• The Cycling News forum is still looking to add volunteer moderators with. If you're interested in helping keep our discussions on track, send a direct message to @SHaines here on the forum, or use the Contact Us form to message the Community Team.

    In the meanwhile, please use the Report option if you see a post that doesn't fit within the forum rules.

    Thanks!

Coronavirus: How dangerous a threat?

Page 255 - Get up to date with the latest news, scores & standings from the Cycling News Community.
With the first trial data, AZ also turned it into a PR-event by merging the main trial with one that had gone wrong but accidentally produced better protection. Back then, the real efficacy was 61% iirc, not the 70% they wanted the headlines to be. They have consistently oversold their product, both the efficacy and the output they're able to handle.
Agreed. At the end of the day, their original sin was choosing the wrong conformation for their antigen at the design stage. A small but significant difference that makes their product that little bit less protective than their competitors. So, to keep up with the Joneses they play a little loose IMO with the numbers. The sad thing is that their vaccine is effective, just not quite as good as the others. That in itself is still an immensely valuable product, but the damage to their credibility (much of it the self-inflicted variety) is really problematic.

Scientists believe that for COVID-19 vaccines to be effective, our immune systems must develop antibodies that prevent this fusion. Such antibodies must target the spike protein in its aptly named prefusion conformation. Unfortunately for vaccine developers, spike proteins are liable to spring from their stubby prefusion shape into their elongated postfusion form on a hair trigger.
Fortuitously, Graham and a former postdoc, Jason McLellan, devised a solution to this problem before the pandemic. Through a bit of structural biology and persistent protein engineering, McLellan discovered that adding two prolines—the most rigid of the 20 amino acids—to a key joint of a vaccine’s spike protein could stabilize the structure’s prefusion shape. This 2P mutation worked in preclinical studies of Graham and Moderna’s MERS vaccine, so they applied it to Moderna’s COVID-19 vaccine.
Other companies, including Johnson & Johnson, Novavax, and Pfizer, are hoping the 2P mutation works for their COVID-19 vaccines too.
The 2P mutation might quite literally be the smallest detail that could make or break the first generation of COVID-19 vaccines. It’s an easy enough tweak to add during the early stages of vaccine design. And if successful, 2P-based vaccines may herald a new generation of vaccines whose molecular makeup is fine-tuned to craft a safer, stronger immune response.
Even if they are, the 2P mutation won’t be the only reason, and it might not even be the most important. One of the COVID-19 vaccine front-runners, produced by AstraZeneca, doesn’t even use it.

As for the production part, I would really love to read a deep dive into why it has been so tough to make their vaccine. Other companies have had their issues too, but AZ seems to really be struggling. I guess it could be lack of experience in the field.
 
This is from Reuters:

 
  • Like
Reactions: jmdirt
  • Like
Reactions: Keram and jmdirt
Last sentence made me smirk. So now the UK is prepared to let us have some of the AZ vaccine produced in a EU factory. How nice of them.

But then, greed is good, apparently:
 
Last edited:
It is interesting that the German wave is now about equivalent to the current USA plateau with vastly different reactions. In the US, we have about declared victory over COVID with restrictions loosening left and right while Germany is debating whether to fully lockdown. This is why vaccines are in such demand. It is the pathway out of this.

 
  • Like
Reactions: Koronin and jmdirt
So, on the developing AZ story, this is how it went according to insiders:
  • AZ purposely delayed asking for permission from EMA for its Dutch production plant while it already had asked for UK permission, so that it could prioritize the UK even from a EU production site
  • from this Dutch plant, vaccines were sent to Italy for filling/bottling
  • the idea was to then send large batches to the UK, skipping the EU and Covax
  • this plan was thwarted by the EU's decision early February that forced producers to ask for permission to export vaccine out of the EU
  • since then, the stock has only gotten bigger, lying there unused
  • now, there are about 29 million doses of AZ vaccine in the Italian plant
  • this about double the amount AZ has delivered to the EU so far (though the promised Q1 deliveries amounted to 100 million)
  • the EU only found out because EU commissioner Thierry Breton became suspicious of what happened with the Dutch facility's produced vaccine (AZ CEO only gave vague answers)

Crazy and really shady stuff.
The UK seem intent on a clash with the EU - on this and other stuff - purely for electoral reasons (look at the EU struggling! Brexit best ever! etc.). Somehow, they managed to play puppet master at AZ.
 
  • Sad
  • Angry
Reactions: Koronin and jmdirt
So, on the developing AZ story, this is how it went according to insiders:
  • AZ purposely delayed asking for permission from EMA for its Dutch production plant while it already had asked for UK permission, so that it could prioritize the UK even from a EU production site
  • from this Dutch plant, vaccines were sent to Italy for filling/bottling
  • the idea was to then send large batches to the UK, skipping the EU and Covax
  • this plan was thwarted by the EU's decision early February that forced producers to ask for permission to export vaccine out of the EU
  • since then, the stock has only gotten bigger, lying there unused
  • now, there are about 29 million doses of AZ vaccine in the Italian plant
  • this about double the amount AZ has delivered to the EU so far (though the promised Q1 deliveries amounted to 100 million)
  • the EU only found out because EU commissioner Thierry Breton became suspicious of what happened with the Dutch facility's produced vaccine (AZ CEO only gave vague answers)
Crazy and really shady stuff.
The UK seem intent on a clash with the EU - on this and other stuff - purely for electoral reasons (look at the EU struggling! Brexit best ever! etc.). Somehow, they managed to play puppet master at AZ.
It doesn't seem like AZ is the most 'honest' company. Their 'games' may end up costing them (in several ways).

IMO pharma companies in general have three priorities: 1) make huge profits, 2) make huge profits, 3) make huge profits. The only reason they even care about improving peoples' lives is to ensure huge profits. I was hoping that a pandemic would bring out the best, and maybe has in some cases, but...
 
  • Like
Reactions: Koronin
So, on the developing AZ story, this is how it went according to insiders:
  • AZ purposely delayed asking for permission from EMA for its Dutch production plant while it already had asked for UK permission, so that it could prioritize the UK even from a EU production site
  • from this Dutch plant, vaccines were sent to Italy for filling/bottling
  • the idea was to then send large batches to the UK, skipping the EU and Covax
  • this plan was thwarted by the EU's decision early February that forced producers to ask for permission to export vaccine out of the EU
  • since then, the stock has only gotten bigger, lying there unused
  • now, there are about 29 million doses of AZ vaccine in the Italian plant
  • this about double the amount AZ has delivered to the EU so far (though the promised Q1 deliveries amounted to 100 million)
  • the EU only found out because EU commissioner Thierry Breton became suspicious of what happened with the Dutch facility's produced vaccine (AZ CEO only gave vague answers)
Crazy and really shady stuff.
The UK seem intent on a clash with the EU - on this and other stuff - purely for electoral reasons (look at the EU struggling! Brexit best ever! etc.). Somehow, they managed to play puppet master at AZ.


WOW. At least there is an actual stated reason why there is a bunch of A.Z. doses sitting in the US. Now we can argue over the reasoning, but at least there is an official/real reason, although it's more a US Govt reason than anything else. Still think we need to ship more of the A.Z. doses that are sitting in that warehouse to Canada and Mexico than keep it sitting there.
 
Going for dose #2 of pfizer tomorrow afternoon. This is the part from the consent form that I alluded to a while back when the topic was the blood clots. It does basically say that just about anything can happen. I'm fine with that. Benefits and risks etc....

I understand there may be additional unknown risks to the COVID-19 vaccine.
I understand that the side effects listed above may not be all the side effects of the COVID-19 vaccine as the vaccine is still being studied in clinical trials. I understand that the long-term side effects or complications of this vaccine are not known at this time.
 
  • Like
Reactions: Sciatic and jmdirt
Going for dose #2 of pfizer tomorrow afternoon. This is the part from the consent form that I alluded to a while back when the topic was the blood clots. It does basically say that just about anything can happen. I'm fine with that. Benefits and risks etc....
That’s right we’re on almost the same schedule—I got Pfizer shot #2 this morning, and that feels like an accomplishment getting that done with. A little leery about the next two days though, since I had a fair amount of flu-like symptoms that started about 36 hrs after the 1st shot, and reactions to the 2d are sometimes worse. Well worth it though, and if I’m laid up by Friday I have both E3 and Catalina to watch, and Sweet 16 games on Sat :) Hope yours goes smoothly.
 
It is interesting that the German wave is now about equivalent to the current USA plateau with vastly different reactions. In the US, we have about declared victory over COVID with restrictions loosening left and right while Germany is debating whether to fully lockdown. This is why vaccines are in such demand. It is the pathway out of this.

Unfortunately the US has had a 2percent rise in cases over the past week, and our flare have tended to come after those in Europe. The good thing, which would seem attributable to vaccinations, is a continued drop in death rates and hospitalizations here.
 
The thing is that AZ was completely wrong to promise UK factories as back-up in the EU contract, while they also stated in the UK contract these same factories would only produce for UK. Moreover, they seem to have used a random number generator to decide on how many vaccines to promise to all their customers.
 
  • Like
Reactions: Koronin
Yes, it's obvious that AZ was not transparent in the process of negotiations, no disagreement there.

However, I do feel that more due diligence should have been done (yes, it's easy to say so in hindsight, but given the importance of the matter it's not unreasonable),
 
Unfortunately the US has had a 2percent rise in cases over the past week, and our flare have tended to come after those in Europe. The good thing, which would seem attributable to vaccinations, is a continued drop in death rates and hospitalizations here.
It is ticking up in a lot places here. Maryland has seen an increase since the restaurant capacity restrictions were removed a couple weeks ago (just in time for St. Patricks day and March Madness). Michigan, Massachusetts, and a lot of the Northeast (where it is still chilly) is also seeing a significant increase. Hopefully the vaccines will blunt the full effects of people returning to normal a little prematurely, but we really need a lot more 3m dose days if we want to avoid another little wave.

View: https://twitter.com/KagroX/status/1374914991237775365
 
The article doesn't shed a lot of light on the details, but one of the mutations (l452r) does not do much on its own, although it is a tad more resistant to neutralizing antibodies. The other one is e484q, which is similar to the variant from South Africa, which is the mutation that really makes it worse than the UK variant in terms of antibody neutralization. I would imagine the double mutant is likely to be worse than the prevailing strain, but I would bet that the vaccines are still effective against it unless it has more going on that they don't mention. They don't really specify if there are mutations associated with increased infectivity (independent of immune evasion).
 
Last edited: