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The Curious Case of CureVac

The German newspaper Welt am Sonntag has reported that the Trump administration has been making overtures to the German vaccine company Curevac. Here’s the part that’s really making headlines (my translation below):

Der US-Präsident bietet der deutschen Firma angeblich einen hohen Betrag, um sich ihre Arbeit zu sichern. Von einer Milliarde Dollar ist in Berlin die Rede. Besonders problematisch ist: Trump tue alles, um einen Impfstoff für die Vereinigten Staaten zu bekommen. „Aber eben nur für die USA“, heißt es in der Bundesregierung.

The US President is allegedly offering the German firm a large amount to secure its work. There is talk in Berlin of a billion dollars. Especially problematic is that Trump is doing everything possible to get a vaccine for the United States, “But only for the USA”, it is said in the German government.

“Secure” seems the most appropriate word for the German verb “sichern”. It also has the sense of save, ensure, safeguard, etc. (it’s a verb used when you’re backing up work on a hard drive or when you’re locking an outside door to a building). The “only for the USA” part, of course, is even more of a kicker. The reporter on this story (Jan Dams) had several sources in the German government for this story, and one for that particular quote, but was unable to get CureVac to respond.

Reuters has a more updated version, working off of Dams’ scoop. Their own government sources confirmed the story, for starters, but the “only for the USA” quote is still only in the Welt version. Reuters quotes a US government official as saying that the story is “. . .wildly overplayed. . .any solution found would be shared with the world”. And here is the New York Times followup a few hours later, which quotes another German government source as saying that it was “unclear whether the administration simply wanted the research work, and for any resulting production to be on American soil”. The only story with an “only for the USA” angle remains the original Welt am Sonntag report.

US Ambassador Richard Grenell said on Twitter “Not true. The Welt story was wrong.” In a better world, that might end things. But sadly, Grenell is (in my opinion) a hack who seems to have decided that his primary job is carrying water for Donald Trump no matter what, so his word is not worth very much for me. He is (and I do not use this word lightly) loathed in Germany and his opinions carry no weight at all there, either. And yes, I realize that he is also the acting Director of National Intelligence, and such is the world we find ourselves in. At any rate, his denials cannot bring an end to this story.

But what on earth is this story, anyway? It sounds like, and this is my own speculation here, someone is describing an attempt by the US government to perhaps purchase an exclusive license to whatever CureVac might discover in the coronavirus field and then restrict its use to the US (?!), or (whether it makes sense or not) to buy the company outright. I have trouble crediting either of those, honestly, but then again a lot of things have happened over the last few years that I wouldn’t have believed, either. Another problem (similar to the Grenell denial problem) is that we have seen ideas floated recently, such as one mentioned by Attorney General Barr for US money to be put into Nokia and Ericsson to make them more competitive with China’s Huawei. That wasn’t a big hit in Europe either, whatever the national telecommunications security details. So the idea of the US putting its weight behind particular European companies, or even taking them over altogether, is not so far-fetched.

It’s that “only for the USA” part that won’t go away, though, and that people won’t forget. Either this idea was actually floated by someone in the US government – and let’s be clear, such a proposal is utterly unconscionable – or someone in the German government took an opportunity to smear the US government, which would be a pretty awful move too, or someone has gotten something terribly wrong. I don’t see how we can rule any of those three out. Goddammit. I would very much like to be able to dismiss the first possibility out of hand, but (here come those opinions again) three years of sociopathic behavior from the US president and those willing to please him make me unable to quite do that.

So let’s take a look at CureVac itself. The company is a competitor in the mRNA vaccine space (which Moderna is also working in). That’s a promising field, but mRNA vaccines have yet to prove themselves in humans, so expecting one to ride to the rescue for 2019-Cov2 is asking a lot. Some readers will recall Moderna starting up a few years ago with a gigantic splash and lots of deals with larger companies, but that was all about their promised to control protein expression through mRNA pathways. More speculation here: what appears to have happened is that the company’s work in this area set off very strong immune responses in animal models, which is not so great if you’re trying to use these oliogonucleotide analogs as therapeutic agents. But the company decided a while back, I think, to make lemonade out of that load of anaphylactic lemons and go into the vaccine market, which is where they seem to have made the most clinical progress.

CureVac, though, had been in this space from the start (since 2000). Over their history, they have also been trying to produce mRNA therapeutics and to produce vaccines, but it’s been a rather long road (as summarized here at Endpoints) that has so far led to no marketed products. Their founder, Ingmar Hoerr, may well have been the first person to note the potential of mRNA species as vaccine candidates (during his doctoral work) and that led him to start the company. Most interestingly, he was replaced as CEO two years ago by Dan Menichella, and it was Menichella who was one of the biopharma executives meeting with President Trump earlier this month – the meeting, some may recall, where Trump revealed a great deal of confusion on his part about vaccines in general, and about which he later said that he told every one to do him a favor and speed things up, prompting this end-of-the-tether editorial at Science. After that summit, Menichella stated that CureVac was “very confident” that they could develop a candidate vaccine “within a few months”.

But he himself was abruptly replaced a few days ago by Ingmar Hoerr (see that Endpoints link in the paragraph above), and no one who knows is saying quite why this happened. I don’t know if there is any connection with the Welt am Sonntag story itself, but there certainly could be. At the same time, CureVac’s new urgent focus on a coronavirus vaccine would seem to be more in line with Hoerr’s strengths as well, so you can’t leave out the possibility of a sheer business decision due to wildly changing circumstances. Update: Hoerr, after nine days back as CEO, has just announced that he is taking medical leave, but the company says that this is not related to coronavirus. No one has any idea of what’s going on.

At any rate, the mRNA vaccine area for Covid-19 also has another German company in it, BioNTech of Mainz. They have announced a deal with a Chinese company (Fosun) and are moving into development of their own candidate(s) next month in China, the US, and Europe. Overall (as one can see) the path to taking mRNA vaccine candidates into the clinic is faster than traditional routes based on protein epitopes, killed-virus preparations, etc. And that’s a good thing – but only if these turn out to be plausible vaccine candidates. Which completely remains to be proven.

There’s at least a bit of room for optimism on the general idea: Moderna has been working with Merck on oncology vaccines (a field with its own complications, to be sure), but apparently the basic-immunology part of that collaboration has been going well enough so far. CureVac also had previously announced funding from the Gates Foundation (two rounds so far) for work on malaria and influenza vaccines, so presumably that was proceeding well enough for the Gates people to invest more in the idea. But we’re going to have to find out, and more quickly than anyone had planned, just how things will go against a new human pathogen in real time.

Back, then, to the story we started with. It seems very likely that the US government has been making overtures to CureVac, although we don’t know quite what these offers were. At the very least, doing this in such a stealthy manner in a country that we have such important and longstanding ties with (economic, military, intelligence and more) seems like a very bad idea. And if the reports of some sort of “USA only” clause are true – we may never know, damn it all – then that is so far beyond a “bad idea” that words fail me. At the very least, this affair does nothing but sow confusion and discord, at the worst possible time, between nations that should be working together. Someone, on some side of this story, should be deeply ashamed and probably isn’t.

Update: I should note that Moderna’s own mRNA vaccine candidate is starting its first human doses (safety testing) today. . .

72 comments on “The Curious Case of CureVac”

  1. Some idiot says:

    Thanks for the write-up! I will be watching with interest from the sidelines…

    ” to make lemonade out of that load of anaphylactic lemons”: A total and utter Derek Lowe classic…

    1. eub says:

      anaphylactically seconded

  2. James Millar says:

    On a different, but still coronavirus note: There is a story (propaganda, rather) out of Cuba that interferon β-1a is successful. Is there something nice and specific to refute that?

    1. Mike says:

      Yes, Cuba is and has always been a leader in medical research (Sarcasm) so let’s give credence to whatever their state-sponsored propaganda says.

      1. Andrew Molitor says:

        Also, interferon works on everything.

        1. James Millar says:

          Clearly. I was hoping to find something to specifically discredit this. Found one study (linked in name).

  3. Me says:

    TBF: If a ‘normal’ party was looking at doing a deal with CureVac, a possible deal would be to secure exclusive US rights.

    Or maybe i’m just making lemonade out of a different type of ‘anaphylactic lemons’?

    1. Vernon says:

      Hi Derek

      No Need to shed Crocodile Tears. it will be US tax payers money.

  4. NQ says:

    @ Me: …WTF?

  5. milkshake says:

    According The Guardian, “On 11 March, CureVac released a statement that its CEO, the US citizen Daniel Menichella, was unexpectedly leaving the firm and would be replaced by the company’s founder, Ingmar Hoerr. At the start of the month, Menichella was invited to the White House in Washington to discuss strategy for the rapid development and production of a coronavirus vaccine with Trump, the vice-president, Mike Pence, and members of the White House coronavirus task force.”

  6. G2 says:

    At least the main investor Hopp (SAP founder and investing heavily in biotech in Europe; 80% of shares in CureVac) denied that CureVac will be sold (www.sueddeutsche.de/wirtschaft/curevac-hopp-coronavirus-1.4847048) — so at least it seems that there was an offer.
    But CureVac has a subsidiary in US, however the GMP facility in Germany. It would be easier to build a new facility again rather than relocate the existing one to US. And they also claim to have portable “manufacturing machines” for the vaccine…

    1. mymagoogle says:

      Moving “portable machines” for GMP still takes a lot of time and effort. Size almost doesn’t matter, except for the size of the box to ship the “portable machine”. And then there are all the assays, and all the raw materials, and all that.

  7. In Vivo Veritas says:

    It’s just a pretty small substitution, right? USA for Deutschland?

    Deutschland, Deutschland über alles,
    Über alles in der Welt…

    1. Anno1985 says:

      Uhh, that escalated quickly…

  8. mymagoogle says:

    The world is all so odd right now.
    In any case, I had read (somewhere? when?) that there are something like a dozen or more vaccine companies working on a vaccine, of all sorts of modern means to make a vaccine. So it isn’t like CureVac is the only at all.
    The second thing that came to my mind is that BARDA is usually the USG entity that handles and coordinates these things, and I have not heard that acronym mentioned at all in anything about this matter. Doubtless they are pissed too, because it is sure hard to coordinate anything if the boss is off making other promises and plans. We all have examples of the boss doing something like that, and it hardly ever works out well.

  9. Crown my Virion says:

    The good news is Ogden Nash foresaw this:

    A mighty creature is the germ
    Though smaller than a pachyderm
    It makes its dwelling place
    Deep within the human race
    Its wims it pleases
    By causing strange diseases

    Do you my dear feel infirm?
    Perhaps you contain a germ!

  10. luysii says:

    Some good news for the antiTrumpians found on this site. The conservative press has been having a field day with Biden’s gaffes, and the pictures they show of him make him look very vague and blank.

    So as a retired neurologist (and former examiner for the American Board of Psychiatry and Neurology) with an unfortunately extensive experience with Alzheimer’s disease, I looked at the debates for 20 minutes or so, to watch Biden in action.

    He is not senile, and shows no signs of early senility. His speech is quick, focused and to the point.

    While at his age he may develop Alzheimer’s, he has no sign of it now.

    1. AlloG says:

      He’s still creepy AF and his son too- What do you say about dat from a distance neuro-King?

    2. C says:

      @luysii
      I seem to remember you predicting Hillary’s imminent death by stroke during the 2016 rounds.

      Kudos to you for not mentioning your very prestigious Harvard degree on this post though. That must have taken a great deal of willpower on your end!

      Keep licking those boots, comrade!

      1. eub says:

        Yep, the stroke “I am a professional”ing was sad.

    3. Jay Deponty says:

      Take your grandkids to meet Mr. Biden then observe!

  11. Eugene says:

    Does anyone really think that if a vaccine for Covid-19 were available that any company would be allowed to make it exclusive to one country. If a billion dollars is being thrown around for this you can be sure that terms and conditions would have been examined in minute detail. The reason Reuters did not repeat the USA only assertion is that they still have a small shred journalistic integrity left and will not report an assertion that cannot be proven, at least in this case.

    1. I agree 100%. I’ve had friends ask me “Oh! That company create X for Coronavirus. They’ll make so much money!”

      If the company is even slightly in tune with the public’s view of biopharma, they’d quickly realize that they are probably going to be giving the product away or selling it at cost. Even a hint of high profitability will cause the world to come crashing down on that company. Countries will ignore the patent and produce it themselves. Governments will apply strong pressure to keep prices in line.

      That said, I think it would be a PR boon for any company that made advances against Coronavirus, but profitable? Probably not.

    2. MikeC says:

      Absolutely true – but this could still have been Trump’s plan. By the time the plan was filtered through more rational people, it was probably more to have US ownership, a second research site in the US, and one of the first production sites located in the US. This way Trump could claim that he cured Covid-19, and make certain that no other country had access to the vaccine before the US.

      1. loupgarous says:

        Having production sites for essential pharmaceuticals and API sited here to as great an extent as possible may not be globally altruistic, but it makes sense in the context of the recent recalls of various drugs from overseas factories for contamination with nitrosamines and other undesirable ingredients. It also makes FDA inspection stronger and more feasible across the board.

        In the meantime, let’s look at another reason to whistle drug production for our market back home. If China was selling adulterated API (like the sartans) to us from venality and carelessness before, they seem to be stirring up support for organized hostility toward us now.

        When the mâitre d’ and waiters at a restaurant give you the stink-eye as they seat you and slam the silverware and platters on your table, it’s time to find another restaurant before someone puts offal sauce on your appetizer.

    3. jim grazis says:

      i do believe trump could envision such a plan.

  12. jz78817 says:

    Hi Derek,

    have you heard some of the rumblings out of Europe correlating severe symptoms in younger patients (18-44) with use of NSAIDs for managing fever?

    1. Druid says:

      There is a publication from France in 2016: “Nonsteroidal Anti-Inflammatory Drug without Antibiotics for Acute Viral Infection Increases the Empyema Risk in Children: A Matched Case-Control Study”, and a review from France in 2019: “Risks Related to the Use of Non-Steroidal Anti-Inflammatory Drugs in Community-Acquired Pneumonia in Adult and Pediatric Patients”. These seem to indicate that NSAIDs (but not acetaminophen) interfere with the inflammatory response leading to a near 3-fold increased risk of bacterial lower respiratory tract infection. So, I will not be tempted to treat the fever with NSAIDs, but I will look for some paracetamol (there may already be a shortage in UK). Thanks for bringing this up.

      1. Bannem says:

        I thought this was common knowledge in the field . . . a friend of mine has severe COPD, and pretty much the first thing they told me about their condition was that they are unable to take ibuprofen as it exacerbates their illness. Paracetamol (acetominophen) is OK though . . .

    2. anon says:

      ACE2 (the target that Covid-19 coronusvirus attacks) has been shown to increase after administration of thiazolidinediones or ibuprofen.

      See: Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? Lei Fang; George Karakiulakis; Michael Roth
      Lancet Respir Med 2020; Published Online; March 11, 2020

  13. mallam says:

    Instead of trying to come up with some scheme such as this one, the administration should be coordinating with all companies capable of large scale manufacturing of vaccines (most likely to succeed will the a traditional version, not RNA based) to make as much and as fast as possible for one proven effective for distribution not only in the US but throughout the world, with the cost of manufacturing to be picked up by the government. Not only would this help ease this crisis and any threats in the future by this virus, but also provide good will across the globe.

    1. loupgarous says:

      How about a BARDA Grand Challenge, teams of intrepid virologists and molecular biologists competing for world-wide fame and beaucoup money?

  14. Mister B. says:

    Why do vaccines have to use mRNA technologie instead of “classic” flushot, with inactive patogens ?

    It may sound naive, but it could be a good entry point to find a Corona-vaccin.

    1. M says:

      AFAICT there are multiple techniques underway, including the classic approach, but the mRNA seems to be easier to design and scale up for testing–which is why it’s in the news now. If it works, great, if not we’ll have more trials pending.

  15. tlp says:

    Is truth volatility a legit term yet?

  16. Dr. Manhattan says:

    If I had to bet (as a microbiologist) on a successful vaccine, I would go with some of the more traditional approaches rather than the (as yet to be proven) mRNA route. Both Moderna and CureVac seem to be taking a similar approach, and has been discussed here before, there are still a lot of questions about mRNA delivery and efficacy. I wish them well in this effort, but I would place my money on the more traditional routes of antigen presentation to mount an effective vaccine response.

    Also, if we already have Moderna working on a similarly mRNA strategy, why the sudden courting by the Administration of CureVac? Is this yet another example of the chaotic, wildly impulsive response of the senior Administration?

    1. qetzal says:

      That was my thought as well. Of all the things one might throw money at, a company that’s been trying for 20 years to develop vaccines using an unproven technology would be very far from my first choice.

      Not that I don’t wish CureVac success!

    2. loupgarous says:

      Hopefully, that billion dollars Trump was reportedly waving at CureVac’s owners wasn’t part of the recent Congressional appropriation for coronavirus measures.

    3. Hap says:

      CureVac was cheaper and more amenable to a deal?

    4. According to a piece in the UK online press last weekend (and picked up by Reuters), CureVac are hoping to leverage the “success” (Phase I healthy volunteer study) of their low dose CV7202 rabies vaccine (2 doses of 1ug). If a COVID-19 mRNA vaccine proves protective at the same dose, the existing German facility could manufacture up to 10 million doses per campaign in their existing facilities. Still way short of what would be required even on a restricted higher risk initial deployment (as per existing WHO pandemic guidelines).

      The Moderna mRNA-1273 vaccine Phase I is in a dose escalation study, running from 25ug to 250ug, so even with success at the low end, that’s a big difference in mRNA requirement.

      Of course, no way of telling whether mRNA will be the way to go, and having worked in and followed vaccine development for decades, it’s been more evolution than revolution. One bright spot is that there appears to be a high degree of conservation with well studies SARS B-cell epitopes, so perhaps some of the false trails might be recognised at an early stage, for example, avoidance of antibody-mediated enhancement.

  17. Calvin says:

    So this is not the first time this situation has happened. During the 2014-15 Ebola outbreak, the NIH threw it’s weigh around (with clear government backing) in a similar way where they were expecting exclusivity for the US if there was a major outbreak in. The EU authorities and EU funders obviously made sure that their funding went elsewhere and lots of contractual safeguards included. It was not pretty.

    One issue is that NIH funding often comes with step in rights around US manufacture and use. So this is not unique to Ebola or COVID19.

    At the end of the day, these RNA vaccines are unlikely to work, or will require a lot of luck to work. I wish them well, but the likely outcome of that one of the more traditional approaches will work. Even then, respiratory viruses are the place vaccines got to die. We can cover flu a bit, but the rest of these acute viral infections have not been met with much success with the vaccine approach.

    Good luck to all.

    1. Jim says:

      “One issue is that NIH funding often comes with step in rights around US manufacture and use. So this is not unique to Ebola or COVID19.”

      Almost all government funded research performed by universities in the US is subject to the Bayh-Dole act, which lets the university retain the rights, but gives the government a fully paid, royalty-free, non-exclusive license to use the invention. All licenses of that technology to others must include a “marching in” provision that allows the government to have someone else practice the invention. This is to prevent someone from buying up the rights and putting it on the shelf in the event of an emergency. The marching in provision has some pretty strict limitations.

  18. Charles H. says:

    Given everything that’s been said, I’m going to guess that Trump wanted exclusive control over distribution in the US. Possibly to go to one of his friends companies. And that it was garbled by translation at some point.

    But yeah…the way the US government has been acting the more extreme scenario is unfortunately believable, and many won’t doubt it.

    1. loupgarous says:

      “For the USA’s use only” hasn’t shown up anywhere but Welt am Sonntag. Usually, European newspapers aren’t willing to be scooped for long on a juicy story like Trump secretly trying to bogart all of CureVac’s product for Americans only. Lots of corroboration by other news sources on every other facet of this story, but not this. There are plenty of other missteps by this administration to seize on a Sunday morning broadsheet’s accusations that aren’t corroborated anywhere else. That particular accusation looks like the meadow muffin that didn’t stick to the wall.

      1. Guybrush Threepwood says:

        The NYTimes and Washington Post as well report about it and several ministers of the German government as well as Merkel explicetly confirmed it. There even was a out-of-schedule national security meeting on that topic on Monday as this approach of the US government is seen as an extremely unfriendly act. The G7 meet on the topic as well and pressured the US administration on Tuesday to refrain from this goal.

      2. Hap says:

        If the German government believes it, whether or not it’s a cow patty, it would be a good time to explicitly deny it (both publicly and privately); if the Administration can get private contacts, then those might have a better chance of convincing the German government and then they can explain it at home. Trump may not have much credibility but others might.

        It seems hard to deny, though, that Trump has had a Gore Vidal view of winning (as Dr. Lowe noted in the Periodic Bagel).

  19. anon says:

    Moderna up 25% today

  20. Kevin Sours says:

    The Administration is starting to find out the price you pay for squandering your credibility. They can deny what they want, but they’ve denied so many things that turned out to be true that they’re word is without value.

  21. CureVac Fake says:

    The story is quite murky. The original article cites an anonymous source from the German Ministry of Health. Nothing else. No comment from CureVac or Dietmar Hopp (main investor). Major uproar. Then Hopp told Sport 1 that he was informed by someone from CureVac about the offer and that he would not sell it. German government announces, that it would offer CureVac financial support, if they do not agree.
    Today, CureVac made clear, that the company never received such an offer.
    BUT: Also today, CureVac got a 80 million loan from the European Union!! What for?? For a rejected offer, that never existed?? Why has Hopp not put in more money if he is convinced??
    Something is really fishy here? Who would benefit from such a story?? Anyone else beyond CureVac?? The newspaper should publish the source (if there is one).

    1. Guybrush Threepwood says:

      The German minister of interior Horst Seehofer confirmed the information publicly and Angela Merkel explicetily refered to it in a press conference Tuesday evening. The information is trustworthy. As well, the G7 stepped in and pressured the US administration not to monopolize vaccine research.

      1. CureFake says:

        If you read the news and listen closely, it all comes back to a single anomymous source in the “Welt am Sonntag”. The only one saying, that he has heard from someone within CureVac is Dietmar Hopp in his interview on Sport1.
        And the company made clear, that there was no offer at all??
        So?? Who is talking to Dietmar Hopp from CureVac (I would guess not a technician).

  22. Get Real says:

    I hate to be in the curious and uncomfortable position of defending Trump, but…

    Come on, the assertions here are ridiculous. Either people are mistranslating, or people are deliberately making up stories.

    What possible value would there be to buying a cure technology only for the US? That makes no sense at all, unless you are a bad actor nation. Perhaps Curevac wants royalty payments for every territory where the vaccine is used, and the US indicated that we would only pay for the US.

    But assuredly, the US wasn’t trying to lock up the vaccine only for the US. It strikes me that people who will believe this will believe anything. That’s not a good look for scientists.

    1. eyesoars says:

      Unfortunately, the story is quite believable given Trump’s past. Doesn’t mean it’s true, but… One of Trump’s more juvenile traits is that winning to him is seeing someone else lose, or at least lose more than he does. Win-win is not part of his beliefs or experience: everything is a zero-sum game (or worse).

      1. Get Real says:

        See…THIS is why people are sounding like fools.

        “I hate Trump” ==> “He might do this” ==> “He did do this”

        No, there are plenty of reasons to hate Trump, but none of those are consistent with this.

        Whoever made up this story (and the more I think about it the more I believe this was intentional misdirection) is relying on people’s hate of Trump to lead them down that path.

        Stay sane.

        1. Vader says:

          Scientists are not notably saner than other people.

          In fact, indications are the contrary, at least for certain values of “sane”.

  23. Guybrush Threepwood says:

    Just to give you an impression, in which situation this news fall: In Germany, everything has been knocked down completely. I cannot remember a situation like this in my whole life so far. Schools and Kindergartens are closed for 6 weeks (all my school based studies failed as a consequence), all public buildings, sport facilities, playing grounds, all shops except for daily life necessities … Bavaria just declared a state of emergency for the next two weeks. All borders are closed to Austria, Switzerland, Czech Republic, Denmark, Poland and France – so essentially 90% of the borders. Flights have been stopped almost completely. In university, teachings have been stopped, the libraries are closed and it might be that the building will be locked in the course of this week. All scientific conferences have been cancelled or postponed. People currently start to freak out a little bit with hoard purchases and weird situations in the super market with empty shelves (people are hoarding toilet paper! unbelievable!).

    In a time like this, the news about monopolizing vaccine causes an enormous outrage. Multiple highly credible sources have publicly confirmed the news report and as far as I can see, the “only for the US” information is valid. It is hardly possible to overestimate the damage, this does to the relationship between European countries in the US. Trump never has been popular in Germany, but now people view the current US administration as an immediate personal threat to their life and their health.

  24. Anonymous says:

    Has anyone found a good article comparing mRNA vaccines to killed or weakened virus vaccines? I know that I have some questions.

    Assuming that a whole virus based vaccine resembles the live virus, it would be a big sphere with MANY spike-like proteins and glycoproteins sticking out from the surface. Usually, the host’s immune system makes an assortment of antibodies to those spikey things, some more effective than others. I read someplace that SARS-CoV-2 surface protein trimers are particularly antigenic. Key thing: the “bottoms” of the spikes are buried in the membrane and not exposed to the immune system to produce antibodies. Anyway …

    In the mRNA vaccine, the host is injected intramuscularly with mRNA that codes for a specific piece of protein (the mRNA is packaged in liposomes). The Moderna mRNA codes for the Spike (S) protein. The vehicle (liposomes) gets the mRNA into the muscle cells and those cells start to produce the S protein that, somehow, gets exposed to the immune system.

    (So far, so good? Please correct my mistakes!)

    Q1. Is the Moderna S protein expressed on the surface of the transformed muscle cells or is it secreted / soluble?
    Q2. If surface bound, do they know if it is buried in the membrane right side up? Is it possible that the polar head is intracellular and the trunk / roots are in the membrane or sticking out extracellularly to generate the “wrong” immune response?
    Q3. If Spike protein is secreted / soluble, isn’t it also possible that the trunk / root can now be exposed and be able to produce an antigenic response that is irrelevant to the “live” virus proteins?

    Q4. In the case of all new vaccines, I think there is a danger of priming the host to have a hypersensitive response when the real virus comes along. Is that more or less likely to happen with an mRNA vaccine?

    Thank you for answering Qs and clearing up any really bad suppositions.

    1. Alan Goldhammer says:

      I don’t have the answers but I will note that there is a good summary from a Mayo Clinic symposium on Zika Virus vaccine: https://www.mayoclinicproceedings.org/article/S0025-6196(19)30483-5/fulltext#sec4

      IMO, fuller testing of the Zika vaccine including the mRNA and/or DNA vaccines for safety and efficacy would have given us a step up in the R&D race to get a COVID-19 vaccine out. Safety and potency issues based on the platforms would be better known. I have skepticism about the mRNA vaccines as well. What I don’t want to see is an egg-based production platform that is used for seasonal flu. They really need to be able to reliable produce antigens in cell culture.

      Most of the major vaccine companies are engaged in research. IMO, the US government should enable cross company collaboration by an explicit anti-trust waiver.

    2. Barry says:

      Good questions.
      The expectation is that the viral protein (or rather fragments of it) will be displayed on the muscle surface by MHC1. The complex of a foreign peptide on MHC1 would then stimulate a T-Cell immune response.
      But since an mRNA vaccine would not put the free antigen into the plasma compartment, it might not provoke a B-Cell response.

    3. Decent recent (open access) review in Nature for you or anyone interested in the field here:
      https://www.nature.com/articles/s41541-020-0159-8

  25. Terry says:

    Anyone notice this statement from CureVac on Twitter:

    CureVac
    @CureVacAG
    ·
    Mar 16
    To make it clear again on coronavirus: CureVac has not received from the US government or related entities an offer before, during and since the Task Force meeting in the White House on March 2. CureVac rejects all allegations from press.

    1. Get Real says:

      That is pretty definitive.

      So now you either have to believe the company itself and also rely on Occum’s razor, which suggests the story is false.

      Or you let your hatred of Trump lead you to ridiculous conclusions that make no sense. In which case, you become part of the problem.

      1. Hap says:

        US entities like me have lots of reasons to dislike Trump (though I’d like to think that I wouldn’t have to lie to get him gone). Why the Germans, though? He hasn’t been great at playing with others, but it seems like a bigger jump for the German government and Germany as a whole to assume that he would be screwing them over, particularly with denials from the company.

        It’s also problematic from a foreign relations view – just as it was problematic for someone to release Trump’s diplomatic phone conversations, messing with allies to get rid of someone you don’t like or fear is a problem, because your (presumed) allies won’t know if they can trust your word later. I’d like to think that there is a 3rd party fragging us, but that is assuming too much of political nature to be that generous.

  26. Landon Davis says:

    People, c’mon now… we know Trump by now! The alleged plan involving buying Curevac makes perfect sense, including the part about “just for the USA.” But not in order to prevent the world from having it — Trump just wanted to make sure HE was the one who would be seen OFFERING it to the world. If the US Gov. had sole ownership he could literally *stage* a huge press event where he would hand it off to allies, and maybe even use it as a bargaining chip behind the scenes to secure further political gold from troublemakers like Kim Jung Un. For one who thinks like Trump, the possibilities are like heroin, crack and meth all rolled into one.

    1. Gutfried Q says:

      Yep, and the same goes for germany. There are press articles where some governmet guys take pride in telling that this drug is developed for the whole world. A narcistic farce, given the potential hurdles.

  27. Hopeful D says:

    Has anyone addressed the cost of a mRNA vaccine. I read that Moderna’s clinical trial is dosing at 10, 100 and 250 ug. That’s going to require a lot of NTPs. Can they produce tens of millions of doses?

    1. I’ve been doodling around with this as part of a funding proposal. There’s a wealth of pandemic associated literature and working assumption is around $25 per vaccinated individual, not that far off the current acquisition cost of ‘flu vaccine.

      Moderna have stated that, should they be able to bring a vaccine to the party, pricing would be in the range for existing respiratory vaccines. Given that Prevenar 13 is around $500 per course (public acquisition cost, $800 privately), that’s a big range. I’ve seen one investment analyst estimate $600 per course. Not clear whether he or she was running a fever at the time of writing….

  28. luysii says:

    C & Eub — Surely you took my advice in my post of 27 January ’20. You know “What to do about the Wuhan flu? The short answer is to lay in a month or two of dried food and drink, and have plenty of bottled water around.” and “Some individuals are what is called ‘superspreaders’ ” No? Too busy snarking? Read it now and good luck, you’ll need it — https://luysii.wordpress.com/2020/01/27/what-to-do-about-the-wuhan-flu/

    1. eub says:

      No, I regretfully gave up reading your blog for the good bits since it wasn’t worth the time for the rest, but the likelihood of a pandemic was pretty clear as soon as we saw this was showing community spread that evaded counter-SARS-CoV-1 measures like fever checks.

      Hope you can get off the Fox and come out the other side, since you do have merits.

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