.

      The larger spike sequence is included in two of the vaccine candidates, and the smaller optimized RBD from the spike protein is included in the other 2 vaccine candidates.
      —–

      I’d be curious to find out which antigen (RBD only or full-length spike) is in the self-amplifying mRNA candidate, but haven’t seen that information anywhere.

      I really like that Pfizer/BioNTech are testing multiple candidates in people. I’ll be interested to see how many make it to later stage trials.

      1. Steve Scott says:

        A few months ago, Pfizer said it intended to narrow the number of candidate vaccines down to one or two in the Phase II study. Maybe the announcement that the first two candidates have been fast-tracked, means that #3 and #4 have been dropped (including the self-amplifying version).
        Here is some insight from an April 29 article by Fierce Biotech, quoting Mikael Dolsten, Pfizer’s chief scientific officer:

        “The first one already dosed. And that allows us more than anyone to cherry pick from a new disease like COVID-19, what mRNA [ph] type, what antigen is the most effective and allows us to pick one or two to move into pivotal studies. So, that covers unmodified mRNA, modified and self-amplifying. To the best of my knowledge, we are the only one currently having self-amplified mRNA in the clinic, which would allow you to dose, at lower dose than any other construct.

        “We already have animal data from rodents on the various constructs that are encouraging. And we also have data from patients here that shows that the two antigens that we pick seem to be the most relevant for intervening and utilizing viruses. And by having picked two, spike or the smaller components receptor binding domain again, I think we will be able to cherry pick what turns out to translate most effectively in man.”

      2. Dr. Manhattan says:

        “two of their four candidates encode full-length spike protein and two target just the RNA-binding domain of the spike”.
        I think you mean the Receptor Binding Domain, not the RNA binding domain. The spike doesn’t bind RNA. Easy to get confused as the vaccine is composed of RNA.

        1. gcc says:

          Rats! Yes, I meant receptor-binding domain. I should have just stuck with the acronym… ha ha. But yes, thanks for the correction.

  4. For myself, the key discussion element is “duration of response”. I’m sure we are also going to get a lot of T-cell data from these vaccines, but not just serology, and this will be very informative in terms of protection. (Edited to put in a missing word, per the commenter’s next post, which I’ve now deleted – DBL)

    If any of the vaccine candidates offer efficient short-term protection (say 3-6 months) then this would be an enormous step forward as we head into the 2021 ‘flu season. It won’t be ideal, but it will be a real step forward. Longer-term protection may come with seasonal boosters.

    Besides, people are used to an annual ‘flu vaccine and will probably take an annual COVID one, too, if it comes to that. This has been a spectacular effort and let’s not forget the ethos of providing the vaccine free at the point of care.

    Best to all, and thank you, Derek, for all the work you put into this.
    GOP

  5. mallam says:

    If only. Show Us The Data.

  6. FoodScientist says:

    Derek, what do you think will become of social distancing/masks if the vaccines only end up working for 50% or 70% of people? It would still be not herd immunity levels. Think everything would just re-open and say good luck to the susceptible folks?

    1. Derek Lowe says:

      Now that is the big question. I’ve been thinking about that one, but nothing productive has emerged yet. I’ve decided that I’m just going to wait for more data and see how to play the hands we’re dealt, since there are just too many possibilities to work through otherwise. But your point is very valid indeed.

    2. Michael says:

      I agree with Derek that we have to wait and see. But is it really likely that “working” for people will be a binary proposition — sterilizing/neutralizing immunity for 70%, zero effect on 30%? I would think it would be a continuum of effectiveness, so long as it’s safe in everybody. Reopening might be possible without a blithe “good luck” if it confers partial protection on the “unprotected” cohort.

    3. Michael says:

      50-70% efficacy would be enough for herd immunity even with pessimistic models (1-1/2.4 = 58%) with a decent amount of compliance given that 7% have already been exposed; varying susceptibility and uneven contact network structure likely lowers this 58% to something like 20-35%.

      A better question is, what if efficacy fades to, say, 30% in a 6-9 months. That’s enough to improve individual safety and slow things down, but not enough to make someone vaccinated feel safe or stop spread in the population. In turn, that’s likely to lower the number of people getting boosters.

      High efficacy would be good because we could feel safe even if others don’t get it. Unfortunately, efficacy in the most vulnerable populations is likely to be lowest, and the populations that most need to be vaccinated in order to arrest the spread of COVID-19 are much less vulnerable.

      1. WST says:

        Vaccines’ populations impact should actually work better then what can be predicted from SIR or similar “herd immunity” models.

        The vulnerable group gets vaccinated first and this should protect the population layer that gets infected first, easiest and suffers most. Next group will be health workers, incidence statistics and serological studies (Spain) show that they have significantly higher risk of infection.
        “Herd immunity” efficiency depends on how well Susceptible and Resistant are mixed, it’s this randomisation that is a promise of the virus extinction, so rest of the population needs to be vaccinated as well, but removing most vulnerable groups shroud already break epidemics dynamics.

    4. x says:

      Considering that we presently have NO vaccine, i.e. 0% effectiveness, and states all moved to reopen while the pandemic was still an imminent threat even though that was clearly wrongheaded and insane, and mass numbers of people aren’t bothering to wear masks or avoid social contact, I can very confidently guess it would be back to pre-COVID normal (with a handful of proactive individuals who continue to wear masks outside work, mostly in liberal urban areas where wearing a mask won’t be taken as an ideological attack) and every man for himself.

      Then again, if we had a vaccine with 70% efficacy, it might do us more good than all these quarantines and lockdowns and things that are largely being circumvented by human stupidity. Passive curve flattening…

      1. Liam says:

        See my other comment , it better freaking reopens and goes back to normal, or I wont even take the vaccine! Nobody I know probably will! The side effects make me more sick then the disease likely will, so if the vaccine does not give me my life back (hugs, cosplay, anime conventions, making friends, minglking, karaoke, you know NORMAL FUN SOCIAL THINGS that make life worth living!), why would I take it!?

        Also, I wont accept it. Nobody will accept it. Everyone from the entire Dutch population to the parliament to the PM to the king is just barely excepting (and the exceptions are mounting, and no-one is policing it anymore and in reality no-one is already doing it anymore) an atleast theoretical 1,5metre-society untill the vaccine or treatmetn arrives, but that last point has become a mantra. Its even written into law. The law formalizing the rules that the parliament has to agree to extending every 6 months – if they even pass it which is highly doubtfull.

        Vaccine = back to normal . That is public policy, and not a single expert in my country has said anything else so far. Or government official. Not one.

  7. Kevin says:

    “It’s only money we’re going to lose.”

    Has anyone thought about the environmental implications of at-risk vaccine production. The raw materials do not come from thin air…. 100 million doses of vaccine require vast energy inputs when thinking off all the basic science that goes into developing a vaccine. I am very worried that this is not on anyone’s radar.

    1. NHR_GUY says:

      Kevin/Karen we are literally fighting for our lives and way of life here and you pop up with “muh envirement”. I’m a big proponent of environmental concerns, both professionally and personally. This however is an urgent situation, some things will need to take a back seat for the greater good. You have to look at the bigger picture. Go put your mask on!

      1. Kevin says:

        LOL nice one Jake.

        “You have to look at the bigger picture.”

        How many vaccines will it take to save the human race from impending doom from environmental disaster in 100-200 years or less?

        1. confused says:

          It’s probably not so much a threat of “impending doom” to “the human race”.

          Pollution and climate change are real and critical problems with huge implications for human health/well-being – but talking about total collapse of civilization, extinction of humanity, or other stuff well beyond the evidence IMO harms the message overall. The things that are clearly probable from the evidence we have* are bad enough already to warrant major action.

          *greatly increased refugee crises, general increase in poverty/hunger in areas already on the “edge of subsistence”, wider exposure to vector-borne diseases, general impoverishment of biodiversity & loss of biological resources, etc etc.

          And the buildout of vaccine manufacturing just can’t have that much of a carbon footprint compared to, say, all the commuting not happening. 2020’s carbon footprint will almost certainly be less than 2019.

          1. Kevin says:

            Did you know the pharmaceutical industry has a ~50% larger carbon footprint than the automotive industry?
            Link: https://www.sciencedirect.com/science/article/abs/pii/S0959652618336084

          2. Chris Phoenix says:

            Kevin misread the article (the blog won’t let me reply to him). That article is talking about emission intensity – that is, emission per money spent, not net emissions. On the other hand, the pharmaceutical industry is very approximately twice as big as the automotive industry, so releases 3X as much carbon not 1.5X. On the gripping hand, the “automotive industry” is only about building cars – which then go on to burn (very approximately) their weight in fuel each year. So pharma produces a small fraction of what cars produce.

            And even though the covid vaccine effort is using a huge amount of resource, it’s a tiny fraction of the overall pharma industry. So the additional emissions are detectable, but very small compared to not-driving.

        2. Kaleberg says:

          It doesn’t stop meteor strikes either.

      2. FoodScientist says:

        Bruh, muh environment…..

        To be honest producing 100million doses of birth control or basic sanitation is probably going to save more lives or do more for the environment/ human quality of life than an equal amount of 100million doses of the vaccine that may or may not be needed. It’s kind of like in the 1960s when we had the option of going to the moon or ending world hunger.

        1. confused says:

          “It’s kind of like in the 1960s when we had the option of going to the moon or ending world hunger.”

          If by “we” you mean the US, we never had that option. World hunger is fundamentally a problem of infrastructure. (Enough food is already produced to feed everyone.)

          The US in the 1960s was involved in a bunch of proxy wars in poorer/less developed nations as part of the Cold War. Any attempt to massively build out infrastructure in poorer/less developed nations at that time would have been seen as just part of Cold War jockeying for global power, and thus would not have been very well received by many of those nations.

          And it would genuinely have *become* jockeying for global power, in that time, however good the motives of the project’s original initiators were.

          Even today, outside the Cold War context, we’d essentially be asking a lot of other nations to be indefinitely dependent on us for life-supporting infrastructure…

        2. metaphysician says:

          What makes you think for a second that was the choice available? Perhaps we had the choice, in the 60s, of either going to the moon or *trying* to end world hunger. I am more than confident that the effort would have ended in abject failure. One is an engineering challenge that could be solved by good engineering practice. The other is a social systems problem that essentially requires solving easy little problems like “How do you fix a corrupt government?”, “How do you organize the entire world when most of the world does not agree on even basic foundational principles?”, and “How do you stop the 1-5% of people who are complete sociopathic monsters from screwing over everyone else within reach?”

    2. confused says:

      It’s a tiny portion of the overall environmental footprint of industrial civilization as a whole.

      Any negative impact is going to be much smaller than the positive impact of reduced pollution from more teleworking rather than commuting this year. (Cars are the single largest source of air pollution in most US large cities.)

      It will be very interesting to see how the “smog” numbers for the 2020 ozone season turn out, this fall/winter.

      1. Fraud Guy says:

        Overall, IIRC, the largest contributor to US carbon footprint is our farm animal population.

        1. Helium says:

          Farm animals emit about 4% of direct US greenhouse gas emissions. Transportation is the largest emitter at 28%. See https://www.epa.gov/ghgemissions/sources-greenhouse-gas-emissions

          If the full life cycle is considered, the farm animal contribution might be as much as 8%, but it’s hard to say. Apparently no one has done a life cycle greenhouse gas analysis for all US economic sectors.

          1. confused says:

            That sounds more like it.

            Also, a lot of that farm animal population is likely replacing native wildlife in the same areas. There are more cows in the US than there were bison 200 years ago, but it’s a factor of 2 or thereabouts (~100 million cattle vs. maybe 50 million bison) – not like a factor of 10 or something.

            Pigs probably contribute a lot of methane, but still…

          2. loupgarous says:

            Or done an analysis of replacement what would happen if current agriculture of meat involving evolution of CH4 from enteric fermentation were replaced by culture of food animal tissue which doesn’t entail enteric fermentation. We’d get that as a bonus from improved food security if we stopped eating animals which fart, while we fatten them up in feedlots, and just cultured their muscle tissue.

            How to do that isn’t immediately obvious, but the accompanying reduction in CH4 emissions (remember, CH4 is 28-32 times as effective a greenhouse gas as CO2) and effectively eliminating zoonotic spread of influenza and coronaviruses from birds and bats through feedlot animals such as pigs, cattle, etc would seem to be worth the trouble.

    3. sort_of_knowledgeable says:

      The environmental implications of at-risk vaccine production of 100 million doses has to be compared to the environmental implications of treating of million people hospitalized for treatment.

    4. HelenS says:

      I suspect it would be balanced by the good effects of the lockdown on the environment.

    5. sPH says:

      How many bottles of beer are consumed globally and sent to the recycling plant every month? One billion? How much glass is in a beer bottle compared to a vaccine bottle? Send the unneeed vials to a solar-powered glass furnace and move on.

      1. PV=nRT says:

        Justice Kavannaugh in the house.

  8. ezra abrams says:

    I don’t understand how we get safety data that is real in less then several years
    Am I missing something ?

    Can you imagine the public relations catastrophe if the vaccines have some side effect ?

    and what are our backup plans if the vaccines aren’t ready , except for hi risk, by late 2021 or 2022 ?

    Am I wrong to be terrified that a rush scenario, with enormous global pressure, is letting us say safety is ok if we do X people for one year vs the normal X/n for five years, n ~ 5 ?

    we are already

    1. Michael says:

      There’s potential long-term risks, but it would be a very big surprise if they’re big compared to the risk we’re all incurring from COVID-19 today.

    2. Barry says:

      The duration of Phase One is always somewhat arbitrary. The glaring case is bisphosphonates. Because they never clear from the body, logically Phase One should have been life-long. But the FDA recognized that osteoporosis was an unmet need, and settled on 3yrs. Unsurprisingly, there are long-term consequences

      https://www.fda.gov/media/94176/download

    3. Max says:

      No you’re not “missing anything”. And no, it wouldn’t be a big surprise if the long term risks were pretty nasty. There have been plenty of vaccine disasters, even with “normal” development procedures. Look up Dengvaxia, as one recent example. Also, I wouldn’t see it as a “public relations disaster”, but a potentially severely politically destabilizing event.

      The reasoning behind these vaccines seems to be effectively, “it’s unrealistic for the US to engage in effective measures of social distancing, thus a vaccines is our only hope.” The risk though is obvious: you already have riots due to people not being able to reconcile “muh rights” with wearing masks. Now, entertain yourself with the idea that “hundreds of millions” of people in America get such a vaccine, maybe in autumn, then in spring next year, Facebook goes ballistic with people developing Guillain Barré syndrome? Maybe the makers behind “Contagion” should have done the sequel where they show what really happens – most likely, not a miracle vaccine.

      1. TallDave says:

        eh we release new flu vaccines every flu season

        biggest vaccine risk seems to be infection, which is why mRNA is intriguing — there’s no nuclear penetration, it just tells your cells to make the spike and then your immune system says “wtf is with all these spikes, we better figure this out asap” but since the spikes aren’t attached to a virus they don’t actually hurt you

        and then of course when actual spiky virus comes along your body says “hey! spikes! I remember those!”

        I apologize for the above summary

      2. confused says:

        I doubt it will work like that. Sure a high rate of serious vaccine side-effects might stoke anti-vaccine sentiment in the US somewhat. But there is no way that vaccine side effects would be anywhere near as socially-destabilizing as the current social distancing measures are, even if it was 100 times worse than the 1970s swine flu vaccine.

        Current social distancing measures are putting a lot of stress on society because they affect everyone, and the disease doesn’t (so far)*. Vaccine side-effects are just not going to have that level of visibility/broad effect, even with Facebook.

        *A lot of people in many parts of the US still don’t know anyone who has had COVID. (I don’t… unless you count hearing second-hand that someone I apparently met 5 years ago, but don’t actually remember, had it.)

      3. x says:

        “muh Guillain-Barre” seems to be the new antivax talking point.

  9. David says:

    “My God, that’s it! Nutmeg and anchovies! Under our noses all along!”

    If those had been under our noses, we would have noticed.

    1. Lappan says:

      Spreading such rumors is a vile thing to do: lockdowns have been hard enough but if there’s a run on anchovies then I’ll have to endure it without the best kind of pizza.

      Anyway without zinc there’s no way it can work.

  10. TallDave says:

    regn-cov2 and LY-CoV555 still seem more interesting at this point

    yes, we’ll need vaccines eventually but being able to cure everyone in the meantime would be nice

    not sure why speculation on Moderna has descended into conspiracy theories but they are vaccinating 30K people this month so we’ll know soon enough whether it actually works
    https://www.cnbc.com/2020/07/14/moderna-will-begin-late-stage-coronavirus-vaccine-trial-on-july-27.html

    1. Michael says:

      If you don’t share your data when others do, people will reasonably wonder if there’s some reason you want to keep your cards close to your vest.

      1. TallDave says:

        see above

  11. Max says:

    @ Ezra

    As Dr Lowe states, “What we’ll have are short-term efficacy and safety data […] What we won’t have are the data on duration of that protection, nor a read on long-term safety […] those are the big corners that the world is going to cut, and I agree that it’s the right move.”

    I have huge respect for Dr Lowe and his effort in maintaining this blog but I’m slightly baffled by this attitude (which seems the prevailing one in political circles and the general public).

    Is it really so clear that cutting this corner is the right move for the world? A vaccine likely won’t have 100% efficacy, meaning its effect wouldn’t be a sudden, complete stop to the pandemic and return to the “status pro ante”. It might in the best case reduce the health burden (by a little, considering the low mortality) and time it takes to end the pandemic. However, the risk of safety issues is real, and given the amount of people that would likely get such a vaccine in an unprecedentedly short amount of time, any safety issue would instantly have enormous consequences. Is it really so clear cut that a badly tested vaccine would be preferable over continuing to optimize clinical management of the disease, combined with persistent and resolute measures of hygiene such that the pandemic eventually dies down in the “natural” way? With optimal social distancing etc, the risk to the average individual is really low from the pandemic, the rate of SAEs doesn’t have to be very high for the trade off to not be favorable any more.

    Personally I pray to the Gods of clinical trialing that these vaccines end in indisputable failures, I would fight tooth and nail if some politician tried to make such a vaccine mandatory (for background, I’m early 30s, PhD with practical experience in clinical trials and pharmacovigilance).

    1. Carl says:

      Any vaccine that does not offer enough short term immunity to produce a sudden and complete stop to the pandemic likely won’t be considered for use until and unless all other vaccine candidates come up short.

      1. Max says:

        Are you really so sure? We’ve seen this with remdesivir – people are all too happy to “grasp the straw”.

        1. Carl says:

          Short version. There’s a bunch of vaccines in development. The grasping at straws with respect to treatments is because we have nothing that works and limited expectation of anything coming along anytime soon. With this many vaccines in development the odds of there not being a good vaccine within a short period of time are very low. You might see low efficiency vaccines rolled out to key workers if the timeframe takes towards the upper end, but mass deployment isn’t likely to be too quickly gone for because there is the high likelihood of a solid candidate appearing a little later.

    2. JaseFace says:

      You are inordinately pessimistic about the risks of vaccination and inordinately optimistic about the prospects both for significantly improved clinical management and for social distancing measures continuing indefinitely, let alone in an “optimal” fashion. The latter is simply not feasible. The FDA has already stated that it will approve anything demonstrated to be over 50% effective. The vaccines are coming, and at least one is likely before the end of the year. And hundreds of millions of people in the US alone be getting them. Best to accept that fact.

      1. Max says:

        See Carl?

      2. Max says:

        It’s probably best not to go too deep into this topic but in many countries apart from the US, it was totally feasible to do social distancing such that daily new cases and daily deaths are at very low levels, with the realistic hope that this can be maintained until the pandemic is over. I concede that my original comment was, admittedly strongly, influenced by the fact that I’m from Europe.

        1. Harald says:

          Max, when and how would the pandemic be over without a vaccine? Getting the virus to die out seems to be an unachievable task. Even South Korea does not manage to achieve this goal, even though they are an island for all practical purposes. Europe is far from that goal (~2500 new confirmed infections in Germany last week alone), let alone the rest of the world.
          So we might be left with social distancing for decades? I’m not sure what harm this would do to both economy and society, but I believe the consequences would be desasterous.

          1. confused says:

            Society would just accept a somewhat higher risk of death (go back to normal without a vaccine) long before “decades”. Remember that far deadlier infectious diseases were once common in the US (yellow fever, smallpox, etc.)

            I am pretty skeptical of support for all but the most basic measures (closing big concerts and sporting events for example) lasting for more than a few months from now.

            In the US right now, some states (TX, AZ, etc.) are seeing rising deaths. But this will probably plateau in the near future. Once things stop rising (even if they plateau at an unfortunately high level) I don’t think it will take that long for the fear to die down.

            The central & interior-west US is pretty skeptical of authority & highly individualist after all… and tends to lean more towards individual responsibility vs. mass social action. And risk tolerance may be somewhat higher in this culture than in the Northeast or Europe – though the difference is probably less dramatic (with growth of cities in TX AZ etc. post air-conditioning) than it once was.

          2. Harald says:

            confused, I agree. But how would this scenario be any better than even a badly tested vaccine?

          3. confused says:

            It wouldn’t! I am absolutely in favor of getting a vaccine as soon as is reasonably possible, and think this justifies expediting things more than (eg) the FDA is willing to accept.

            I was on here a couple weeks ago commenting in favor of human challenge trials, remember…

            China is supposed to be already giving an experimental vaccine to military personnel & businesspeople traveling outside China. I don’t think that government is a gold standard in bioethics (by a long shot), but still…

          4. eub says:

            The science certainly isn’t definitive, but it seems plausible that simply wearing paper surgical masks indoors would hold R < 1. Which is the effective endgame — we're never going to eradicate this virus now, but holding it at a minimal level would be great.

          5. KT says:

            The West and South have a healthy skepticism of authority. Midwesterners are pretty much the exact opposite.

        2. David K says:

          Max, how do you envision the pandemic “ending”? Short of New Zealand-style eradication, which seems unlikely even in Europe–at least without much much more widespread rapid testing–I don’t understand what you mean when you posit an end to the pandemic “in the ‘natural’ way.” Without a high infection rate and natural herd immunity (which I assume we are on common ground in wanting to avoid) or a vaccine, how do you imagine the pandemic ending?

      3. Max says:

        I want to make it clear that I understand and concede your point. From the news that we see here in Europe about the US, yes optimal social distancing etc is sadly not achievable for you. However it makes me even more afraid for the political stability of the US (and the wider world) when I think about what happens when you really pump “hundreds of millions” of doses of covid vaccine into people, and there does turn out to be a safety issue.

        1. Harald says:

          Max, I don’t think there is any reason for „us Europeans“ to be as condescending to our US friends as some of your posts are. Have you seen the footage from Mallorca last weekend? Have you followed the discussion of ending the „mask dictate“ in the past two weeks in Germany? (I’ll never understand the logic of the latter – „it works, so let’s do away with it“). Yes, Europe largely seems to have curbed the pandemic for now. But there is no guarantee whatsoever that we can keep it that way, nor that common sense will prevail.

          1. Max says:

            I considered replying to this but decided not to.

    3. confused says:

      A vaccine doesn’t have to be all that good to allow the world to go back to normal. Just being good enough to reduce COVID to the severity of a “normal” upper respiratory infection would be enough.

      If 50% of people vaccinated are genuinely immune and the other 50% have their risk of death if infected sharply reduced (comparable to some years’ flu vaccine, I think), that would probably be enough.

      1. Max says:

        And here we go. In this scenario, the obvious problem is what is called the “Airbag Effect” in game theory. If you have such a vaccine, realistically you might end up with the problem getting the worse because the effect of people even less practicing social distancing might outweigh the partial effectiveness of the vaccine. And you’re still stuck with the risks of a ridiculously badly tested vaccine.

        1. confused says:

          I don’t think that’s going to be much of an issue.

          People just will not social distance at an useful level into 2021. We are going back to mostly-normal with or without a vaccine by then, society will only support so much.

          A critical factor here is that the risk *to the majority of the individuals in the population* is not all that high. The US median age is ~38 after all, much lower in most Latin American nations, India, etc.

          So in the next (say) 2-3 years the majority of people will be exposed unless a really good vaccine cuts circulation of the virus dramatically.

          Overconfidence about protection due to a somewhat-helpful-but-not-that-great vaccine would speed this up but not really change the overall picture. (In the Americas, anyway. New Zealand and Australia might be a quite different picture.)

      2. Michael says:

        I agree with Confused — that’s an entirely acceptable outcome for a vaccine. Couple that “half immune, half partially protected” vaccine outcome with an effective monoclonal antibody therapy and there is no reason people can’t interact normally with friends, relatives and colleagues. The vaccine can be boosted/supplemented as necessary with refinements.

    4. confused says:

      I had a long comment here that seems not to have posted properly. Basically, that might be true if social distancing was indefinitely maintainable and zero-cost or very low cost*, but neither of those is remotely close to the case. People will slowly go back to normal with or without a vaccine. Human beings are essentially social beings.

      *I mean “opportunity cost” not just financial cost… lost quality of life, lost limited time with elderly family members, mental health impacts of isolation, etc. etc.

    5. Oudeis says:

      I think it’s just the numbers. Look at the cautionary tale of the inadequately tested 1976 Swine flu vaccine, which was condemned because it was given to 40 million Americans and caused 500 cases of Guillain-Barre Syndrome and 25 deaths.

      For comparison, on the optimistic end of the estimates, COVID-19 kills about 0.5% of the people it infects and inflicts lasting damage on at least a few percent more. If half of America eventually catches it, you’re looking at 1.5 million deaths and 8 million people suffering lasting harm. I don’t know anything about these subjects, but it seems incredibly unlikely to me that a vaccine that looks safe through six months of trials could possibly inflict harm remotely on that scale.

      1. confused says:

        Yeah… the 70s swine flu vaccine absolute (per million people) risk of harm was not really that large, it was condemned because that swine flu did not spread, so the harm from the vaccine turned out to be greater than that from the disease itself (one death total).

        COVID has already spread worldwide and proved to be deadlier than, say, seasonal flu or the 2009 pandemic. The same issues just don’t apply for COVID.

  12. David E. Young, MD says:

    There is all sorts of talk of vaccines and the hope that they work. I am hopeful. And there are those who say they won’t work or won’t be enough. Is there any scientific reason to not consider getting two vaccines (or even three)? Understandably this concept would be wickedly difficult to test. But is the idea of two vaccines totally unacceptable? Or should we be thinking along the lines of “this vaccine prevent 65 percent of covid and this vaccine prevents 70 percent, may the two together would prevent 90 percent. Is that at all rational? What do you medicinal chemists think?

    1. Dan says:

      Not a med chemist myself, so I might be wrong on these, but my understanding is that:
      1) If the reasons they’re not 100% effective depend on the person, it’s fairly likely that someone in the “only partly works/doesn’t work” group for Vaccine A is also in that group for Vaccine B if they’re working by similar means. (Put another way, their success isn’t guaranteed to be – or necessarily even likely to be – independent.)
      2) It’s possible that both are safe on their own but interact badly. (I don’t know of a specific reason that would be the case here, but I don’t know of a reason to definitively rule it out either.)
      That’s not to say it couldn’t work, but it’s not as easy as “A mostly works, B mostly works, therefore A+B should work even better”.

      1. David E. Young, MD says:

        All good questions. But…. is it worth testing? The only way to find out is to do the study. Maybe a moot point because the study would require 30,000 participants (10,000 for vaccine A, 10,000 for vaccine B and 10,000 for the combine A and B) and such studies cost and enormous amount of money. But what if vaccines A and B show effectiveness, but not remarkable effectiveness. What if they all are like that. Is it then worthwhile to do the study?

  13. Calvin says:

    https://pharmaintelligence.informa.com/resources/product-content/pfizer-ceo-bourla-wants-profit-from-covid-19-vaccine

    Clearly somebody from Pfizer PR has realized that Bourla needed to walk back the “we’re gonna make a profit from these vaccines” and asked him to spout the “it’s only money” angle.

    I’m going to bet that the reason they haven’t taken government money is because they absolutely want to maximize their profits. If they can not have any pesky government step-in rights that would help. If ever there was a company driven by profit in the face of a global pandemic, it’s Pfizer. It’s always Pfizer.

    So Derek, I take this article with a huge grain of salt. If Pfizer have the best vaccine or even a decent vaccine I doubt they will be able to restrain their natural hunger for profit.

    1. sgcox says:

      “When a fellow says, ‘It ain’t the money but the principle of the thing,’ it’s the money.”

      Kin Hubbard

    2. Mrko says:

      Wasn’t it the Pfizer CEO who said that they refused funding under Operation Warp Speed because he thought it would slow their progress ?

      Seems like a reasonable decision to me.

      1. Calvin says:

        That always sniffed of BS to me. You don’t refuse funding unless you went for it in the first place. Nobody else has complained that it has slowed it down. So it was either they couldn’t agree terms or they weren’t going to get funded and so wanted to save face before they were rejected.

    3. Ken says:

      I don’t recall if it was on this blog or not, but back around April someone commented that, were they a large institutional fund director, they would call every pharma company and say “Your profit on this vaccine is not as important as making it possible for every other company to operate normally again.” I doubt that’s happened but perhaps some companies worked it out on their own?

  14. Mammalian scale-up person says:

    Note on at-scale mRNA type things at risk: it’s not much of a risk, all things considered.

    mRNA synthesized from template processes are limited by how much polymerase you can get your hands on. There’s count em ONE supplier of cGMP polymerase I know of. They’re busy and it’s at a premium. However, Pfizer still has a few old farts like me hanging around who had to brew our own polymerase back in the Olden Days – if it’s for reagent, you can cook it up with synthetic tags, and while it’s an additional parallel operation, it’s not horribly painful and can be done quickly in E coli.

    A commercial scale footprint for mRNA production is about 2000 – 3000 square feet of manufacturing space, another 2000-3000 sq ft of warehouse and storage, much of it freezer storage. Equipment is simple mixing vessels, TFFs, chromatography columns – all smallish scale, what most biotechs consider “pilot scale”. The tricky part is the lipid, but I daresay *someone* at Pfizer has liposome manufacturing equipment laying around. That Andover site has a whole warehouse full of Mystery Equipment, and Pearl River has all kinds of odds and ends that may be pressed into service. Utility demands aren’t a lot, perhaps 200,000L of water for injection per month. Direct costs probably run about $20,000,000 – that’s maybe a liiiiiiiittle more than the Pfizer company Christmas party, but not much more. After indirect costs and ramp up you’re looking at about $40mio. Compared to the cost of the clinical trials themselves, the manufacturing space they’re planning might as well be a rounding error. The project controller likely already has that much in the contingency bucket.

    Mammalian manufacturing that we’d need to do for the Sanofi-GSK recombinant spike, in comparison, would require about 20X the footprint and use a WFI peak of 2,000,000L/72 hours even if running partial single use. Nobody is fronting a billion dollars at risk. Billion, with a B. Not unless we can definitely repurpose it almost immediately.

    1. mymagoogle says:

      I agree on the bulk mRNA, smaller cheaper and faster than one would think – a fraction of every other vaccine production method. A pilot plant size really.

      The fill+finish gets a bit more complicated with materials staging and time demands. There is only so fast a sterile filling line can fill, even if one uses every fill line possible. (…even if 10-dose multidose vials are used (with some kind of preservative))

      I might guesstimate the materials cost closer to $50-75m ballpark all in including F+F, but that is still a rounding error for Pfe.

      1. Mammalian scale-up person says:

        They had a fill-finish suite back in 2005 when I was there, and it was decent size – not the biggest I’ve ever seen, but a good fully-automated contraption. Guessing it filled in the 30,000 items / hour range? Don’t recall exact brand but a comparable size would be Bausch + Stroebel FVF series. Problem Derek has mentioned before – where to get packaging materials, would be the bottleneck, not fill-finish I think.

    2. James Millar says:

      That’s an incredibly valuable perspective that someone like me wouldn’t be able to find anywhere but here. The amazing thing about Derek’s blog is, in addition to the posts themselves, the tremendous quality of comments it attracts (ok, and then there’s all the zinc, but still a lot of wheat in that chaff).

  15. Marko says:

    A good review about COVID-19 immunity drawing on our knowledge about other human coronavirus infections :

    https://www.cell.com/action/showPdf?pii=S1074-7613%2820%2930312-5

    The last line of the paper leads me to think that a lot of what we learn about the safety of a vaccine will come AFTER said vaccine is widely distributed :

    ” Finally, it will be essential, as vaccines are introduced into widespread use, to not only assess efficacy against severe disease and ability to minimize transmission, but also to identify vaccine-enhanced disease, so that vaccination is safe and widely accepted by the public. “

  16. DTX says:

    One key thing about Pfizer’s “optimistic” announcement is that they could have “potentially more than 1.2 billion doses by the end of 2021” is that length of protection provided by the vaccine really matters. That is, 1.2 billion is well-below that needed to protect the world’s population. If the vaccine provides protection for only 3 months, 6 months, 1 year…. it’s even worse.

    Merck’s CEO says the vaccine hype presents a grave disservice to the public. https://www.fiercepharma.com/vaccines/merck-ceo-frazier-says-covid-19-vaccine-hype-a-grave-disservice-to-public

    My sense is that the American public has already given up on social distancing. Unfortunately, it seems like we’ll have to experience much death before it wakes up.

    1. Liam says:

      Well, I certainly dont want to social distance for the rest of my life! I am 28, I have my life before me still, and for the last more then 10 years I have lived for anime conventions, cosplay, free hugs, taking photos together etc!

      Social distancing is literal TORTURE for an extrovert like me. If I had thought those things would never come back again (conventions, hugs, mingling with people, you know normal human being social things!) I would have KILLED MYSELF months ago, and most of my friends say so too, and we all mean it! I am just not going to spend the rest of my life 1,5 metres away from anyone else. Not happening. Period. I dont care if this virus stays endemic or not – it’s no way to life. It’s torture. I want my freedom, hugs, my hobbies, everything what makes life worth living for back!

      Now I can deal without that for 1-1,5 years more untill there is a vaccine or a treatment. But the second that’s here at least in the rich countries (and he can bla bla all he want, but us in Europe and you in USA WILL get it first, and I am quite happy with that), I want to get rid of social distancing rules and life normal again freely mingling with people allowed to hug, have sex, make friends etc like PEOPLE, not robots!

      the primary motivation of the 60-85% of the population here in Netherlands who was wiling to take the vaccine as soon as it is available (and we have already ordered 300 million doses of the Oxford vaccine together with Italy, France, and Germany, so that could be soon indeed) was also “to live in a free normal society without restrictions or fear of covid-19 again”.

      Meanwhile, dozens or hundreds of illegal parties are being held here in the Netherlands alone every week, so many that they’re thinking about reopning dance, night-, and sexclubs again from 1/9 because at least those are safe and they literally cant stop the illegal ones (where they cant tracks who comes for tracing, and also the drug problems etc are much bigger off course. Theyre totally unsafe – people probably even get raped there and what not – but people especially young people are so desperate to socialize and be amongst other people again that thousands go every week).

      Look, again: I can deal with this untill there is some sort of vaccine or treatment. But as soon as there is, I demand to be allowed to have events again and cosplay and mingle and hug and just be a normal social being or I swear I will literally start rioting. Luckily, its also been explicitly proven by the government and experts here thats the plan and is also written into law. A law BTw, which already removed all enforcement of any of the corona rules in peoples houses (making corona parties and poker tournaments and such at home explicitly legal) as parliament simply said it would not pass it otherwise. Thats how fed people are already starting to be with restrictions on freedom.

      And this is Europe.

      I want my life back, so the sooner that vaccine or drug – ANY vaccine or drug – comes, the happier I am, I will take whatever magical miracle juice they come up with, so I can do this again: https://www.youtube.com/watch?v=xoOsATngkJk

      BRING IT!

      1. metaphysician says:

        So, I really feel the need to ask:

        How many *other* people are you willing to kill, in order to get *your* life back?

        1. Liam says:

          Did you read my comment? I said *after a vaccine or treatment arrives*.

          For now, I understand it’s neccesary, but I am NOT going to accept, EVER, that I will never have the ability to go to an anime convention, a concert etc. or hug someone, or have sex with a consenting adult, or take a photo together with someone ever again! It’s lunacy!

          For now, it’s understandable, but you have to agree with me that we can’t just keep social distancing forever right!?

          When the vaccine or treatment is here (I am hopefull we will get both), then, as is written (in law) public policy in the Netherlands (and everywhere), we should go back to normal.

          Me and my friends and everyone should be allowed to do the things we take for granted and that make life worth living again: conventions, concerts, a party, festivals, mingling, making friends, hugging!

          I am NOT going to life the rest of my life staying 1,5metres away from everyone else like a goddamn robot! I’d rather kill myself!

          After a vaccine or treatment arrives, I want my events back! my life! And I can *guarantee* you that that *will* happen, because not only is it official government policy, its also what every single expert here in NL and the entire population keeps repeating like a mantra. And this is a DEMOCRACY – do you really believe that once there are vaccines and treatments, people (and remember, politicians and MPs are people too, PM Rutte keeps saying how terrible he finds the 1,5metre rule himself and how much he just wants to be able to hug people again all the time!)

          We dont expect it to fully go away, ever, just like the flu is here ever year, but once we can control it better with vaccines and treatment, we do plan to , and should, go back to normal (as we also do with the flu!), so that life is free, fun, social, and worth living again! And yes, sadly, some people will die of it every year, just like the flu, but once its not a raging pandemic anymore (at least not here) but brought mostly under control with vaccines and/or treatments, yes, then we should life normally again as the social beings we are, instead of being terrified and depressed and lonely for the rest of our lives never having physical interactions again with our fellow humans or say, an anime convention to meet fellow fans and make new friends! That would be insane! I hope and assume we can agree on that right?!

          We are social beings, and I NEED to socialize, hug people, make friends! Be a person!

          Again, I can deal with it for now, I am talking AFTER we have (mostly) brought it under control with vaccines or treatments, and its just another endemic winter virus like the cold or flu (but likely with a better vaccine, yearly boosters or not, since slower mutation rate, then the flu), one or two years from now! Surely we have to agree on that right?

          People have literally been doing large social gatherings and being social since ancient Egypt and probably before, and it will not and should not suddenly be over after 2020! that is not a world I want to live in, or literally ANYONE I know!!

        2. confused says:

          The same applies for everyone else, though (except for those at super-high risk and really extreme introverts – I’m fairly strongly introverted and distancing is hard even for me).

          It’s just not that clear that losing 50% of your quality of life for 1-2 years to avoid a 1% risk of death is a sensible trade off. And that remains true when you apply it to society as a whole rather than an individual – the “total quality of life lost” is not clearly lower by social distancing.

          I am being very cautious, because I am somewhat of a germophobe and am much more afraid of COVID than is actually warranted given my age and general health status, and because because *right now* my quality of life is not reduced much by distancing. 6 months from now, though?

          If I were at risk of losing my job, for example… to me a 0.1% chance of death (a pretty high estimate for my age, but maybe reasonable given that I’m male and somewhat overweight) is clearly less bad than losing my job. (IE, the “expected loss of quality of life” due to losing my job would be more than 0.1%).

          1. metaphysician says:

            And once again, all these arguments are framed in terms of the risk, to you, and the benefits, to you.

            So, I ask again: if no vaccine proves possible, how many *other people* are you willing to kill, in order to get back your own quality of life?

          2. confused says:

            This doesn’t seem like a sensible framing because *the same risk/benefit equation applies to all the other people too*.

            You’re phrasing it as individual benefit vs. harm to society. But the question should be benefit to society (sum of everyone’s quality of life) vs. harm to society (sum of damage done by the disease).

            [It’s not about what I, personally, do or don’t want to do – I will be *overly* cautious since I’m a germophobe, anyway.]

  17. TabeaK says:

    And here we go with Moderna’s paper (FINALLY): 18-55 cohort only. https://www.nejm.org/doi/full/10.1056/NEJMoa2022483?query=featured_home

    2 doses, good neutralizing Ab response apparently, mild/moderate but transient AEs, especially after 2nd dose.

  18. Louis T Freeh says:

    Which specific tissues, organs take up and express these RNA (and dna) vaccines?

  19. Barry says:

    Moderna points out that you don’t need “specific tissue targeting”, but leave hanging the question of which host cells will be sacrificed to buy immunity

    https://www.nature.com/articles/d41586-019-03072-8

  20. Erik Dienemann says:

    Looking at the Moderna paper, an immunologist I know said the CD4 T cell response is very low (0.15-0.2% make cytokine) and the CD8 T cell response is nearly nonexistent (Figures S10 and S11 in the supplement). They say otherwise in the text of the paper, but the data are the data. I have no idea how to interpret these data, but figured I’d ask.

    https://www.nejm.org/doi/full/10.1056/NEJMoa2022483?query=featured_home

    That also got me to thinking about the Pfizer paper and that one had no T-cell data published that I could see. Seems like a miss to me.

    https://www.medrxiv.org/content/10.1101/2020.06.30.20142570v1

    I also wonder how they would separate out the T-cell response seen in these vaccine trials from any “existing” T-cell response some subjects might have due to cross-reactivity (which has mostly been seen via CD4 and not CD8 cells). The excerpt below is from the recent Nature commentary on this…

    “Pre-existing CD4+ T cell memory could also influence vaccination outcomes, leading to a faster or better immune response, particularly the development of neutralizing antibodies, which generally depend on T cell help. At the same time, pre-existing T cell memory could also act as a confounding factor, especially in relatively small phase I vaccine trials. For example, if subjects with pre-existing reactivity were assorted unevenly in different vaccine dose groups, this might lead to erroneous conclusions. Obviously, this could be avoided by considering pre-existing immunity as a variable to be considered in trial design. Thus, we recommend measuring pre-existing immunity in all COVID-19 vaccine phase I clinical trials. Of note, such experiments would also offer an exciting opportunity to ascertain the potential biological significance of pre-existing SARS-CoV-2-reactive T cells.”

    https://www.nature.com/articles/s41577-020-0389-z

  21. “ No one’s going to combine two things from the grocery store and find the wonder drug“

    So should 2015 Nobel laureate Tu Youyou have just packed up her bags in 1975 and left us without first line anti-malarial therapeutics?

    1. Ben’s Aldehyde says:

      This is massively understating the amount of work and sacrifice made to discover artesiminin and is pretty disrespectful. They don’t hand out Nobel prizes for nothing.

    2. Derek Lowe says:

      That is a bizarre thing to say – I don’t think I made the point I was trying to make to you.

      1. Allow me to articulate the perspective I am coming from:


        I recognize the statement is intended to be about scientific method vs. unsubstantiated practices applied to ‘home remedies’. What I would like to highlight is that everyday plants (whether they wind up in a grocery store or not) when studied with the same rigor as conventional pharma has as much of a chance at resulting in a therapeutic.

        There’s an entire phytochemistry community that’s been academically publishing for decades. Even though people should not be encouraged to think that someone would wake up one day, mix 2-3 things out of their fridge and call it a miracle cure, we should also be encouraging and celebrating the work of the scientists who rigorously study plant-based medicinals.

  22. DrDodd says:

    With multiple companies scaling up production at risk, will availability and not efficacy or safety be the deciding factor on which vaccine you receive if more than one is successful ?

  23. Erik Dienemann says:

    Trying to post this for the 3rd time since last night, lol…can’t figure this site out…

    Looking at the Moderna paper, an immunologist I know said the CD4 T cell response is very low (0.15-0.2% make cytokine) and the CD8 T cell response is nearly nonexistent (Figures S10 and S11 in the supplement). They say otherwise in the text of the paper, but the data are the data. I have no idea how to interpret these data, but figured I’d ask.

    https://www.nejm.org/doi/full/10.1056/NEJMoa2022483?query=featured_home

    That also got me to thinking about the Pfizer paper and that one had no T-cell data published that I could see. Seems like a miss to me.

    https://www.medrxiv.org/content/10.1101/2020.06.30.20142570v1

    I also wonder how they would separate out the T-cell response seen in these vaccine trials from any “existing” T-cell response some subjects might have due to cross-reactivity (which has mostly been seen via CD4 and not CD8 cells). The excerpt below is from the recent Nature commentary on this…

    “Pre-existing CD4+ T cell memory could also influence vaccination outcomes, leading to a faster or better immune response, particularly the development of neutralizing antibodies, which generally depend on T cell help. At the same time, pre-existing T cell memory could also act as a confounding factor, especially in relatively small phase I vaccine trials. For example, if subjects with pre-existing reactivity were assorted unevenly in different vaccine dose groups, this might lead to erroneous conclusions. Obviously, this could be avoided by considering pre-existing immunity as a variable to be considered in trial design. Thus, we recommend measuring pre-existing immunity in all COVID-19 vaccine phase I clinical trials. Of note, such experiments would also offer an exciting opportunity to ascertain the potential biological significance of pre-existing SARS-CoV-2-reactive T cells.”

    https://www.nature.com/articles/s41577-020-0389-z

    1. Derek Lowe says:

      It’s because you have all the hyperlinks in the comment – it goes into moderation until I get to it.

      1. Erik Dienemann says:

        Derek – thanks for clearing that up. Was driving me a little batty, lol, as I couldn’t figure out why sometimes comments were published immediately and sometimes after quite a delay.

  24. Erik Dienemann says:

    Testing…been having trouble posting comments since last night (and for weeks really)…

  25. bacillus says:

    Nucleic acid based vaccines have been around for a couple of decades now and none have been approved. They’ve been tried against several pathogens in clinical trials (e.g. flu), but have never been green-lighted by the FDA. Some of these vaccines elicited TH1-like neutralizing antibodies, and CD4 and CD8 T cell responses. Why do we think they’re going to work any better for SARs-CoV2?

  26. SALEH says:

    The corona pandemic in France is fading out . There seems to be a disconnection between virus circulation and mortality (Sweden for example) .
    One explanation is a much lower level of heard serological mass imunity needed to slow down the virus.
    Explanation: according to this recent publication using a different épidemiological modelisations ( based on heterogenism of population) the herd imunity needed is nearer to 25% than 70%. This seems to indicates that other factors are part of the game (either the virus or the host) explained here by Cellular type imunity (negativity of IgG in Poitive PCR persons in a cohort study in a confined german village)
    In another French cohort publication by cross resistance from other type of Corona virus .
    Taking these factors in account , il seems difficult to predict how a next corona pandemics will look like , and even if it happens at all (if yes then vaccine developpement might be the answer).

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