Coronavirus

[bkp_duke]

Can't open the article but I have read other sources that the "big" gap is @ 5%. However, wouldn't that be an argument for opening up a booster shot to more people? Maybe over 50 years old? I understand not wanting to rush to give to people under 30 - especially males.
Although again it is sad that probably the only reason we are having this conversation is because there are so many people who refuse to get vaccinated.

Relevant part of the article:
"Data collected from 18 states between March and August suggest the Pfizer-BioNTech vaccine reduces the risk of being hospitalized with COVID-19 by 91% in the first four months after receiving the second dose. Beyond 120 days, however, that vaccine efficacy dropsto 77%.

Meanwhile, Moderna’s vaccine was 93% effective at reducing the short-term risk of COVID-19 hospitalization and remained 92% effective after 120 days."

Basically, after 4 months, Moderna is providing substantially better protection (and we saw this in the early trials as well, so this is not a surprise). Given how much more mRNA that the Moderna shot has in it, this is not surprising (antibody titers are usually "dose dependent).

Lot more than the "5% difference" you heard.

And no, I don't, nor have I ever, owned Moderna (or Pfizer) stock. I'm pretty much all in on TSLA.


EDIT - and this data is actually a strong argument AGAINST booster shots for those that got Moderna vaccines, while a reasonable argument can be made for boosters for those that got Pfizer, especially in "at risk" populations.

 

[bkp_duke]

SIDE NOTE:
If we are really considering boosters, they should be re-formulated with the sequence of the Delta variant. I don't know what that means for FDA approval (would they have to be trialed like the originals, or could they be fast-tracked like what we do with Seasonal Influenza shots?).

Just my 0.02 of the subject of "well, if we are going to do boosters, might as well maximize their effectiveness".

 

[Norbert]

SIDE NOTE:
If we are really considering boosters, they should be re-formulated with the sequence of the Delta variant. I don't know what that means for FDA approval (would they have to be trialed like the originals, or could they be fast-tracked like what we do with Seasonal Influenza shots?).

Just my 0.02 of the subject of "well, if we are going to do boosters, might as well maximize their effectiveness".

Do you think it is also possible to improve the long-term effect? Perhaps 2 versions, one for above 65, and one for below 65?

 

[AlanSubie4Life]

Lot more than the "5% difference" you heard.

Yes, Moderna nearly 3x as effective (8% vs. 23%). And this was against hospitalization…

From the way the study was set up, it is hard to argue confounding, etc. But of course there’s always a small possibility.

The difference is remarkable, given the initial antibody titers being fairly similar and it would be nice to know exactly why! Would have been nice to see more data over time on titers for data from patients gathered in a similar fashion (rather than from a totally different study which might create confounding due to selection criteria, etc.)

As the MMWR speculates:
1) Size of dose? Better lasting response?
2) Interval between doses? Better lasting response? Better cell-mediated response?
3) Something about the type of antibody response, specifically to Delta?

If we are really considering boosters, they should be re-formulated with the sequence of the Delta variant

Pfizer thinks this is not necessary (since Delta does not really escape immunity), but I do really wonder about their motives, and it does seem like it makes sense to “move the goalposts” from time to time, along with the virus, to keep as similar as possible target to what is in circulation. Bedford thinks it would be a good idea, and it would be annoying to have to scramble to keep up…

And if you’re boosting it seems like it’s a good opportunity for a little hybrid immunity.

Anyway, seems like we still don’t know for certain what the difference is.

If it’s just the interval, then the boosters for Pfizer will be highly effective and perhaps long lasting. If the dose is important though, Pfizer could wane again. If it’s somehow a targeting that is somehow not picked up in the neutralizing titer (like some weakness in the cell-mediated response to Pfizer), waning again could be a problem.

Obviously could be some combination of factors too, or some other specific difference.

Wonder whether Pfizer has a good guess? I guess we’ll know more in a few months after the boosters have time to be tested.

 

[AlanSubie4Life]

Also, no idea if it’s possible that the epitopes targeted by cell-mediated immunity could be better targeted for Moderna than they are for Pfizer. I know the spike sequences are not identical, and epitopes targeted for cell-mediated immunity are different than those targeted by the neutralizing antibodies (I think?). That would show as increasing rates of hospitalization as neutralizing titers from humoral immunity wane…maybe?

If it is even theoretically possible (and not an immunologist so I have no idea), that would be bad, since it would mean consistent boosting would be required for Pfizer - while perhaps not for Moderna. In theory humoral immunity could wane for Moderna, and infections could rise, but if the cell-based response is better targeted for Moderna, that would keep hospitalization rates down regardless of increased infection rates because the second barrier is more effective.

Hopefully this is not the reason! Makes me wish I had waited for the Moderna mix-and-match!

 

[bkp_duke]

Do you think it is also possible to improve the long-term effect? Perhaps 2 versions, one for above 65, and one for below 65?

Not really. The sequence (genetic and protein) is what it is. The only "version" change that might be beneficial is fine-tuning the dosage (both in terms of mg of mRNA and possibly number of shots) for different ages.

Bear in mind the Moderna vaccine was specifically designed for the most "at risk" group there is: 65 and up. The main difference? it's 100mg of mRNA vs. 30 in Pfizer.

On the flip side of that, I would not be surprised at all if the side-effects in the young are higher in the Moderna group than the Pfizer group. I don't have data to support that yet, but there are enough anecdotal reports around for it to have crossed my mind more than once.

 

[bkp_duke]

Also, no idea if it’s possible that the epitopes targeted by cell-mediated immunity could be better targeted for Moderna than they are for Pfizer. I know the spike sequences are not identical, and epitopes targeted for cell-mediated immunity are different than those targeted by the neutralizing antibodies (I think?). That would show as increasing rates of hospitalization as neutralizing titers from humoral immunity wane…maybe?

If it is even theoretically possible (and not an immunologist so I have no idea), that would be bad, since it would mean consistent boosting would be required for Pfizer - while perhaps not for Moderna. In theory humoral immunity could wane for Moderna, and infections could rise, but if the cell-based response is better targeted for Moderna, that would keep hospitalization rates down regardless of increased infection rates because the second barrier is more effective.

Hopefully this is not the reason! Makes me wish I had waited for the Moderna mix-and-match!

I doubt it. mRNA sequence determines structure, and structure = epitopes presented to the immune system. The sequences are nearly identical, enough so that there is almost no appreciable difference in the 3D structure of the spike protein presented to the immune system. I think there are just more "chances" for those epitopes to be presented with Moderna because there is more mRNA, and likely more cells transcribing that mRNA, and therefore more Spike proteins available for the "APCs - Antigen Presenting Cells" of the the immune system to pick up.



Also, side note here - the REAL secret sauce of both Moderna and Pfizer is getting the cells of the body to "take up" their mRNA through the plasma membrane. The mRNA stuff itself is child's play. We've been doing that for nearly 50 years. The REAL breakthrough is whatever cocktail they are using that is able to get the cells to take up the mRNA is sufficient quantities to express the protein, without killing the cells. Anyone that's done "transfection" work appreciates this. The science is so good I have little doubt that whoever came up with these advanced transfection techniques is on the short list for a Nobel Prize.

For both Moderna and Pfizer, those transfection cocktails are proprietary as far as I know (but probably based upon some common research published within the past 10 or so years). Pfizer's cocktail may be better at uptake into the cells, and that's why they chose a lower dose. Or Moderna may be better, and that's why they have longer lasting antibody titers. Or they may be the same and it is just dose-dependent on the amount of mRNA. LOTS of unanswered questions that will fund research for at least a decade.

 

[madodel]

What is with the news media pushing the line that the booster recommendation is confusing people? It makes perfect sense to me. Maybe approval for all will come later but for now those most at risk. Why can't the media be supportive of this effort? They have to make up controversy no matter how they damage the mission. Just follow the science.

 

[bkp_duke]

What is with the news media pushing the line that the booster recommendation is confusing people? It makes perfect sense to me. Maybe approval for all will come later but for now those most at risk. Why can't the media be supportive of this effort? They have to make up controversy no matter how they damage the mission. Just follow the science.

Controversy = clicks = money.

No matter what "side" you fall on, they all have their $$$ puppet masters.

 

[dhanson865]

person I know that got Covid.

She got Pfizer in April/May (2 shots), got covid in Sept, died in Sept (within the last 12-24 hours).

would she have lived if she got Moderna instead, or if she got a booster of Pfizer (3rd shot), maybe, but she got what she got and that was the result.

Only the 2nd person I know that got covid and it was a breakthrough infection that ultimately was fatal.

 

[AlanSubie4Life]

Seems like Newsom got J&J and his young unvaccinated kids picked it up…so wonder whether he’ll be a breakthrough case.

They really need to address the J&J recipients - they’re highly vulnerable (especially the ones who are older/vulnerable/etc.).

“Get the first vaccine you’re offered,” they said…sigh…. Newsom taking an inferior vaccine, to encourage others to get vaccinated…taking one for the team.

(Shortcomings of Pfizer were only theoretical until more recently. But J&J was a known issue.)

 

[AlanSubie4Life]

I doubt it. mRNA sequence determines structure, and structure = epitopes presented to the immune system. The sequences are nearly identical, enough so that there is almost no appreciable difference in the 3D structure of the spike protein presented to the immune system.

Hopefully you’re right! If so, the booster of Pfizer should end up making it quite effective (as I understand it) since the delay somehow amplifies the response so even with the lower dose, it might be on par with Moderna then.

We’ll know in about 3 months (in Israel).

Hopefully Moderna holds up strongly against severe illness.

That’s the most troubling part of that CDC study - and it’s not entirely consistent with Pfizer studies done in other countries - severe illness (hospitalization) protection is substantially impacted. We know infection protection wanes for all the vaccines, but this much of a drop off of Pfizer for severe COVID-19 protection was somewhat unexpected (even from the trial data).

 

[msm859]

SIDE NOTE:
If we are really considering boosters, they should be re-formulated with the sequence of the Delta variant. I don't know what that means for FDA approval (would they have to be trialed like the originals, or could they be fast-tracked like what we do with Seasonal Influenza shots?).

Just my 0.02 of the subject of "well, if we are going to do boosters, might as well maximize their effectiveness".

Or should we be thinking that those who originally got the Pfizer should get the Moderna shot as their booster?

 

[alloverx]

Wasnt there a study in the UK about mixing vaccines?

 

[alloverx]

Trying to summarize the V-state-of-play

Background
-Moderna original jabs are stronger (100mg vs 30mg) than Pfizer
-After 120 days, Moderna protection is unchanged, Pfizer went down to 77% (historically still fantastic)

If previously had JJ, get a mRNA jab (single dose?)

If 65+, health-issues (high risk) or work-in-healthcare
If previous (double dose) vaccine was
Pfizer, get booster (same strength as original jabs?)
Moderna, wait for testing/review

if 12-17, get Pfizer
No booster

if 18-64, either vaccine OK
No booster

if male < 30, monitor for [after vaccine]
myocarditis (inflammation of the heart muscle)
pericarditis (inflammation of the lining around the heart)

 

[bkp_duke]

Or should we be thinking that those who originally got the Pfizer should get the Moderna shot as their booster?

Given how the recruitment of memory B cells to produce new antibodies works, it really shouldn't matter which they get for a booster. They just need the booster.

 

[AlanSubie4Life]

Given how the recruitment of memory B cells to produce new antibodies works, it really shouldn't matter which they get for a booster. They just need the booster.

I’m confused a bit. I just don’t understand exactly how this works.

My simplistic understanding is that since this is about hospitalization, it suggests an insufficient cell-mediated immune response generated by the first two doses of the vaccine.

At the same time, soon after two doses, the humoral response (antibody levels) was similar.

What specifically about the long delay before the third dose allows for a better cell-mediated response, bringing it on par with Moderna? And why is it sufficient to have a larger dose (Moderna) and get a good response after two doses?

What’s going on here that results in a highly protective immune response for Moderna? What specifically about the dose does this? - it doesn’t seem like more spike would necessarily do it.

My understanding is that this has little to do with serum antibody levels - those will always wane. Protection against severe disease has more to do with how well the body can rally T cells and the memory B cells, doesn’t it?

You allude to memory B cells above. Do you mean that the new dose will result in very high antibody levels (resulting in only a temporary boost in efficacy), or are you saying that somehow that cell-mediated response will be in better shape after the boost?

If it’s just the amount of mRNA that determines protection, that doesn’t make much sense - after the third dose it would be 90ug for Pfizer, compared to 200ug for Moderna (unless there are differing efficiencies in how well the cells take up and produce spike).

Based on your response I think this all must come down to the delay (affinity maturation) and not the dose, but I don’t really understand it.

 

[scottf200]

Or should we be thinking that those who originally got the Pfizer should get the Moderna shot as their booster?

Given how the recruitment of memory B cells to produce new antibodies works, it really shouldn't matter which they get for a booster. They just need the booster.

Thanks for the reminder. For others with fuzzy memories see the below.

Image below via this article: https://www.goodrx.com/blog/how-long-does-covid-19-immunity-last/

 

[msm859]

Given how the recruitment of memory B cells to produce new antibodies works, it really shouldn't matter which they get for a booster. They just need the booster.

And is part of the equation the time between shots? Pfizer being only 3 weeks. So today, if a 14 year old girl is going to get the vaccine - obviously Pfizer - should she get the second in 3 weeks or wait until 4 weeks after?

 

[EVNow]

if 18-64, either vaccine OK
No booster

Is the booster for this age group not needed or is it not useful ?

This is the one I was commenting on earlier. They should have recommended booster shots even if that would make a significant difference in immunity against symptomatic disease - not just base the decision on hospitalization.

Whatever happened to achieving herd immunity ?