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A Wider Variety of Vaccine Platforms Report

Well, it’s definitely been a Vaccine Week around here, but it’s understandable. And we’ll finish off the week with a look at some types that we haven’t seen report yet. The news is. . .mixed.

First off is a preliminary report on the inactivated virus vaccine from Sinopharm – more specifically, their China National Biotec Group division, and even more specifically CNBG’s Beijing Institute of Biological Products. As a side note, if you find the organizational structure of these Chinese efforts somewhat confusing, come sit right over here next to me. A press release from the United Arab Emirates’ Ministry of Health and Prevention says that a trial there showed 86% efficacy and that there were no serious safety concerns. I would bet that this is a higher figure than most people expected from an inactivated-virus candidate – it’s an older technology that doesn’t always come through (but has certainly also generated some very useful vaccines in the past).

Unfortunately, that’s about all the release has to say – there are few further details. The 86% is said to be for preventing coronavirus infection, but we don’t know if this was measured by number of patients with symptoms or counting in asymptomatics via PCR testing. The release also says that the vaccine was 100% effective in preventing moderate or severe cases, which is also very good, of course. It’s a two-shot dosing regimen, and the vaccine itself is said to have no special storage requirements. So there’s a lot of promising stuff here, but there’s a lot to wonder about as well. I know that we’ve had a lot of press releases in this vaccine clinical trial business so far, but most of them have them have been a bit more informative than this. And although some of the Chinese development efforts have released and published good data sets, others have been very much lacking, and this is one of them.

For example, neither Sinopharm nor the Chinese authorities have had any comment on this announcement. And that’s odd. Indeed, the New York Times reports that one of their reporters got through to Sinopharm only to have them hang up the phone when asked for comment. So I’m not just being hard on this one because it’s from a Chinese company – this is weird by any nation’s standards. If I’m going to give Oxford and AstraZeneca grief for the way they rolled out their recent trial announcement – and I do, because they deserve some – then I’m going to give Sinopharm some for this. If they weren’t ready for a press release from the UAE government, they should say so. Hanging up the phone on people is not the way to build confidence in your organization and its skills. At any rate, the efficacy numbers from this single press release are good news. The UAE has now approved it, and shipments of it are already going to Egypt and Indonesia, among other countries. I would just feel better if I could hear the actual developers of the vaccine say something about it, and with some more numbers attached.

We also had news this morning from the GSK/Sanofi effort, but the news is not good. They have been working on a recombinant protein vaccine with the addition of GSK’s adjuvant, but the companies announced that a look at immunogenicity in Phase I volunteers showed an inadequate response in older patients. The 18-49 year old cohort apparently looked good, but when compared to convalescent plasma antibody levels, the levels in the older vaccinated patients were not. The companies plan to start up again in the clinic in February with an improved antigen formulation, but this will definitely delay their vaccine to (probably) the end of next year, and that’s assuming that the new version works as hoped.

That’s unfortunate. We need as many solid vaccines as we can get, and I don’t think anyone was really expecting something like this from the Sanofi/GSK team (they certainly weren’t). The two companies have a long track record in this area, but immunology is what it is – these results show that we can take nothing for granted. In fact, together with the lower efficacy seen in the Oxford/AZ candidate, I have to say that this is making the mRNA platforms look stronger all the time. More on this in a separate post next week. Anyway, in the same way that the Oxford/AZ data make me very curious about what we’ll see from J&J’s trial, these results make me similarly ready to see what Novavax will report with their own recombinant protein/adjuvant candidate. But they did have reasonable antigenicity numbers, at least. And in that first link in this post, the team at Science says that they believe that another inactivated-virus candidate (from Sinovac) may soon report on its trial in Brazil, so we’re going to have plenty of comparisons to think about.

Finally, word has come that an unusual vaccine candidate has had to stop development. In my earlier huge vaccine roundup posts, I mentioned the University of Queensland and their “molecular clamp” technique. Here’s more on how that is supposed to work. The idea is to use a trimeric protein that’s from HIV, a part of its gp41 glycoprotein, as a molecular platform to display the antigen proteins from whatever other virus you choose. The Queensland candidate (which was being developed with biotech company CSL) displayed the coronavirus spike protein this way, in what was believed to be exclusively its pre-fusion conformation. The idea looked like it would be readily adaptable to many viral proteins, and easier to realize than some of the other scaffolding ideas like this that have also been looked at.

Unfortunately, the use of this protein fragment also caused antibodies to be raised to it as well as to the Spike protein part, and that led to false-positive HIV tests in the trial participants. It’s important to note that these are indeed false positives – the vaccines used only a piece of one HIV protein and this has nothing to do with an actual HIV infection, of course. But wide use of such a vaccine would basically blow up the ability to do routine HIV blood screening, and that’s not good. Especially when there are other vaccine candidates out there with no such liability. Work on this one has ceased, and this would appear to throw into doubt any further plans to use the gp41 platform for future vaccines.

Update: there’s some more news. AstraZeneca today says they’re looking at combinations of the Oxford/AZ adenovirus vector vaccine with others. That includes the mRNA candidates and (interestingly) the Russian “Sputnik” vaccine from Gamaleya. Details on that latter one have been very much lacking. I’ve written here about the possibility of people getting more than one type of vaccine, so I’ll be glad to see some controlled data on the mix-and-match approach in general, while keeping in mind that (immunology!) every one of these situations could be different, all the way down to what order the vaccines are given in. To me, this also suggests that AstraZeneca is hedging against the possibility that their candidate may simply not be able to compete as a standalone agent in the eventual coronavirus vaccine landscape. . .

100 comments on “A Wider Variety of Vaccine Platforms Report”

  1. sPh says:

    Should a responsible government encourage GSK/Sanifi to go in the other direction with trials in the 9-17 range with a goal of increasing the total availability of all vaccines? New HPV vaccines are generally labeled 9-26 at release so an upper age limit is not unprecedented l.

    1. Marko says:

      This guy is saying GSK/Sanofi will be seeking approval based on non-inferiority , which strikes me as a significant phase change in the vaccine space , if true :

      https://twitter.com/biosbenk/status/1337443130858147842

      1. Marko says:

        Looks like it is true :

        “…Sanofi ….is proposing to the Food and Drug Administration that its Phase 2b trial compare its vaccine to one that is already authorized, not a placebo.

        “To continue to provide confidence that we’re going to have a vaccine that meets the expected standard of care, we propose the comparison with an authorized Covid-19 vaccine instead of placebo control,” Ng said..

        https://www.statnews.com/2020/12/11/sanofi-suffers-major-setback-in-development-of-a-covid-19-vaccine/

        1. Dick King says:

          To gain statistical significance, you need about a hundred diagnosed infections.

          With mRNA recipient groups of 20,000 getting only about ten infections in the trials we’ve seen so far, that group will have to be quintupled, so the entire trial would need to have 200,000 participants or more.

          -dk

          1. Chris Phillips says:

            Whether you’re going to get statistical significance obviously also depends on other factors than the total number of infections across the vaccine and placebo arms – namely, the efficacy of the vaccine (which will reduce the total number of infections, but may not reduce the statistical uncertainty) and the relative sizes of the vaccine and placebo arms (which may do the same).

            You can get adequate statistical significance with a much smaller total number of infections, provided the vaccine is highly effective and/or the placebo arm is relatively small.

            Really, you just have to calculate the statistical significance, not look at the overall numbers and try to judge whether they’re large enough.

      2. HA2 says:

        That seems to make a lot of sense. Now that we’ve got real vaccine candidates proven to work, compare to them instead of placebo – it neatly gets around the question of “what if people in the placebo group get vaccinated anyway.”

    2. Clyde Schechter says:

      The reason HPV vaccines are labeled only for use under age 26 is that, in the absence of immunization, nearly everybody already has been infected by HPV by age 26. At that point there is no benefit to immunization: you either have an established chronic HPV infection, or you have cleared the virus and have natural immunity. Either way, the ship has sailed.

  2. Ezra Abrams says:

    Derek
    I am sure that back in March/June, I read about something like 200 (! !) vaccines in development
    Of course, “in development” is biotech’s favorite weasel, but, Surely there are some more out there then the ones you mentioned ?

    Or did the massive amount of money spent on OWS scare everyone else off ?

    1. Tom H says:

      Wikipedia says a total of 209 vaccine candidates. Of those, only 13 have progressed to human trials.

      Apart from BioNTech-Pfizer, Moderna and AstraZeneca-Oxford, we have J&J (viral vector), Curevac(mRNA) and Novavax (protein nanoparticle) — plus Sputnik and at least five different Chinese ones. I think J&J is the only one that could be expected to be submitted for approval in the near term.

      1. Chris Phillips says:

        I think you mean “submitted for approval in the USA”?

        I wish people could be a bit less parochial sometimes, and bear in mind this is a worldwide crisis, and a large proportion of the world’s population isn’t as rich as the people in the industrialised West.

  3. pbj says:

    It’s not scientific at all, but I’m almost relieved at some bad news. It would have felt very weird if everything we threw at the board stuck.

  4. Jd laberge says:

    Any news on the medicago phase 2-3 trials yet ?
    Thanks

  5. Ammar Hasan says:

    The messy organisational structural for the Sinopharm trial is probably the cause of the poor communication. I think the UAE trial was ran with some degree of independence by another company, so maybe Sinopharm is reviewing data before commenting?

  6. SteveM says:

    The U.S. MSM is gushing over the Pfizer product like it’s the dominant winner.

    Given that other vaccine candidates have reported similar 90%+ efficacy, I would think the Pfizer vaccine would actually be a secondary candidate given its logistics requirement for ultra-cold storage and handling.

    Re: “That includes the mRNA candidates and (interestingly) the Russian “Sputnik” vaccine from Gamaleya. Details on that latter one have been very much lacking.”

    Second interim analysis of clinical trial data showed a 91.4% efficacy for the Sputnik V vaccine on day 28 after the first dose; vaccine efficacy is over 95% 42 days after the first dose:

    https://sputnikvaccine.com/newsroom/pressreleases/second-interim-analysis-of-clinical-trial-data-showed-a-91-4-efficacy-for-the-sputnik-v-vaccine-on-d/

    Is the Gamaleya self-reporting more suspect than its competitors? That’s a real, not a rhetorical question.

    Also note that MSM Russia Hate is still throwing shade on Sputnik V regardless of the reported positive results and the quality of the underlying science. It’s all a “Putin plot”.

    1. Matthew says:

      Well, it’s currently based on reporting of only 39 cases, while Pfizer, Moderna and AstraZeneca are all based on a lot more than that. So the statistical significance of their data is definitely lacking by comparison.

      It’s not to say that it won’t be proven to be effective, it’s just to say that 120+ pages of data after 170 cases is a lot more reliable than a press release after 39. For now.

      1. Marko says:

        The 3:1 split in vaccine to placebo reduces the overall number of events. In a 1:1 trial , there would have been ~100 events. The use of unbalanced arms in this way makes sense if you’re certain that there’s sufficient disease incidence in your trial population to give you the numbers you need in a reasonable time.

        1. Ian Malone says:

          It’s possible to come up with some estimates based on the numbers in that table, you get about 81%-96% confidence intervals for efficacy around their 91% point estimate (using 95% confidence intervals). I note their centre director on that page says “91-92%”, which might give the impression of an uncertainty range but actually can only mean the point estimate is between the two, the actual value could easily be different.

          This is not too far off what we had for the early Pfizer press release, quite a different situation to the very early analysis at 20 infections from Sputnik V. Not being a trials statistician I don’t know what additional worries there might be about the unbalanced arm design, it probably makes things a bit more difficult if you do have adverse events (because they’ll be rarer and more variable in the control arm), 4,500 is also maybe getting a bit low in terms of randomisation. Now we can see more data for Pfizer and Astrazeneca it’s possible to be much more certain for them about how well things are balanced and that efficacy still applies in subgroups (maybe another issue for an unbalanced arm design, your subgroups in controls are going to be quite small).

          It’s on track to looking like it works quite well, what we don’t know from the outside is what the detailed data show. (And need some more cases to nail down that uncertainty if you want to say it’s as good as Pfizer or Moderna.)

          1. Ilya says:

            The interim analysis in the Sputnik protocol is not prespecified, they just unblinded the data a day after Pfizer’s announcement. Furthermore, there is no accurate description of who is considered having COVID-19. Illness visit is not required, even PCR-confirmation is recommended but not required. There is no strict algorithm to determine symptoms sufficient for a participant to be deemed positive, unlike Pfizer and Moderna’s protocols.

            All this creates huge biases and ground for data manipulation by PIs, given that the side effects (limb pain, fever) unblind those who are in a vaccine group immediately.

            Also, GxPs are very sparsely implemented in Russia, you may have heard of Turkey rejecting Sputnik dossier, as it was non GLP-compliant.

          2. Marko says:

            “The interim analysis in the Sputnik protocol is not prespecified, they just unblinded the data a day after Pfizer’s announcement. ”

            Source ? No ? I didn’t think so.

          3. Chris Phillips says:

            In any case, if the data were blinded, how could unblinding at any date they chose introduce bias? That’s the point of blinding!

    2. sPh says:

      No one actually working in cold chain logistics in the US or Canada has expressed any concern about the Pfizer -70 requirement. Wal-Mart announced today they have been working on equipment and procedures for months; that’s 3200 pharmacies. Walgreens similarly sent an email today saying they will be ready when they receive vaccine – another 3000 delivery points. And our regional hospital is looking at shuttling in medical personnel from outstate clinics to get their shots.

    3. sgcox says:

      It is also funny how Russian news sites praise new AZ/Sputnik trial. It was lambasted in summer as “monkey vaccine” with Boris Johnson shown as baboon. Well, fully agree on the later point.

    4. PV=nRT says:

      Part of this disdain among the US MSM for vaccines from other nations may be borne out of the fact that certain governments have a hand in data and results. In the US & UK, scientists are independent (or they were until just this year).

  7. Tony Warren says:

    Nobel Laurette Dr. Michael Houghton at the University of Alberta has a vaccine that his virology group is developing and I believe is going into phase II trials.

    Worth checking out.

  8. myst_05 says:

    Gotta love the logic of bioethicists…

    >> Hey guys, can we maybe run a vaccine challenge trial to help accelerate research? We’ve got 30k volunteers signed up already

    Aw jeez, that would be horrible! Humans are unable to consent to taking a deadly risk! (though lets ignore doctors volunteering to work despite PPE shortages or soldiers volunteering to fight in remote countries) We might harm a few hundred people with this challenge trial so its best if we just run a Phase 3 trial and wait for months and months to get the results. Who cares if lives could be saved by accelerating the research?

    >> Hey guys, we’ve got this vaccine candidate that’s only effective on young people. Can we just launch a Phase 3 trial for young people while we run a separate Phase 1/2 trial for older people?

    Aw jeez, that would be bad! Old people are people too and we might hurt someone’s feelings if we declare that there’s a vaccine that’s only available for young folks. Lets just delay it by many months instead to the point where it becomes irrelevant, even if it could’ve saved tens of thousands of people in the meantime.

    >> Folks, I’ve got this Oxford vaccine that’s 62% effective and has no major side effects. Can we start using it?

    Aw jeez, absolutely not! Some people might get offended because they could’ve received the 90% effective vaccine instead, even if that 90% vaccine is in short supply and wouldn’t actually be available to them for many months to come. Rather than offending people, we should just let them die from COVID – that way we’re not to blame for anything. So lock that vaccine up until you run many more trials and ignore the fact that this causes tens of thousands of extra deaths. Bio ethics above all!

      1. metaphysician says:

        Ugh, that comment section.

        As an aside, one of the costs and challenges I have yet to see acknowledged by the pro challenge trial brigade: hospital beds. If you do a challenge trial with 1000 volunteers, you know how many hospital beds in an isolation ward you need? 1000. With all necessary staff and intensive care materials for all of them. This is stuff you aren’t going to find growing on trees during a damned pandemic. But then, the advocates of human sacrifice do like to glide over the actual ethics of the situation. I mean, so many people are getting it anyway, why not deliberately kill a few more people?

        1. Sir_toadswallow says:

          Since trials don’t usually need to have thousands in the same location at the same time, hospital beds could be spread between places that have low hospital usage.

          Of course, that assumes the majority need hospitalization. If the challenge trial uses young, healthy volunteers, the need for actual hospital treatment is limited. The primary concerns would be monitoring and isolation. Early on hotels, college dorms, and cruise ships all had many excess beds, and the military has the ability to make field hospitals. The small fraction who needed an actual hospital would be transported there.

          And regarding undesirable comments- personally, I’d considered the isolation issue months ago, and it took less time to think of an answer than to write it here. I do not think it was a difficult problem to solve. To me, it seems like you preferred to think HCT advocates were blind to the harm inflicted on volunteers, rather than try for a couple minutes to think how we’d solve the problem.

    1. Tom Rearden says:

      It makes more sense if you accept that the medical field is dominated by people who excel at test taking, not necessarily thinking. Given the absolute mess they have made of the testing regime and a school closures, we should expect their vaccine logic to be equally asinine. Only a person programmed to answer closed ended questions with a high degree of accuracy could possibly think PCR tests are useful for slowing the spread.

    2. Chris H says:

      I loved your comment.

      The reality is that any of the vaccine candidates are statistically much better for most groups than no vaccines. If the FDA were to actually follow their own standard, they would have approved all candidates for high risk after phase I, and for others after phase II.

      I have started calling it as “lifting the ban” instead of “approval” as I think that more accurately reflects the situation.

      We had not 1 but about a dozen vaccines proven at least “much more safe than covid” and “probably effective” in July, but we lacked the mechanism to even allow doctors to take it themselves.

      The first 3 months of the pandemic might be considered caused by the disease, the rest is due to the vaccine ban.

  9. Marko says:

    “Key insight from @CDCDirector Redfield — this year in USA we “see record lows in #flu” because of all the contagion control measures taken for #COVID19 — yet COVID is soaring. This means COVID is FAR more contagious than flu.”

    https://twitter.com/Laurie_Garrett/status/1337451154616291333

    Same conclusion previously reached based on flu surveillance in the southern hemisphere. See comments in the tweet thread that show the Covid denialists refuse to be denied by mere data.

    1. sort_of_knowledgeable says:

      A couple of confounding factors.

      New strains tend to originate in Asia and travel west to the US. Travel is way down so lower spread of more contagious flu strains through that mechanism.

      Higher numbers of people taking flu vaccines this year because of fears of double flu, covid-19.

      1. Marko says:

        ” A couple of confounding factors….New strains tend to originate in Asia and travel west to the US. Travel is way down so lower spread of more contagious flu strains through that mechanism.”

        That’s a supporting factor, not a “confounding” one. Reduced travel is one of the NPIs that have been adopted , in the US, Asia, and the rest of the world, to help reduce spread of Covid.

        Increased uptake of the flu vaccine is probably having some effect , however , depending on its relative efficacy vs. circulating flu strains.

        1. Not-an-epidemiologist says:

          It’s a supporting factor in terms of saying that infectious preventative mechanisms work; but a confounding one in terms of saying that covid-19 is more infectious than flu. If you want to say that, just point to the published epi data — no need to resort to logical fallacies.

          Another reason why flu case numbers are so depressed this year is that flu isn’t infectious until symptomatic, and people with flu-like symptoms are expected to isolate (at least in my country — unsure what the situation is in the US?) The infectious-whilst-asymptomatic characteristic of covid-19 is what has made it so difficult to control when compared to earlier potential pandemic candidates.

          1. theasdgamer says:

            I’ve noticed that whenever cases start dropping, the county health department starts advertising their free testing service. People respond with the clowns symbols.

          2. Dieles Stolk says:

            Another supporting factor, next to all the other measures, might be viral interference. It seems that during the 2009 influenza pandemic, one of the reasons it didn´t grow into a full-scale pandemic, might have been viral interference form rhinoviruses.
            https://www.thelancet.com/journals/lanmic/article/PIIS2666-5247(20)30114-2/fulltext
            I haven´t found much research on Sars-Cov-2 and Influenza, but it´s a possibility that Sars-Cov-2 is interfering with Influenza. Or that, again, rhinoviruses are doing this because they get more room to play (less Influenza) because of the measures.
            There are some studies about coinfection that may point in this direction.
            Interactions between SARS-CoV-2 and Influenza and the impact of coinfection on disease
            severity: https://www.medrxiv.org/content/10.1101/2020.09.18.20189647v1.full.pdf
            And Coinfection in SARS‐CoV‐2 infected patients: Where are influenza virus and rhinovirus/enterovirus?
            https://onlinelibrary.wiley.com/doi/10.1002/jmv.25953

        2. sort_of_knowledgeable says:

          At this point travels from Asia would be much more likely to have the flu than SARS-COV-2. The claim was made that the disease prevention measures in the US reduced the flu because the flu rates are down this flue season. However if there were fewer cases brought over from Asia at the start of the season then would be less cases recorded during the season even if the control measures remained the same.

    2. theasdgamer says:

      Typical puerile thinking from you.

      Flu PCR Ct is 27-28.

      Covid PCR Ct is 37-45.

      Both are fairly ubiquitous.

      Wonder why Covid shows up more?

  10. exGlaxoid says:

    The data also seems to indicate that the Pfizer vaccine could be given in one dose for now, and we could delay the booster for 3 months, thus vaccinating double the number of people up front. There is no reason to think that is not the case, but I doubt that anyone will allow it. I have heard that the first shot is up to 90% effective within ~14 days, so I don;t see how that is much different from 94%, and I would rather see the most people possible prevented from getting sick or dying in the next 3 months. I also don’t see why the FDA needs 3 days to approve the vaccine once the committee gave it a good review (not that there was much doubt). It’s not like 3000 people are dying each day and hospitals are critically short of staff. Plus the 90% efficacy appears to be within ~14 days of first shot, so much faster than saying it takes 4 weeks to work, as the media keeps saying.

    1. DataWatcher says:

      Sounds encouraging — my understanding was that the first shot alone was about 50% efficacious, which sounded a bit problematic to me. If it really is around 90%, I’m right in there with the “one shot for now” advocates. I wonder if Moderna will come up with similar one-shot results?

    2. Craken says:

      Does the data show the results in people who received the first shot, then no further shots for 3 months? I thought that virtually all study participants received a booster about 3 weeks later.

      1. Dieles Stolk says:

        They get the second shot 21 days after the first one. And you really need to do it after 21 days, can´t delay it for three months (at least, there is no data to gauge what kind of effect that would have).
        Check the UK information for Healthcare professionals on the bottom of this page:
        https://coronavirus-yellowcard.mhra.gov.uk/productinformation

  11. Anthony Serritella, MD says:

    Does the data already presented in the NEJM for NVAX candidate (Keech, et al) showing IgG titres, neutralizing antibody titres, and the T-cell responses in 16 patients showing the strong bias towards Th1 responses (reflected by IFN-gamma, IL-2, and TNF-alpha production on spike protein stimulation) enough to allay fears that may be raised by the failure of the Sanofi/GSK vaccine or could NVAX still suffer the same fate?

    1. Valdis Andersons says:

      Sanofi/GSK noted low nAB responses in older participants, hence the restart. Even in the younger participants the levels were just about matching the convalescent panel. I think the rather low efficacy numbers of AZ/Oxford made them reconsider as their phase 1/2 data looked similar and viral vectored vaccines induce CD8 responses as well, potentially aiding efficacy numbers. Protein subunit vaccines don’t induce CD8 responses.

      Novavax had like 10x higher nAB levels than their CP panel and their NHP study showed complete protection outright in all animals. They should be fine I think. Even Pfizer/BNT didn’t have that stellar NHP results.

  12. theasdgamer says:

    Simply beleeeeeeeve in the PCR.

    What a herd of sheep!

    1. sgcox says:

      Yes, I do.
      PCR is done almost every working day in my lab as well as in thousands of labs across the world. Reliably and accurately.
      Not just for viral load detection but basically in all modern molecular biology work.
      It simply works.

      1. theasdgamer says:

        So you set the cycle threshold to 42, amirite?

        1. Arpic says:

          I’ve no doubt @sgcox and the others who actually use PCR every day know a sight more about how to maximise sensitivity and specificity than all the University of Youtube graduates who seem to have unlimited time on their hands to post Covid nonsense. Naming no names of course…

      2. theasdgamer says:

        Did you read this review paper of PCR/viral culture studies? (click on PDF)

        https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa1764/6018217

        “Conclusion

        Complete live viruses are necessary for transmission, not the fragments identified by PCR. Prospective routine testing of reference and culture specimens and their relationship to symptoms, signs and patient co-factors should be used to define the reliability of PCR for assessing infectious potential. Those with high cycle threshold are unlikely to have infectious potential.”

        Exec summary: PCR reliability is unknown. (But of course PCR will be used for vaxx studies just because.)

  13. Barry says:

    Seems the fix for the GSK/Sanofi vaccine MIGHT be as simple as giving more of the same adjuvant to subjects >50yo.

  14. Elliott says:

    There are indeed plenty more vaccines in development.
    The media has been concentrating only on the hares, but some of the tortoises deserve a look. Merck for instance, has two vaccines in the works. They are using established systems and are aiming for single dose, possibly oral administration, without the cold-chain requirements posed by the new mRNA-based vaccines. Last I heard, they were still in Phase I, and it will be interesting to see if development will be continued in the face of such good results from Pfizer and Moderna. It will depend upon efficacy–the bar for that is now higher.

    Then there’s my other favorite–Inovio. Remember them? They’re the ones that invented a vaccine in three hours. It wasn’t until you got to the fine print that you found out that testing would still take over a year. I think that they ran into some issues and are currently in PhII.

  15. Candido says:

    Regarding the Sinovac vaccine which it is being tested here in Brazil, in a partnership with the Butantan Institute in São Paulo: we heard sometime ago that 61 cases of Covid-19 were detected in the trial and that they were going to have preliminary look at the data about efficacy. Well, it has been more than two weeks and now they changed their mind and they will release it only on December 15th. Meanwhile, politics about the success of this it are being exhaustively explored by the State Governor, a political opponent of Brazilian lunatic President, to the point that the vaccine is already seen as hugely effective against the disease. We are all hopeful but seriously, how long it takes to analyse the efficacy of 61 cases???

  16. Marko says:

    Amazing , on any given day, take the 7-day average of daily cases, multiply by 1.7%, and you get the 7-day average of deaths 22 days from now. This relationship has been remarkably stable since August, with only a recent slight underprediction of deaths associated with the leadup to Thanksgiving :

    https://twitter.com/trvrb/status/1337570836878749696

    I suspect that tests and cases were over-represented in the week or two before Thanksgiving, as people sought tests prior to their holiday travel and gatherings with family, causing the recent apparent underprediction of deaths.If anything, as we follow this relationship , I think we may soon begin to see a somewhat higher apparent lagged CFR, as hospitals and ICUs become overwhelmed and quality of care suffers.

    1. Marko says:

      Correction : “underprediction of deaths” in both cases above should be “overprediction of deaths”.

    2. theasdgamer says:

      Got any links for a working false positive rate for covid PCR tests? Didn’t think so.

      1. sgcox says:

        Several countries implemented mass testing with strict quarantine rules to suppress epidemic.
        Countries like Australia, New Zeeland, Hong Kong and Taiwan. All with advanced and transparent health systems. I would actually trust them more than US or UK statistics.
        The ratio of positives to total there are between 0.1% to 0.5% (calculated from worldometer website)
        Even if we assume the null hypothesis and covid simply does not exist, which is patently bullshit, false positives of PCR would be around 0.2%. In the real life of course it is much, much smaller as many people in these countries get seek, hospitalized and even died and null hypotheses is false.
        I am sure there will be some heated replies which is fine of course, but I will stop commenting here and wait for a new exiting post from Derek on Monday. Take care.

        1. theasdgamer says:

          Cool story, bro.

          Working false positives depend on the prevalence of minimal levels of viral RNA in the population as well as contamination issues. When the prevalence is high, false positives will be high and RNA prevalence will outweigh contamination issues. The more that real covid is present in the population, the more that minimal levels of viral RNA will also be present in the population because more people will be exposed than infected with a viral load heavy enough to generate an active immune response. Passive immune responses will deal with light viral loads and leave small amounts of viral RNA in the nose.

          1. Arpic says:

            These must be truly amazing “minimal levels of viral RNA”. Being able to increase exponentially without an infectious virus exponentially increasing too.

  17. Mark says:

    Can anyone offer some advice, I’m a British expat living in the UAE with family. I’m torn whether or not to get the Sinopharm vaccine based on the limited “data” released so far. I doubt I’ll be back in the UK anytime soon, and even if I was I would be very low down the priority list (mid thirties, not obese etc). So I’m leaning towards getting the Sinopharm one here. Am I mad?

    1. johnnyboy says:

      It’s an inactivated vaccine, so in theory, unless you have a tendency to have allergic reactions, it should be pretty safe. I would say the main safety risk would be around possible manufacturing issues, leading to the vaccine prep containing impurities (or not the amount of virus that’s it’s supposed to have). Manufacturing in China is not as strictly regulated as in the west, and in the Covid rush it’s probably even less so. In the end it’s all about risk-benefit management. So you balance the risk of having vaccine-related problems against your own particular risk of getting Covid and what the consequences would be, according to what your current status is (are you socially distancing adequately, do you have risk factors for severe disease, what are the infection levels around you, what would be the level of health care you would have access to if you got sick, etc…). If I were you, if there is a relatively high chance of you contracting Covid and if you have risk factors for severe disease, then I would go for it (and then repeat vaccination with another vaccine when that becomes available, to mitigate the risk that the sinopharm has lower efficacy than reported). If there is little risk of you getting Covid at the moment, and if you are young and healthy, I would wait until you get access to the Pfizer/BioNtech or the Moderna.

      1. Mark says:

        Thanks for the detailed reply, johnnyboy. A lot to consider for sure, there is definitely a very high standard of healthcare out here and the rate of people dying from covid is very low (well under 0.5%). So I might just wait for a western vaccine later on.

  18. Derek Lumsden says:

    I’m afraid of needles, is there anyway I can take the vaccine in rectal table form?

  19. Steve Scott says:

    The AstraZeneca/Sputnik V partnership is apparently based on the idea that you would develop some immunity to the Adenovirus in the first shot, so the booster shot wouldn’t be as effective. If you have different Adenovirus platforms in the two shots, however, that potential problem no longer exists.
    Sputnik V uses the AD26 virus, that large numbers of people have been previously exposed to throughout the world (especially sub-Saharan Africa where an estimated 50-90% of the population had pre-existing antibodies to AD26. 10-20% in Europe and the U.S. Johnson & Johnson’s vaccine uses AD26 but is based on only one shot. J&J previously tried out HIV and Ebola vaccines on 80,000 people in Africa, using AD26 and said the levels measured in those vaccines was not high enough to trigger an immune response to the AD26. However, there was also a booster shot of a different vaccine. Anyway, this background might help to shed more light on why AstraZeneca and Russia want to cooperate. If you believe the test results so far, however, both of them seem to be highly effective on their own- if the “half dose” followed by “full dose” for AstraZeneca really does the trick.

    1. SteveM says:

      Re: “Sputnik V uses the AD26 virus”

      Sputnik V is actually a 2 vector vaccine, AD5/AD26:

      https://sputnikvaccine.com/about-vaccine/

      I’m a layman with this, but guessing that AZ wants the Sputnik AD26 component in order to reach an effectiveness threshold while for Gamaleya the collaboration incentive is strictly economic.

      1. sgcox says:

        Makes sense to mix AZ with J&J which is Ad26.
        But I guess it is easier to negotiate with Putin than patent lawyers.

    2. Derek Lowe says:

      I think the seroprevalence numbers you’re quoting are for Ad5, not Ad26?

      1. Steve Scott says:

        “J&J’s Janssen is using a rarer adenovirus subtype, Ad26, in its COVID-19 vaccine, reporting in July that it protects macaques against SARS-CoV-2 and in September that it protects against severe clinical disease in hamsters. Ad26 neutralizing antibodies are uncommon in Europe and the US, with perhaps 10–20 percent of people harboring antibodies. They are more common elsewhere. “In sub-Saharan Africa, the rates are ranging from eighty to ninety percent,” says Ertl.”

        https://www.the-scientist.com/news-opinion/vector-based-vaccines-come-to-the-fore-in-the-covid-19-pandemic-67915

    3. WST says:

      AZ + Sputnik V, as if AZ didn’t have enough of own problems, sound more like multiplying difficulties. One thing common to them is the technology, a DNA type of vaccine. Maybe Russians hope for help in manufacturing ?
      Even Putin admits productions problems

      https://thebell.io/en/production-problems-hamper-russian-vaccine-roll-out/

    4. Michele P. says:

      Gamaleya reports that their vaccine works even when the recipient has long-term immunity to one of the two vectors.
      If this is true, can we imagine that the immune system has a mechanism for killing two birds with one stone by targeting the common link between the two vectors ?
      Still conditional, but could it mean that the immune response is then more specific than homologous vaccines, thus safer?

      1. Michele P. says:

        Or is it simply due to the fact that the first shot wakes up the immunity, which blocks the second one if it’s the same vector ?

  20. Marko says:

    Another Covid-19 “storm” , of autoantibodies :

    https://twitter.com/VirusesImmunity/status/1337574470878449665

    Immune dysregulation is a bitch….

  21. Michele P. says:

    I’m sorry, I wasn’t very clear above, so I’ll ask my question again.

    It seems to me that heterologous vaccines mimic the natural situation of encountering two different strains of the same virus, close in time and concomitant in terms of immune response.
    Faced with this situation, the best strategy is to target proteins common to both strains, as this increases the yield by 50% (100% compared to antibodies specific to one of the two strains).
    I would be very surprised if the immune system did not discover this strategy, resentful and astute as it is.
    The other advantage is that this immune response is very specific by definition, and this could be good news for autoimmunity risks, wouldn’t it ?

    1. Michele P. says:

      So nobody has an opinion about heterologous vector vaccines preventing heterologous immune response ?

  22. Bill says:

    Assuming we can trust what CDC tells us:
    Current infection rate > 200,000 per day
    Actual infection rate = 8X apparent rate. = > 1.6 million per day.

    So we’re getting infections faster than the vaccine is even planned to be distributed. Doesn’t this pull herd immunity achievement way closer than they’re predicting? I make it to be about two months out, not even counting any vaccinations.

    100 million now + 1.6 million per day x 60 days = 195 million in two months.

    1. Marko says:

      “Assuming we can trust what CDC tells us:
      Current infection rate > 200,000 per day
      Actual infection rate = 8X apparent rate. = > 1.6 million per day.”

      That’s not what the CDC is telling us. Total cases to date may have been underestimated by a factor of 8 since the outbreak began , but new cases are not underestimated by the same factor currently. Testing was very slow to ramp up in the first wave , and we missed many more cases than we miss today.

      1. Marko says:

        Additionally , the only way we’re going to have 200k infections per day for the next two months is if our public health management is criminally negligent. I don’t rule out that possibility , but 200k cases per day will translate into 3-4000 deaths per day , depending on how well the health care system holds up. That’s more than a 9/11 event level of deaths every day . I suggest we try to do better than that.

  23. Bill says:

    Not saying that’s not reasonable, but any data to support it? How does one know unreported cases are diminishing? If at all.

    1. Marko says:

      I’m not doing your homework. You’re the one who made up your own data , then misquoted the CDC without a reference. The burden is on you to support your contention with some proof.

  24. Bill says:

    Gotcha. That would be a no…no data.

    1. Marko says:

      Not that you’ll understand it , but anyway :

      https://coronavirus.jhu.edu/testing/individual-states/usa

  25. Marko says:

    “On FTN, @ScottGottliebMD explains where the COVID carnage is: “There’s 50,000 new infections in nursing homes every week right now, probably more than that. And we know 20% of people in the nursing homes who are infected will succumb to the infection.” ”

    https://twitter.com/saletan/status/1338262128453627906

    ” “Head of @HMHNewJersey & @ScottGottliebMD later clarified to @margbrennan that @CDCgov is still telling @CVSHealth not to begin #COVID vaccinations in nursing homes before Dec. 21. Why? Because the government didn’t get consent in advance. Gottlieb calls it a “very costly delay” ”

    https://twitter.com/shaniben_ezra/status/1338160464077991938

    The cull continues. They call them “useless eaters”. Expendable. Soon we’ll be at 20k deaths per week , and half of them will be nursing home residents. We know how to do infection control in such settings. Only a country led by evil psychopaths would have allowed this carnage to continue for so long.

      1. Marko says:

        Indeed. That makes two evil psychopaths in the Emanuel family , at least , perhaps suggesting a hereditary component.

        As Biden himself said : ” Nothing will fundamentally change.”

        “Happy New Year” my ass……

      2. TallDave says:

        ironically this attitude seems to be becoming more prevalent just as we’re seeing the first faint rays of the dawn of the sort of comprehensive molecular–level understanding of aging that could significantly advance gerontology

        a bit like watching people throw their masks away and attend parties even as vaccinations are in trials

  26. Marko says:

    I must admit that I was a little surprised by this result from the Oxford/AstraZeneca trial :

    “…A small proportion of participants were seropositive at baseline (138 [1·3%] of 10 673 in the UK and 235 [2·3%] of 10 002 in Brazil). Three participants seropositive at baseline had subsequent NAAT-positive swabs. One participant had an asymptomatic infection 3 weeks after a first dose of ChAdOx1 nCoV-19. Two other participants in the control group had symptomatic infections 8 weeks and 21 weeks after their baseline sample was taken.”

    https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32661-1/fulltext#%20

    Although the numbers are too small to make any sweeping conclusions , 3 PCR positives out of only 138 seropositive patients is surprising to me. That’s in a similar incidence range as the seronegative placebo control group. If this is at all representative , it may mean that reinfections are more common than seems apparent , and are simply not being detected because they’re either asymptomatic or mildly symptomatic. This is not necessarily so bad if it turns out that severe disease is rare among those reinfected, but it does put a crimp in the idea of eliminating CoV-2 entirely after everyone is infected once or vaccinated. It would be nice to figure out whether most reinfections are due to waning immunity as opposed to being due to circulating immune escape mutants.

    1. Marko says:

      Oops , my mistake , that should be 3 positives out of 373 (138+235). That would put the incidence closer to that of the vaccinated group , rather than the control group , so maybe it’s not so unexpected after all.

      1. Marko says:

        On the other hand, again, maybe there is an unexpected high rate of reinfection :

        “…In the Pfizer trial there were 9 reinfections among 670 participants (1.3%) who received placebo which was the same rate as those without prior infection (259 of 19,818 participants, 1.3%)”

        https://twitter.com/EricTopol/status/1339998898476105728

        Hard to believe. If this is anywhere near the truth, why have there been so few “confirmed” reinfections? They should be everywhere. Of course, if you don’t sequence, you can’t call anything a confirmed reinfection, and in the US, we’ve done precious little sequencing.

        1. Marko says:

          I suppose that one explanation is that cases are detected in vaccine trials much more efficiently that among the general public. If most reinfections are asymptomatic or show only mild symptoms, you’d expect to detect at least those with mild symptoms in a trial, but probably miss many of them in the overall population.

          Still, I’m not sure I buy that those numbers reflect a situation where the previously-infected are just as susceptible as the never-infected. It runs counter to too much other data showing that previous infection is substantially protective against subsequent infection, for months at least.

    2. TallDave says:

      have heard some claims that COVID may just quietly circulate forever, but doesn’t seem plausible given the case trends we’ve seen (i.e. in some locales it appears to have been completely eliminated several times even before vaccinations)

      given that the most likely animal reservoir was a bat population in an abandoned Mojiang mine, suspect that even without vaccinations, natural immunity would have finished it off after a few seasonal spikes

      until it leaks again

      much like swine flu

      https://www.independent.co.uk/news/science/did-leak-from-a-laboratory-cause-swine-flu-pandemic-1724448.html

      1. DataWatcher says:

        We still have the minks, though, and I don’t think other animal vectors have been ruled out.

        1. TallDave says:

          not impossible, but much less chance any of the intermediate species becomes a permanent reservoir long after it’s wiped out in humans

          the Mojiang bats presumably already had it and may still, but they don’t have nearly as much contact w/humans as (say) fruits bats along the Ebola river

          https://www.bbc.com/news/health-44070470

  27. Earl says:

    Is this reliable?

    https://www.statnews.com/2020/12/11/sanofi-suffers-major-setback-in-development-of-a-covid-19-vaccine/

    Sounds like Sanofi had the same problem as AstraZeneca / Oxford with their low dosing.

  28. Andrew says:

    I think you confuse Sinovac with Sinopharm in the part where you mentioned Sinopharm vaccines are being shipped to Indonesia. Doses of Sinovac vaccine have arrived in Indonesia, not Sinopharm.

  29. Crni says:

    Oxford/AstraZeneca: €1.78
    Johnson & Johnson, $8.50
    Sanofi/GSK: €7.56
    BioNTech/Pfizer: €12
    CureVac: €10
    Moderna: $18

    A wide range of vaccine price differences. Link in my handle. How come the Oxford/AZ is sooo much cheaper? Because it is not as effective?

    1. FrankN says:

      These prices are payable by the member states. You need to add the EU’s financial contribution, which is unknown and may vary by manufacturer. AZ, e.g., is cheap because they have received a non-refundable EU advance payment of more than 300 m€.

    2. sgcox says:

      As I understand, Oxford insisted in a deal with AZ that during the epidemics vaccine will be distributed for no profit. At least what I read in press several times.

  30. TallDave says:

    if no one has mentioned it already, at least one peptide vaccine is entering Phase 2/3 trials

    https://covaxx.reportablenews.com/pr/covaxx-to-deliver-2-8-billion-in-vaccine-advance-purchase-commitments-110-million-doses-to-emerging-countries

    they’re a bit late to the party but in the long run, peptides may emerge as the most effective vaccination solution

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