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Taking Two Different Vaccines?

We seem to be heading for a world with multiple coronavirus vaccines in it, and right off, I have to say that that this is a very good situation. But it has its complications, and one that I know many people have been wondering about is, what if you get two different ones? That could happen in several ways, of course, with the different vaccines themselves, the order in which a person is exposed to them, the total number of vaccinations involved, etc. And honestly, it’s not possible to be completely sure about the answer until this is actually tried (immunology!) But we can look back over previous vaccines and made some educated guesses.

The best outcome is that you get even stronger immunity. That seems to be what happens when people who received the oral (Sabin) polio vaccine were then given the injectable (Salk) form. The first is an attenuated live virus, and the second is a completely inactivated one. The Salk vaccine is better at producing humoral immunity (antibody and T-cell response), and the Sabin vaccine needs multiple doses to be effective. But it is better at producing mucosal immunity in the gut, which has a better chance of interrupting the spread of the disease in children. The choice about which one to use has always been a matter of argument. But the study linked above showed that in children who had already had the oral Sabin vaccine, that an injection of the Salk vaccine boosted their intestinal immunity better than another round of the oral vaccine. Again, you wouldn’t necessarily have predicted that – if it had come out that the injected dose didn’t seem to do much for mucosal immunity, it would have been easy to rationalize that as well.

There are other cases where multiple vaccines are available for the same pathogen, and where a mix-and-match approach doesn’t seem to make a difference either way. An example is hepatitis A, where there are several inactivated-virus options. In that case, it appears that the vaccines are basically interchangeable: the booster-shot schedule can be completed any way you like. The same goes for the two monovalent vaccines for hepatitis B, and for the three vaccines that target meningococcus group A, C, W, and Y. (Here’s an overview of vaccine interchangeability).

That said, all of those vaccines in each of those cases are rather similar to each other, and we now have the unusual – very, very unusual – situation of several different vaccine platforms coming into potential use against the same virus at almost the same time. By the spring we may well have two mRNA vaccines (Pfizer/BioNTech and Moderna), two different adenovirus vaccines (Oxford/AZ and J&J), and a recombinant protein vaccine (Novavax). We don’t have efficacy data on the J&J and Novavax candidates yet (numbers are on the way), and we can argue about the data for Oxford/AZ, but it’s certainly possible that all of them will be out there simultaneously. Putting one of these on top of the other is a step into the unknown.

And there are examples of vaccines for the same pathogen having some interference. Several vaccines for bacterial diseases are in the “conjugate vaccine” category: they have a bacterial polysaccharide fused to a carrier protein, which can give a more useful immune response than just dosing the polysaccharide by itself. But for pneumococcal vaccines, both types are given (with a different range of immune response to cover a variety of bacterial serotypes). It’s been found that if you give a pneumococcal polysaccharide vaccine (PPSV) followed by a pneumococcal polysaccharide conjugate vaccine (PCV), there’s a lower antibody responses for some serotypes targeted by the conjugate vaccine than there is if you give them in the opposite order. So the rule in this area is to give both for maximum protection, but to always give the conjugate vaccine first. Another tricky part is that the use of the same sorts of carrier proteins in different vaccines – you could imagine a situation where an immune response against the carrier protein causes a later vaccine to be less effective.

That last problem is similar to what we’re talking about with the immune response to adenovirus vectors and booster-shot dosing regimens with the same vaccine. But the Oxford/AZ vaccine is a chimpanzee adenovirus and the J&J one is Ad26, so that’s a different situation, and I have no idea of what would happen if you mixed those two. (The Russian vaccine is, in fact, a mixture of two different adenovirus vectors, one in the original shot and one in the booster). I also don’t know what happens if you take both an mRNA vaccine and one of the other types.

Overall, though, I would tend to think that it would work out. All of the coronavirus vaccines we’re talking about target the Spike protein, after all, and they are, by different means, presumably raising a pretty similar suite of antibodies (with perhaps more differences in T-cell response, which remains to be seen in detail). So the chances are that the immune response will be similar (as with the hepatitis vaccines) or perhaps even a bit better (as with mixing the polio vaccines), rather than worse. But we haven’t proven anything like that in the clinic yet, and educated guesses will only take you so far. I would assume that there will be people who end up taking both types, for all sorts of reasons, and I hope that we collect as much data from those cases as we can.

106 comments on “Taking Two Different Vaccines?”

  1. Hanno says:

    While reading that I had a related question that’s maybe even more important:
    What happens if a person who already was infected gets vaccinated? (Though I probably can guess the answer: It’ll probably work out fine, but we don’t know.)

    I assume this is almost inevitably going to happen, as it seems to be generally assumed that many people are infected with little to no symptoms and there are likely many people who were infected and don’t know.

    1. Marko says:

      ” What happens if a person who already was infected gets vaccinated? ”

      My question is different , though related : Why would we immunize anyone in the early vaccine rollout who has been infected , given they likely have protective immunity already , and given that we don’t have nearly enough doses to address all of the high-risk population ? The CDC estimates that up to 30% of the US population may have been infected to date. A sensitive antibody test ( perhaps even a rapid test ) before vaccination could detect the vast majority of those , saving the limited vaccine supply for those truly in need.

      1. Oudeis says:

        My suspicion, which may be totally wrong, is that the added expense and logistical difficulty involved in running tests before the vaccinations would outweigh the benefit.

        And then there are the inevitable errors in the process. Do you want to be someone who doesn’t get the vaccine because of a false-positive antibody test? Or who doesn’t bother to get tested because you’re incorrectly sure you already had it? There could be millions of those people, depending on the quality of test you use and how long you make previously infected people wait to get vaccinated.

        Again, I don’t know anything, but it seems better to me just not to worry about it.

      2. M says:

        30% would suggest about a 7-8x true infection rate vs. known infection rate. ~100MM people in the US already infected if true.

        1. if this is true, then the infection rates should very soon begin declining

          1. Francis Banks says:

            I think you should take a look at what is happening in Manaus, Brazil. It has recently been estimated that 76% of residents have been exposed to the virus, and yet the infection is still out of control, with healthcare systems collapsing.

      3. An Old Chemist says:

        In the early experimental trials, it was reported that vaccination gave rise to a higher titer of antibody and T-cells than were present in the bodies of people who had acquired such antibodies through natural infection. A higher titer is required for a long-term immunity and to ward off chances of a re-infection!

        1. Marko says:

          We know from real-world data that immunity acquired from infection protects against re-infection. We have yet to see the proof of protection from infection by vaccines. The seropositivity results from the vaccine participants will tell us that , but that info hasn’t been released yet to my knowledge.

          In any event , long-term protection for those who’ve already been infected is not the issue. In just a few months , sufficient vaccine doses will be available to cover all high-risk patients , including those who may be tentatively labelled “high-risk” but have been infected previously.

          Potentially , 50-100,000 deaths/month from Covid-19 will occur in the next few months, many of which can be prevented if we can get the vaccine to those who are truly high-risk , which does NOT now include those previously infected. The fact that we don’t have a vaccine-sparing strategy for rollout to avoid wasting shots on the already-immune is a travesty , but hardly surprising.

          1. Chris Phillips says:

            I assume your comments relate entirely to the USA.

            I shudder to think how long it is going to take to vaccinate all the people most at risk in the developing world, and I find offensive some of the comments I’ve read about people luxuriating in as many different vaccines as they can grab.

            However, I can see that it may make sense to vaccinate those most at risk with one vaccine first and another later, if availability dictates that (for example AstraZeneca first, and Pfizer/BioNTech later).

    2. Matt says:

      I was surprised to see no mention of previous infection in the CDC framework for who should receive the vaccine first yesterday. I’ve heard speculation that the vaccine could provide better immunity than infection, but even so our path to herd immunity is much faster if we limit overlap of vaccine receipt and previous infection.

      1. Aleksei Besogonov says:

        I guess it just doesn’t make much difference practically (only around 5% of the US has been diagnosed with COVID – for now). And testing included people who recovered from COVID, so safety is apparently OK.

          1. M says:

            I see I’m late to the party.

      2. Bill says:

        If indeed 1/3 of the country has actually been infected then it would certainly make progressing through the upper risk categories faster from a dose availability aspect. Just include the previously infected into the normal risk group at the end.

        1. Marko says:

          On twitter , Dr. Paul Offit is quoted as saying the main reason we don’t do this is the logistical challenge.

          In other words , we can’t get our shit together. Yep , that sounds about right.

        2. M says:

          I’ve read (CDC, modeling estimates from a group in Australia) that the true infection rate is anywhere form 3x to 25x the known rate, depending on country. This is a truly difficult number to pin down with any accuracy. I think most people understand that the true infection rate is higher than known case infection rate but just how much higher?

          My speculation is that it’s substantially higher, possibly close to 10x, and that is why we are lately seeing the spread/spikes in rural and not just industrial areas. So many asymptotic people have it, don’t know they have it, and are unknowingly spreading it. Many of them are probably 20-30 somethings. I think when bars/restaurants are shut down and we see these corresponding decreases in case numbers, this is why.

          1. Thomas says:

            But it seems that asymptomatic (or low-symptom, for that matter) infections do not raise much of an antibody response.
            So these cases will likely benefit from vaccination.

          2. David Chase says:

            You can plug some of these hidden infection estimates into observed infection rates in places like NYC — generally, the total population is an upper bound on how many people can be infected, which in turn gives a bound on how many undetected infections there are per observed case. Some cities in Massachusetts (Chelsea, e.g.) have already been hit very hard, yet the “second wave” seems to hit just as hard there, as if the number of people who’ve been infected (at least, well enough to acquire immunity lasting 8-9 months) is not that large at all.

    3. Valdis Andersons says:

      The booster effect of the vaccines can be immense after a wild type infection. (fig 6)

    4. Stu West says:

      I can’t link directly to it, but CNN quotes Dr Ozlem Tureci of BioNTech as saying the vaccine trial included people with prior infection status, and that there was no difference in the safety profile for that group. When the vaccine rollout happens, some people who already had Covid are bound to get the shot, so it’s good they took that into account in the trial design.

      1. debinski says:

        As a subject in the trial I can verify that it included people who had covid previously who didn’t know it. We received the first vaccine on day 1, the same day they took PCR nasal swabs and blood for antibodies (without knowing the results of testing). Their primary efficacy endpoint is based on subjects who were not exposed to covid prior to baseline but then there is a secondary endpoint that includes all subjects regardless of baseline status. No doubt they are taking advantage of the previously exposed subject group to look at safety.

        1. debinski says:

          *infected not exposed

          1. guneapig says:

            At the Pfizer trial, IIRC if you tested positive for antibodies at the first shot (blood taken concurrently with shot, so you get the first one anyway, after an in-person health review), or caught COVID along the way before the 2nd shot then they wouldn’t give you the second, but asked you to remain in the program.

    5. Brit says:

      From the UK vaccination programme guidance:

      There is no evidence from clinical trials of any safety concerns from vaccinating individuals with a past history of COVID-19 infection, or with detectable COVID-19 antibody so people who have had COVID-19 disease (whether confirmed or suspected) can still receive COVID-19 vaccine. This is because it is not known how long antibodies made in response to natural infection persist and whether immunisation could offer more protection. If antibodies have already been made to the disease following natural infection, receiving COVID-19 vaccine would be expected to boost any pre-existing

      1. BDBinc says:

        There are no such thing as “covid” antibodies, how did you distinguish the antibodies from Sars Cov( 2002) or the corona virus .
        You did not you just assumed from the (now court struck out as ) PCR test that they had ” covID” the antibodies are the same for Sars CoV.

        Still waiting for someone( with the ability to reason) to admit that not all infected people have antibodies and that having antibodies does not prove immunity .
        In fact last time I checked science did not know if having antibodies it means you had an infected, currently have an infection or are immune.
        Your innate immune system does not always create antibodies.

        I am concerned that the science is forgotten and its fear, ignorance and consensus beliefs that are at work.

    6. Tracy Kolinger says:

      61 years old with a garden variety (thyroid) auto immune disease. I also have moderate asthma. For the last 40 or so years I’ve had a flu shot and still probably have had the flu maybe 8-10 times. Generally I get 3-5 respiratory infections per year. This masked year of staying home has been my healthiest in over a decade. I’m on every list to get vaccinated and I will get whatever is offered. However, and my provider agrees with me, if I get the J & J first I will try and pursue an mRNA vaccine as soon as it becomes ethical to do so. That probably means as soon as most people who want some kind of vaccination have had a chance to get it. My spouse, is 72 with no health issues has just had a second Moderna shot.

      Meanwhile I’ll continue to stay home and have groceries delivered to the trunk or doorstep. I’d sure like to know where to sign up for a trial to get both types of vaccine’s.

  2. Walter Sobchak says:

    I am 73 and have hypertension (weel controlled). I am going to tak every vaccine I can lay my hands on when and where I can get them. And i will lie and cheat to do so. Only a gun to my head will stop me.

    1. Marko says:

      ” I am 73 and have hypertension (weel controlled). ”

      I’m assuming you misspelled “weed”. That’s interesting. Do you smoke it or take medicinal THC?

      1. Walter Sobchak says:

        No. I misspell well

        1. Marko says:

          I was kidding. I can’t pass on a good straight line.

      2. David says:

        Perhaps the type was intended as “well”. The other option is more entertaining though!

        Thanks for the continued updates Derek. Your insights are the first tab on my daily info checks.

    2. Why do people like you existYou sound like Trump..lie ..cheat..steal…

    3. So nice to lie, cheat, and steal.You must be Trump.

  3. Valdis Andersons says:

    Make my mix J&J or AZ/Oxford as the prime and Novavax as the boost:

    It looks to be a similar effect that the polio vaccines have, the live attenuated primes all the right parts of the immune system and the protein/inactivated gives it a good kick (maybe due to the adjuvant?).

  4. ScientistSailor says:

    If you were going to take two vaccines, wouldn’t you want them to be against different epitopes? The first 3 are spike only. What’s the status of an inactivated virus vaccine?

  5. MTK says:

    I’m going to stick to what’s been proven clinically.

    90-95% efficacy and some known safety signal sounds better than untested efficacy and safety signal. Even if some mix was better there’s not a lot of room for improvement here seemingly.

  6. Marko says:

    Imagine looking at this CDC graph and then arguing that somehow we’re mixing up flu and Covid cases , and inflating the impact of the latter :

    Yet that’s exactly what the denialist Magatards do , over and over. To be fair , some fraction of them may have a legit excuse : post-Covid brain fog.

  7. exGlaxoid says:

    If I start with the AZ/Oxford vaccine (in a study) I wonder if getting even one dose of Pfizer or Moderna vaccine would put me at 95% efficacy? They did say that at the end of the trial, they would give placebo patients the real vaccine, but I might prefer the Pfizer one in that case. I suspect that would not be an issue, but may get to find out in a few months. I don’t see any reason to think that taking multiple vaccines would be an issue other than building antibodies to the viral vectors.

  8. steve says:

    The polysaccharide story is not really analogous to the two coronavirus vaccine scenario. The reason you need a carrier for polysaccharide conjugates is to provide T cell help as sugars are generally pretty weak immunogens and generally only invoke T cell independent antibody responses. Those responses often don’t drive much in the way of memory. What might be happening in the scenario you mention is that the T cell independent immune response is inducing some tolerance to the subsequent T cell-dependent response because of the weak nature of the initial response. It is doubtful that would happen with the current adjuvanted vaccines that provoke very strong immunological responses that include T cell help

  9. Steven Sandler says:

    Thanks for the article. I am glad you mentioned Mucosal Immunity and an Oral form as that is what Vaxart’s pill is shooting for in their clinical trials. Early results are very promising and as a differentiator their pill delivered through the gut is targeting the S and N Proteins. They’re just finishing the Phase I and quickly progressing forward. Interested to hear your thoughts.

  10. vv2 says:

    Something I have been wondering about for a while is if there would be any risk in vaccinating a patient who had active Covid at the time (presumably asymptomatic, or confused the symptoms for a common cold). My concern is that Covid has a tendency to send the immune system into overdrive, which is responsible for as much damage as the virus itself. Perhaps the patient’s immune system is managing to maintain the proper balance, clearing the infection without attacking endogenous cells, but then this patient receives a vaccine shot that send the immune system into overdrive and triggers a cytokine storm. Worth worrying about?

    1. Brit says:

      From the UK vaccine programme guidance:

      People currently unwell and experiencing COVID-19 symptoms should not receive COVID-19 vaccine until they have recovered. This is to avoid wrongly attributing any new symptom or the progression of symptoms to the vaccine. As deterioration in some people with COVID-19 can occur up to two weeks after infection, ideally vaccination should be deferred until they have recovered and at least four weeks after onset of symptoms or four weeks from the first PCR positive specimen in those who are symptomatic. There is no evidence from clinical trials of any safety concerns from vaccinating individuals with a past history of COVID-19 infection, or with detectable COVID-19 antibody so people who have had COVID-19 disease (whether confirmed or suspected) can still receive COVID-19 vaccine. This is because it is not known how long antibodies made in response to natural infection persist and whether immunisation could offer more protection. If antibodies have already been made to the disease following natural infection, receiving COVID-19 vaccine would be expected to boost any pre-existing antibodies.

  11. Jason P says:

    Thank you Derek, THANK YOU!

    Very timely reporting and very useful information as we move into the phase where several vaccines are available.

    On a side note, the news is reporting that freezers capable of the – 90-degree storage were just installed and wired in to the local hospital and they expect to be getting doses soon!

  12. En Passant says:

    Thank you Derek for this timely and informative post.

    I am not a chemist or medical professional, pharma or otherwise. So, please bear that in mind if you choose to answer this question.

    I am puzzled by one issue you raised above:

    The best outcome is that you get even stronger immunity. That seems to be what happens when people who received the oral (Sabin) polio vaccine were then given the injectable (Salk) form.

    The historical fact is that the Salk form (introduced in 1955) was widely used before the Sabin form was introduced in 1961. I distinctly recall receiving the Salk injection in the 1950s and the Sabin oral vaccine in the 1960s.

    The situation you described is the reverse of what a likely large cohort of people experienced.

    So, my question: Did receiving the Sabin vaccine after the Salk convey a stronger immunity like the reverse situation that you described?

    Or is there even any data with which to answer that question?

    1. Charles H. says:

      IIRC, taking the Salk vaccine first and then the Sabin was not only safe, but was reported to be safer than just taking the Sabin. I’m certain I was told that the Sabin vaccine produced a more durable immunity, and there were reports of some bad results (what? well, it’s been decades) among those who only got the Sabin vaccine, but not among those who had first had the Salk vaccine. The bad reactions were rare. I have a vague memory that some of the people who only got the Sabin vaccine got an active case of polio from it, but the memory it too vague to be trusted.

      1. 이웅견 says:

        Oh, I seem to remember a horrible mishap with the Salk vaccine, not the Sabin one.
        You can search for “Cutter Incident” or check or

  13. Ron Schnell says:

    In the lab phases of Pfizer and Moderna there was some talk in here about Pfizer having better T-Cell efficacy than Moderna (I think Pfizer had good CD4+ and CD8+ but Moderna had more one than the other). I haven’t seen any talk of this post-lab. Do we know anything about whether or not we still think this is the case, and what (if any) this will do to short-term and long-term efficacy?

  14. Adrian says:

    I am surprised you are not even mentioning the Sinovac vaccine, which is a platform different from the vaccines you mentioned (inactivated virus).

    While the current premature approvals of various vaccines by governments in China/Russia/UK is a valid concern, this does not imply that the approved vaccines are not working.

    Sinovac is expected to publish phase 3 efficacy data from a trial in Brazil within days, and looking at contracts by countries in Asia and South America it might end up being the most widely used vaccine in the world.

    1. Barry says:

      SinoVac seems to have changed their inactivation protocol and proceeded straight to Phase II clinical (efficacy) trial w/o a Phase I (safety) trial for the new prep. That doesn’t mean that an inactivated virus vaccine–or even this inactivated virus vaccine–can’t work. But it does set it back at least WRT FDA. FDA’s first commission is Safety; efficacy is secondary.

      1. John Hasler says:

        While skipping phase I seems unethical surely phase II cannot help but provide the same daa.

      2. Adrian says:

        FDA approval is not relevant for 95% of the worlds population, and it is not clear whether they will apply for approval in the US at all. I do fully agree with you that countries like China or the UK should have focused more on safety instead of the rushed vaccine approvals they did.

        In practice the Sinovac vaccine is in competition for the first COVID-19 vaccine administered to 100 million people.

        And taking two different vaccines might become a very relevant topic if travel restrictions will mandate different vaccines as prerequisites for entering different countries – imagine the Biden administration would require a vaccination with an FDA approved vaccine for being allowed to enter the US, while the Chines government requires a not FDA approved vaccine for entering China.

        1. A Nonny Mouse says:

          How do you know the approval is “rushed”? The authorities have been working with Pfizer since June and reviewing data as it came in. The final documentation was presented at the beginning of November, so that’s a month for review.

          Interestingly, the WHO has asked for all of the documentation in order that they can use it for getting approvals in other parts of the world which are unable to conduct the work themselves. I am sure that they will discover anything untoward.

          1. Adrian says:

            Here in Europe everybody knows that the UK rushed the approval because the populist from New York with the prominent blond hair who is Prime Minister of the UK has horrible poll numbers and a Brexit four weeks ahead with no agreement yet.

            The European Medicines Agency as well as pretty much everyone in the EU is not shy about criticizing the additional risk the British government is taking with this premature approval:

          2. Lambchops says:

            Concur with A Nonny Mouse when it comes to the UK perspective.

            The folks at the MHRA are very much the same people who have been heavily involved in EMA decisions for years and years – they’re heavily experienced in this type of work and there’s no reason that they can’t speed up timelines a little in the face of an emergency.

            Ignore the nationalistic political grandstanding from the likes of Matt Hancock (who should know better) and Gavin Williamson (who quite clearly doesn’t). I wouldn’t be surprised that (within the confines of what they are able to share) the regulators across various countries are helping each other out in what is a time of great need rather than engaging in some meaningless pissing contest about who is “first” and “best.”

          3. Adrian says:

            I trust the European Medicines Agency that they know what they are doing when they say they need another 4 weeks for approval, and the public statement from the European Medicines Agency that the British approval is not appropriate.

            With the European Medicines Agency being responsible for approvals in the EU, the MHRA did not have much authority for approvals in the past.

            I am sure the European Medicines Agency would also speed up timelines if this was possible without sacrificing safety, and they surely had to withstand political pressure to approve faster.

            This is not a pissing contest, this is reckless approval for political reasons.

          4. Lambchops says:

            I absolutely trust the EMA’s words too – if they say they need more time, they need more time.

            However, although I’ve expressed worries here in the past about the political pressures the MHRA might face post-Brexit (a certain Alzheimer’s drug with dubious efficacy data springs to mind!), I do still tend to trust the MHRA’s words. The current head was quick to act on safety concerns with valproate use in pregnant women (another example, if I recall correctly, where the MHRA made final decisions around a month in advance of the EMA – so there is precedent for this sort of thing) and doesn’t seem like the type to bow to political pressure.

            If corners were cut in a dangerous fashion then this will come out and I’d be among the first to be critical.

          5. Wilhelm Cody says:

            Why should a review of a product take 10 days or 40 days or 160 days or whatever? Here are some factors that can affect the time for review.
            1. Where is the review in the queue? Normally a product would have to get at the end of a line waiting for other products to be reviewed. In the case of a pandemic the product goes to the head of the line and everything else that might take away review resources is put to the side.
            2. What are the resources brought to bear? Normally a product would have a limited team from various departments looking at the filing. These teams might review features in series rather than in parallel. With these vaccines, any regulatory agency should be doing everything in parallel or even before submission. Examples include plant inspection, review of design and preclinical data, etc. One sign that this has occurred at least in the USA is the change by the FDA in acceptance criteria for interim and final looks. Another example is setting up the advisory review meeting in advance. The FDA had a meeting arranged around the 10th of December well before submission based on a UCSF MedCram video.
            3. How long does review actually take? Statistical review and review of safety probably take the longest . Completion is necessary before the internal meetings and debate. In the case of the trials, the statistical review protocols should have been set in place well before submission and many internal discussions should already have uncovered hypotheses of issues to be considered. Pfizer should have shared with the FDA detailed data from the preliminary look so the final filing is not strange. At the lease staff would be expected to be working 7 days a week until their section is completed.
            4. How good are the data? Messy data take longer to review. Clean data should be faster. Hopefully Pfizer provided clean data with no hints of obfuscation or re-categorization. Hopefully, reviewers rapidly identified potential issues and speedily sent letters to the company and equally rapidly reviewed their replies. Hopefully, Pfizer provided clean information in the replies. Certainly having a signal well above the minimum necessary will help review. Moderna should be in the same situation. Frankly, AstraZenica/Oxford data will take much longer even with good preparation give the lower response rate and the kerfuffle in the British arm of the trials plus any effects on dosing schedules from the longer delays in the USA arm of the trials.
            5. How does politics affect the situation? Politics is the art of the possible. If a government has citizens dying at a rate well above average, it is possible to do things faster if that is your number one priority. If they care more about differentiating themselves from those with whom they disagree or even despise, then they might want to appear more diligent or formalistic even at the potential expense of the citizenry. It is up to the citizens to then decide which is the better approach.

          6. Druid says:

            After the Brexit vote, the EMA was moved to Netherlands from London is quickly as possible and all the UK rapporteurs who until then had been major contributors were kicked out. As a result, the UK assessors have had time on their hands and were free to read the vaccine submission(s) while the EMA has had too much work to do, causing major delays in reviews. Unlike other scientific organizations, the EMA behaved irresponsibly in response to Brexit and is now paying the price. I suspect the HQ only went to Utrecht because otherwise the French and Germans would still be squabbling over it 4 years on.
            This is from the EMA website: “For EMA, this means that as of 1 February 2020, no one who represents the UK, or is appointed or nominated by the UK can participate in any EMA scientific committee meeting, working party meeting or in the Agency’s Management Board.” Thanks, EMA!

  15. johnnyboy says:

    One thing no one seems be mentioning, and that I would have expected by now when the cheering has subsided, is that 95% protection means there would be 5% of vaccinated people walking around thinking they are protected when they aren’t. That’s millions and millions of potential superspreaders. If the entire population was vaccinated at the same time this wouldn’t be too much of an issue, but vaccination will likely be spread out over months, so the unvaccinated might be exposed to a greater number of infected people than they are now, especially since social distancing measures are bound to become more lax because of the false sense of security that the availability of vaccines will cause.
    Clearly we need some way of predicting or detecting vaccine non-responders, but I’m not seeing any mention of this anywhere. Are we in line for a 4th wave in the spring ?

    1. Adrian says:

      It is even worse than that:

      The way the trials were designed, it is not known whether the vaccines do actually lower infections and transmissions.

      These numbers are reductions in symptomatic infections, and the data also indicates that the people who did develop symptoms despite vaccine only developed mild COVID-19.

      This would be consistent with fewer infections, but it would also be consistent with no reduction in infections at all reducing only the symptoms for infected people – turning symptomatic people into asymptomatic superspreaders.

      1. Mariner says:

        Even if everybody vaccinated becomes asymptomatic, potentially being able to spread the virus without realising they were infected, providing the most vulnerable can be vaccinated relatively quickly, we’ll still see a great reduction in deaths and other serious outcomes.

        As others in this thread have noted, the indications are that asymptomatic carriers don’t spread the virus a great deal and there is some (though scant) evidence that the vaccines can also reduce asymptomatic infections.

        Providing the vaccines prove to be safe and can be rolled out to the general population quickly, I can see the pandemic curve being quickly flattened in the developed countries and then hopefully elsewhere relatively soon thereafter. Even if the disease is running rife, if the harm it does is greatly reduced then it quickly becomes less of a problem for all but a few.

        How long immunity/resistance may last is a different matter and something we can’t know for some time. You’d assume that work on treatments for the virus will continue apace as well as faster and more accurate tests so in the future, it may end up being a matter of visiting the doctor if you’re feeling unwell, receiving immediate treatment if testing positive and then isolating for a period of time. You’d have to assume that quick contact tracing for those will be taken seriously by governments wishing to avoid the more serious problems caused by the pandemic.

        All we need to do is get the R0 rate below 1 and keep if there and this initial hit of the pandemic will end. Historically, we know these serious pandemics tend to have serious effects for a few years but the scientific advances we have in the modern era mean that vaccines may be able to reduce this to a single 12 to 18 month hit.

        Of course, it would be nice if there some sterilising immunity was possible, in which case the R0 will quickly drop a long way below 1 and we’ll be in a position to plan for a resurgence in the future, providing immunity doesn’t last.

      2. theasdgamer says:

        “‘No evidence’ that asymptomatic Covid-19 cases were infectious, analysis of post-lockdown Wuhan concludes”

        The asymptomatic superspreader myth refuses to die.

        1. Irene says:

          Individual asymptomatic people don’t appear to have been superspreaders. But if you have lots of asymptomatic people causing a little spread each, that’s a lot of spread. Also, some PRE-symptomatic people DO cause a lot of spread, and ambiguously symptomatic people (e.g., just a bit of a cough that could be from anything) probably even more.

    2. Michael says:

      I don’t even know where to begin with this kind of extreme pessimism, so I’ll respond in point form and in no particular order.

      * Your “5% of people walking around thinking they are protected when they aren’t” construct is not correct for a few reasons. The trials have demonstrated that the number of people symptomatically infected is 95% lower than the number of people symptomatically infected in the placebo control group, so this says nothing about cross-protective immunity from other coronaviruses or, indeed, natural immunity from past infection. It’s a 95% reduction of susceptibility, not a straight-line lottery system where it does nothing for 5%.

      * There is no reason to think that those in the trials with symptoms were “not protected,” given the reduction in severe disease (100% so far with Moderna). Immunity is on a spectrum and partial protection is a thing.

      * In contrast, “asymptomatic superspreaders” is likely *not* a thing. Infectiousness is highest within the five day period immediately before and shortly after symptoms develop. Pre-symptomatic spread is more pronounced than asymptomatic spread, and the secondary attack rate of asymptomatics is currently estimated as 2/3 less than symptomatics. In any event, not every transmission is synonymous with “superspread” and this term should be used carefully.

      * There is every reason to think that the amount and duration of asymptomatic shedding will be reduced, if not eliminated, through the protection provided by vaccines. Pfizer/Moderna showed this in animal trials. Novavax (and I believe one J&J animal experiment) had zero shedding in animals. And these are with challenge doses of the virus.

      * You can’t project forward pandemic conditions with exponential growth in a world where the vast majority are naive to the pathogen into a world with significant population-level immunity through immunization and infection. The more immunity, the less explosive the growth. The more immunity, the less opportunity for “superspreading.”

      * I strongly disagree that the data is “consistent with no reduction in infections at all.” If there were no reduction in infections at all, there would be no protection of the upper respiratory tract. And because there are upper respiratory symptoms that would count as a fail in these trials (loss of taste/smell, for example), it just doesn’t make sense to infer that there were an equal number of infections in the vaccine group and the placebo group. They will test the group for new N antibodies to see if there have been asymptomatic infections, but most predict that they will have been substantially reduced.

      1. johnnyboy says:

        “so this says nothing about cross-protective immunity from other coronaviruses or, indeed, natural immunity from past infection”
        Not quite sure what your point is. We know nothing of cross-protective immunity from other coronaviruses. In any case it is not relevant to the 5% susceptibility to infection post-vaccine (as clearly these 5% were infected, despite the putative presence of cross-protective immunity).

        “There is no reason to think that those in the trials with symptoms were “not protected,””

        Well they got the disease, so they were not protected from infection. They got milder disease, great for them, but that doesn’t mean they were less infective to others, which is what I’m talking about here. Indeed someone with milder or borderline asymptomatic infection is a greater risk to the unvaccinated than someone with severe disease who is hospitalised.

        ” In contrast, “asymptomatic superspreaders” is likely *not* a thing. Infectiousness is highest within the five day period immediately before and shortly after symptoms develop.”

        Do you see how these two sentences contradict each other ?

        “You can’t project forward pandemic conditions with exponential growth in a world where the vast majority are naive to the pathogen into a world with significant population-level immunity through immunization and infection”

        My point was that it will take months before we reach that world with significant population-level immunity, because of the logistical difficulties in vaccinating millions of people (twice). It is that period that I am concerned about.

        1. Michael says:

          But it isn’t the case that 5% of the vaccinated cohort got infected, or even that 5% are necessarily susceptible. Rather, it is the case that the number of infected in the vaccinated group was 95% lower than in the placebo group. What we know is that 19 out of ~37,000 people to get the actual Pfizer or Moderna vaccines acquired symptoms — not that 5% of the 37,000 were running around super-spreading. We also don’t have the data yet to see if any comorbidities are correlated with the 19 who came down with symptoms, which might help guide prioritization of rollout.

          Obviously, there is no contradiction between saying that there is a difference between asymptomatic superspread and presymptomatic superspread. By definition, only 19 of those who received the Pfizer/Moderna vaccines were ever presymptomatic.

          You speculate that vaccine protection “doesn’t mean they were less infective to others,” but the animal models, the efficacy numbers and common sense all suggest that someone with a robust antibody and T-cell response will shed less infectious virus than someone seronegative pre-infection. I predict that there will be a significant difference in shedding between the asymptomatic-but-infected vaccinated group and asymptomatic infections among the unvaccinated — and we already know that asymptomatic spread pales in comparison to presymptomatic or symptomatic spread.

          1. Michael says:

            I’ll correct myself by saying the number of symptomatic cases was 95% lower, and I misspoke by saying the number of infected was 95% lower. But otherwise I stand by my points.

            More evidence of much lower attack rates among the asymptomatic:


          2. Adrian says:

            This study is on people during the early times of COVID-19, when people considered symptomatic COVID-19 a normal cold where your employer would fire you if you’d take that as an excuse for a sick leave.

            In most developed countries everyone with slight cold or flu symptoms gets immediately tested for COVID-19, and for confirmed infections contacts are traced. People with symptoms are no longer a substantial source of further infections.

            Asymptomatic and presymptomatic spread has been the problem during the past 9 months, in many places the first positive COVID-19 test uncovered a cluster with a 3 or 4 digit number of people.

            The vaccine trials were not designed to get any data on asymptomatic carriers or virus shedding of asymptomatic people.

            I remember a monkey study with the Oxford vaccine where all monkeys were protected from serious lung damage, but from the virus levels in the upper respiratory tract a PCR test would have returned positive.

            I am worried we might be seeing the same in humans.
            I hope I am wrong on that, but there is no data to show either way right now.

          3. Michael says:

            Adrian, I agree in part and disagree in part. Most transmission is still in the household, where “staying home” obviously does not eliminate symptomatic transmission.

            The trials will do blood tests of the participants to check for nucleocapsid antibodies that will reveal whether a natural infection occurred after the vaccine was administered. It’s hard to use that data to make conclusions about shedding because individual immune responses are so diverse.

            I agree that the Oxford monkey study showed upper respiratory infection. I think the mRNA vaccines will do far better than the Oxford vaccine on that front and I am less confident that the Oxford vaccine will reduce asymptomatic shedding (but they claim that the early data shows it does). That said, the Oxford study used by far the largest viral challenge dose.

            Also, in mice experiments, the wild-type Spike sequence like the one used in the Oxford vaccine was less successful at preventing upper respiratory shedding than the mutated Spike sequences used in Pfizer, Moderna, J&J and Novavax. Who knows, but that could be another differentiating factor.

          4. Adrian says:

            Inside a household of 4 people the worst case for symptomatic transmission would be R = 0.75, and no one outside the household gets infected from that. This is a dead end for the virus.

            For the effects of asymptomatic transmission by vaccinated people we simply have to accept that we do not yet have any data on that. My worry is that there might be a huge problem, and your hope is that there is no problem. Both sides have valid arguments, neither can be excluded without human data on that.

          5. Michael says:

            With all due respect, Adrian, I don’t see valid arguments that the mRNA vaccines have no effect on infection and transmission.

            There’s value to having an abundance of caution, value to managing expectations, and obviously value to professing uncertainty about things that aren’t yet proven. Fine. But there is no evidence of which I am aware that can lead anyone to the conclusion that it is likely that the mRNA vaccines are simply converting people with symptomatic disease to infectious asymptomatic carriers. There just isn’t any.

            This does a good job assessing the null hypothesis of no URT protection for the Pfizer vaccine:


          6. Adrian says:

            This whole field is full of theories that sounded plausible but turned out to be wrong, and someone writing something on Twitter is not exactly scientific proof for anything.

            But it is funny that even the claims from your Twitter guy support my worries:
            “Simplistically, then, there might be 32 asymptomatic cases in the vaccine arm, and 8 symptomatic. Compare that with 162 symptomatic infections in the placebo arm + another estimated 30 asymptomatic.”

            Note how your guy states that there might have been more asymptomatic cases in the vaccine arm than in the placebo arm.

            Which is exactly my worry.

          7. Michael says:

            Read on to the next tweet:

            The math doesn’t add up if there were no protection in the URT. I think the difference has to made up by 1) memory cells/Abs that sharply limit the virus and shedding before symptoms arise and/or 2) sterilizing immunity. In both cases that is good for onward transmission.

            The immunologist/”my guy” has also been recently published in Cell, if that impresses you more than Twitter:


    3. M Welinder says:

      I wouldn’t worry over the 95% number.

      Those 5% which, for simplicity, we can say aren’t protected at all will meet far fewer infected people and, if they become infected, will themselves meet far fewer people to infect. If the average number of new people infected per infection goes below 1 for a while, the epidemic is over fast.

      Unless… there are concentrated pockets of non-vaccinated people large enough and connected enough to be their own little world. the usual gang of idiots, in other words.

      1. Adrian says:

        Unless… many people who do not even suspect they might be infected become asymptomatic carriers, and the usual gang of idiot politicians allows bars and restaurants to reopen before the epidemic is officially declared over.

        South Korea had a second wave in spring after one infected person spend a night partying in a few gay nightclubs in Seoul. This person had 1300 contacts and infected over 100 people in one night.

        The vaccine trials were not designed to gather data on whether they reduce R, we simply do not know for certain whether vaccinated people are actually protected from infection.

        1. Valdis Andersons says:

          Actually, Oxford did check for just that. They noticed a reduction of asymptomatic infections in the vaccine arm(s). You can read that in their official statement (4th bullet point):

          1. Marko says:

            Thanks for posting that link. I missed that one. It’s the first hint of the data showing reduced transmission that I’ve seen. A good sign , even if it is what most expected.

            Can’t wait to see the actual numbers….

  16. Bill says:

    Assuming there were 5% of unknowing vaccinated but infected people, that would only be in addition to the unknowable number of anti-vaccers and Covid deniers and others who for any number of reasons haven’t gotten their jabs. Whatever it is, it will have to be lived with.

    Different subject — a question. Is there a planned or designed difference between a 1-dose vaccine and a 2-dose vaccine? Or is the 1-dose sufficiently superior that it’s good to go, and the 2-dose doesn’t quite get the job done first try and needs a booster to compete. Otherwise similar.

    1. Some idiot says:

      I’m not an immunologist, but in the earlier phases of clinical trials, they all tried both single and double doses. However, most of them found that a single shot did not give “appropriate” levels of antibodies, so they went with the booster in Ph3 (J&J being the exception).

      “Appropriate” means levels that looked superior to those from patients who had recovered from an infection.

  17. Bacillus says:

    Regarding polio vaccines: Because the Sabin vaccine can revert to a fully virulent form of the virus (and is now the most common cause of polio rather than wild-type virus), current practice is to vaccinate with Salk vaccine first followed by the Sabin vaccine. The idea is that the former will prevent infection if the Sabin vaccine reverts. The real beauty of the Sabin vaccine is that it is shed fecally for quite a while afterwards allowing oro-fecal transfer of the vaccine to close contacts, thereby boosting herd immunity. Indeed, this is probably why polio is now on the edge of extinction in the wild.

  18. exGlaxoid says:

    I’m not a doctor, but I cannot see any way in that lowering the number of symptomatic cases of Covid will not drastically reduce the effects of Covid on humanity. If the people who get the shot have a 95% lower chance of getting symptoms from being sick, I cannot believe this will not eventually lower the transmission of the illness. I understand that we don’t have real data yet on that, but if you can just reduce the number of people over 65 from getting sick enough to go to the hospital, you would drastically lower the number of hospitalizations, deaths, and pain from Covid.

    I think that once we can get the bulk of the older people vaccinated, there may still be cases, but the deaths will drop and once other people see the reduction in sickness and hopefully the lack of side effects from the vaccine, more people will be likely to get the vaccine. Since the anti-vaxxers and anti-maskers seem to be similar people, they can choose to take their chances, and that should be their right, but many schools, work places, resorts, ships, and government agencies will eventually require vaccination to attend, so that will eventually drive the vaccination some also.

    Eventually most people will get immunity from either a shot or from the disease, given the virulence of Covid, but if we can lower the number of deaths and hospitalizations, that will allow us to go back closer to normal. I just hope that people will see that vaccines work and the number of anti-vaxxers will finally start falling, but if not, nature will take care of that for us.

  19. DCSZ says:

    How well protected will people be against the Sars-Cov-2 virus after the first shot? It seems very likely that there will be people who get the first shot of the vaccin (either Pfizer/BioNTech´s vaccin or Moderna´s vaccin) and get infected in the period before they are able to have the second shot.

  20. DataWatcher says:

    I’m more concerned about people taking only one shot.

  21. BDBinc says:
    Its 11 months later ( I’ll pretend its not the flu and say )everyone’s been exposed with their uncovered eyes and 1/4 inch (gaps in face masks ) .Big pharma profits greatly off this vaccine, already over $10 billion taxpayer funds just for development in the US alone.

  22. JDPatten says:

    Has interaction between the Zostavax and the Shingrix vaccinations been investigated?
    I got both – each as they were approved. ( No shingles. Yet. 🙂 )

  23. BDBinc says:

    JD How about placeboax the treatment that is great for no evidence based ” new diseases” (w flu symptoms) and ( as yet non isolated and non proven to cause “covid” cough the flu in healthy people when they breathe it in) ” new deadly viruses” that everyone has now been exposed to a year later and you are going on about a rushed untested vaccine said to only “lessen symptoms”( dubious claim)as though that is sane.
    Almost every Dr I know is eating up the media mis -science without seeing any evidence or doing any reproducible research on proving the new virus exists, that its not Sars CoV 2002 or that it causes a new set of symptoms.
    What happened to” first do not harm”?

  24. Ken says:

    Gee, I read Derek’s article and felt pretty good, but now that I’ve read the comments I realize that there’s no point even using these vaccines and we’re all doomed. Ah well, such is life.

    1. Derek Lowe says:

      Gotta remember a key law of the Internet: never read the comments. It’ll probably apply even here until the pandemic recedes. . .

  25. E Ray says:

    I’m kinda interested to know what the efficacy is for all the people who will get their first shot of a 2-dose vaccine and fail to ever get the 2nd one. I wonder if there is clinical trial data for that group? I imagine this might be a large group. Or, what if they get the 2nd shot at 3 months instead of 1? Or 2 weeks?

    1. sidhivpharma says:

      don’t know but we need to take care of ourself

  26. Janis Petke says:

    Nobody can just go to a medical doctor or pharmacy and just choose which covid-19 vaccine to buy. Even medical doctors can’t do that.
    So let’s talk about other vaccines.
    We have seen some studies MMR and flu vaccines give some protection against covid.

    Flu vaccines:
    Live flu vaccine = nasal flu vaccine: FluMist Quadrivalent in USA, is probably 100% the same vaccine as Fluenz Tetra given in UK and other European countries.
    Should live vaccine given first, then the “dead” flu shot earliest 4 weeks later?

    MMR vaccines:
    The most studied or maybe the only studied MMR vaccine against covid-19 is the M-M-R®II.
    What if one got M-M-R®II on May 2020 and now gets some other MMR vaccine in December 2020? Better idea than getting the same M-M-R®II again?

  27. Marmaduke Horseman IV says:

    There have been a few in vitro studies suggesting ADE by actual antibodies from COVID-19 patients, including this from today:

    Query whether ADE is more of a rule than an exception but not frequently a problem because the ratio of neutralizing to enhancing ab is very high. There’s a lot of variety and it’s probably not that hard to find one or two that help the virus.

    The other interesting issue with suboptimal abs is the recent concept that proteins such as S are driving immunopathology by themselves, and ab may neutralize these without blocking the RBD. But of course stabilization of toxins is also possible.

  28. Aztec Family says:

    If someone is non-responsive to polio vaccine, is there a chance they will also be non-responsive to COVID vaccine. Polio vaccine given in 1964 but I was a non-responder and developed paralytic polio in 1968.

  29. jagadish says:

    let’s hope for the best

  30. Razzledazzle says:

    I live in England and am aged 81, in reasonable health. I got my first vaccination (Pfizer) on 16 December and was immediately given an appointment for the 2nd on next Wednesday, 6 January.
    Our government announced yesterday (31 December) that second doses are to be deferred to 12 weeks instead of 3 weeks. In response Pfizer has issued a statement that there are “”no data” to demonstrate that a single dose of its coronavirus vaccine will provide protection from infection after 21 days; and that although some protection appears to begin as early as 12 days after the first dose, two doses of the vaccine — separated by three weeks — is the only regimen that proved to be 95% effective in Phase 3 trials.
    I am very angry. If my appointment next Wednesday is cancelled, do I have the right to sue?

  31. Ali Reda Rabiah says:

    I took the Sinopharm Chinese vaccine, it was the only one available in my country more than a month ago, its a classical vaccine with inactive covid virus and aluminum adjuvant. Report says its around 70% effective, far from the 90-94% of the arn ones.
    Now that Astra is rolling out in my country and that Pfizer is due next month I am wondering if I should get another shot with one of those since they are different kind of vaccines with both higher efficiency.
    Hope anyone has any clue.

  32. Jonah says:

    In all likelihood getting different vaccines is not dangerous and will at least give you the protection of the best one, if not better. I’d be following the efficacy data between prized and astra against the South African variant when choosing which one to use.

  33. Zaizai says:

    Can I have two types of vaccine? for example only: 2 doses of Pfizer then after 3 months 2 doses vaccine from Sinopharm. Is that ok?

    1. Tara Sgroi says:

      I’m wondering as well for my parents who regret taking the AZ vaccine now 🙁

  34. DataWatcher says:

    The mixed messages on this, from “mainstream” media anyway, are indeed frustrating. In today’s New York Times, Paul Offit is paraphrased as having “said” that “[p]eople who take the Johnson & Johnson vaccine should be able to safely receive a Pfizer-BioNTech or Moderna vaccine later if a booster shot is needed.” Then, just four paragraphs later, Vanderbilt’s William Schaffner is quoted as saying that “it is not known yet whether it would be safe to take one vaccine now and then another later . . .[because] we haven’t studied that,.”

    Can’t blame people for being confused and anxious.

  35. Tara Sgroi says:

    My parents live in Mexico, they’re in their late 70s, last week they were fortunate to receive the Astra Zeneca vaccine. They were so happy until all the news came out about its lack of efficacy in people over 64 years old. What can they do? Can they take another vaccine? Should they not take the second dose? Will they be alright? 🙁 I can hear the sadness & frustration in their voices. Please advise.

    1. Mariner says:

      There isn’t any data indicating a lack of efficacy of the AZ vaccine in over-65s.

      In fact, the data in the pre-print published in the UK today seems to indicate it is on a par with the Pfizer vaccine, for example. Even if it proves a little less effective than the mRNA vaccines, it ought to offer very good protection.

  36. Carlos Lozano says:

    Is it safe to get vaccinated against hepatitis B once you have been shot with de Pfizer vaccine 2 weeks before. If it’s safe, may I receive the second shot without any trouble?

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