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Re: Vaccine efficiency

Posted: Wed Mar 10, 2021 5:50 pm
by guy153
Splatt wrote: Wed Mar 10, 2021 2:11 pm My main issue with it technically is they still don't seem to have fixed the
issue of vector derived immunity which means we're not "learning" the spike as
well as intended and booster doses are even less effective again. Also likely
why Sputnik which is essentially the same thing but 2 vector seems to be more
effective and why AZ are doing mixed trials. Most AZ protection against severe
disease i guess is derived from the T cell responses. The notably very large
different in protection against *infection* between AZ and Pfizer (60 v 90%) is
probably a result of the vector approach in my view.
Yes that seems pretty likely. AZ are using the largest of the 3 doses they
tried in for the equivalent MERS vaccine. Sputink uses double that! This may
also be why it has greater efficacy against infection.

I know AZ apparently better if you paradoxically use a low dose for the
first one but I'm not sure I really trust that result. They may have just been
fishing around in the data a bit to make the vaccine look better.
Splatt wrote: Wed Mar 10, 2021 2:11 pm Its not a placebo but if the focus is now on "cases" its not going to be
anywhere near as useful in bringing down cases.
They're also going to have to stop counting deaths as "died within 28d of a
positive test" because that will really make AZ look bad. It has no effect on
whether you become asymptomatic positive.

Re: Vaccine efficiency

Posted: Wed Mar 10, 2021 6:16 pm
by Splatt
guy153 wrote: Wed Mar 10, 2021 5:50 pm Yes that seems pretty likely. AZ are using the largest of the 3 doses they
tried in for the equivalent MERS vaccine. Sputink uses double that! This may
also be why it has greater efficacy against infection.
I don't think its so much dosage but more of a vector issue.
Vector-derived immune response has been an issue for viral vectors for a long time. We tried it in gene therapy with similar disappointing results (before things like CRISPR took over).

Sputnik at least being a dual vector approach means the booster stands less chance of being blasted by the immune system more than the spike part itself.
AZ are trialling this in Russia with mixed doses so its possible they see it the same way.

Another suspect pointing to this being the cause is the low increase in efficacy for dose 2 over just a single dose and the fact the longer we leave it the better it seems to be.

Long term wise i can see this potentially be an issue if they move to annual updated boosters as well unless they regularly cycle the vectors.
I know AZ apparently better if you paradoxically use a low dose for the
first one but I'm not sure I really trust that result. They may have just been
fishing around in the data a bit to make the vaccine look better.
The data wasn't great for sure (look at those CIs !) but thats the case for the entire AZ.
The trial tried to do too much with too little samples and fairly narrow demographics which is why there are certification issues.

That said, there *IS* a low dose signal there at the moment with the current analysis. Again it might be a lower initial dose isnt causing the immune system to react as strongly to the vector so the second dose hangs around a bit longer to be learnt from (yes, simplifying).
Maybe they can tweak the response by playing with the adjuvants a little but ultimately i think the Sputnik approach of varying vectors might yield better results long term.


Again we did sort of notice this trying a similar approach with gene therapy.
They're also going to have to stop counting deaths as "died within 28d of a
positive test" because that will really make AZ look bad. It has no effect on
whether you become asymptomatic positive.
That's a measure that's entirely unhelpful for anything except trying to argue for continued restrictions. Again, we've never done that before so why now?

If the goal is to stop people becoming seriously ill or dying then Pfizer and AZ both do the job superbly well.
We were TOLD once that happens its game over. We win.

As you said though, if cases remain, people will still be dying "within 28 days" of testing positive even if they had no idea they WERE positive but these will still be' covid deaths'.

However the disturbing trend recently is towards the zero-covid insanity and we've switched to "cases" instead (and worse, define a case as someone PCR positive with no symptoms).
With a 80%+ AZ approach in the UK its very unlikely to drive "cases" low enough for their liking.

The view now is "Cases are bad, They might produce a variant. Oh look! A variant! Better drive cases lower" which could ultimately mean restrictions in place for a virus that nobody is dying or getting seriously sick from at all. Which is insane.
There's a real danger of us solving the problem and not actually realising its been solved.