(If you’re curious about the how the whole meeting went down, I wrote a little summary.)
Slide 22 (page 23, because the FDA tacks on a header page) should help. It’s a 3x3 array of the 3 original vaccines x 3 possible booster vaccines. It shows the factor by which antibody levels are boosted by each primer/booster combination (geometric mean titer fold induction).
For your case of a Moderna primer, the middle column is the one to look at: Moderna booster gave 10x boost, JnJ booster gave 6.2x, and Pfizer booster gave 11x. Given the error bars on that slide, Moderna and Pfizer are more or less indistinguishable (10x vs 11x), but both are likely better than JnJ.
In terms of absolute ab levels (the number shown in blue), a Moderna booster is probably a touch higher than Pfizer (3727 vs 2801), though I haven’t used the error bars to calculate the statistical significance of that. Both are pretty good.
For me, the bottom line is that it looks like either Pfizer or Moderna are fine for somebody who’s already gotten 2 doses of Moderna. The important thing is to get the booster if you need it; the choice of Pfizer or Moderna is over-optimization.
Excellent data: thank you! Two things to keep in mind:
The comment on page 5: the study was “Not powered or designed to compare between the groups”
They’re only looking at antibody levels (because those are relatively easy to measure), but there’s a good argument that some of the differences between strategies will involve activation of B cells & T cells.
The comment on study power is why I was pretty surprised at the FDA and CDC approvals, based on this study which itself says it’s underpowered. I think they were mostly motivated by the safety results that boosters were at least as safe as the primers. So if it might do some good and probably does no harm, they can get to an EUA from there.
This is not the way they usually behave, but then again, these are not usual times.
Was wondering if you knew of any sources of how efficacy wanes over time (or persists) for two-doses of Moderna? I’m not actually sure if I do need a booster since I have no clue what baseline I’m working with.
The evidence on vaccine efficacy waning is somewhat confusing to me!
On the one hand: Some of the initial data on waning from Israel (using Pfizer) was hopelessly confounded with age, leading to a huge Simpson’s paradox effect. Once you (a) figure out the Bayes error (they calculated Pr(vax | hospitalization) when they really wanted Pr(hospitalization | vax)), (b) properly stratify by age, and (c) calculate confidence limits on vaccine efficacy, the effect goes away.
On the gripping hand: Both of those show the onset of “waning” coincident with the onset of the Delta variant, i.e., last summer. So was it really waning, or was it Delta? I can’t tell.
They show a waning effect with respect to initial infection, but continued robust protection against hospitalization (still 85-90%). That could be normal:
Antibodies do decrease with time. You’re not carrying huge blood levels of antibodies for every virus you’ve ever encountered thus far in your life.
But T-cells and memory B-cells are still there. When an antigen from a previous infection is presented to the relevant memory B-cells, they trigger production of antibodies which then stop the infection. That way you can be technically infected for a couple days while that happens, but be asymptomatic or mildly symptomatic, and quickly clear the infection.
So it might be that we’re just seeing antibodies fade, but which rapidly come back upon re-challenge with the virus.
On the (unnamed) fourth hand: I looked at a recent study by Townsend et al. at the Yale School of Public Health that analyzed 6 coronaviruses known to infect humans and related to SARS-CoV2, predicting that there’s a 50% chance of reinfection at 18 months. So maybe periodic boosters will be required because of waning immunity?
So… “I notice that I am confused.” But since all this is happening frighteningly quickly and we’re just learning how it all works, confusion is the normal state of affairs at the leading edge of science. Thus my confusion might be normal.
Or maybe I’m just plain old confused and need somebody to straighten me out. That’s also regrettably normal, at least for me.
Until then, it seems that 2 things are worth remembering:
Boosters do seem to work in terms of boosting ab levels, and don’t seem to cause any worse side effects than the first doses.
If there is waning, boosters are an effective strategy; if there is no waning, then because of the non-terrible side-effects, boosters are a safe strategy, i.e., unlikely to do much harm.
So I got a booster, and my spouse gets one in a few days when eligible.
Have a look at the presentation to the FDA’s VRBPAC on 2021-Oct-15:
(If you’re curious about the how the whole meeting went down, I wrote a little summary.)
Slide 22 (page 23, because the FDA tacks on a header page) should help. It’s a 3x3 array of the 3 original vaccines x 3 possible booster vaccines. It shows the factor by which antibody levels are boosted by each primer/booster combination (geometric mean titer fold induction).
For your case of a Moderna primer, the middle column is the one to look at: Moderna booster gave 10x boost, JnJ booster gave 6.2x, and Pfizer booster gave 11x. Given the error bars on that slide, Moderna and Pfizer are more or less indistinguishable (10x vs 11x), but both are likely better than JnJ.
In terms of absolute ab levels (the number shown in blue), a Moderna booster is probably a touch higher than Pfizer (3727 vs 2801), though I haven’t used the error bars to calculate the statistical significance of that. Both are pretty good.
For me, the bottom line is that it looks like either Pfizer or Moderna are fine for somebody who’s already gotten 2 doses of Moderna. The important thing is to get the booster if you need it; the choice of Pfizer or Moderna is over-optimization.
Excellent data: thank you! Two things to keep in mind:
The comment on page 5: the study was “Not powered or designed to compare between the groups”
They’re only looking at antibody levels (because those are relatively easy to measure), but there’s a good argument that some of the differences between strategies will involve activation of B cells & T cells.
See also the limitations on page 33.
Yes, absolutely.
The comment on study power is why I was pretty surprised at the FDA and CDC approvals, based on this study which itself says it’s underpowered. I think they were mostly motivated by the safety results that boosters were at least as safe as the primers. So if it might do some good and probably does no harm, they can get to an EUA from there.
This is not the way they usually behave, but then again, these are not usual times.
This is great, thanks!
Was wondering if you knew of any sources of how efficacy wanes over time (or persists) for two-doses of Moderna? I’m not actually sure if I do need a booster since I have no clue what baseline I’m working with.
The evidence on vaccine efficacy waning is somewhat confusing to me!
On the one hand: Some of the initial data on waning from Israel (using Pfizer) was hopelessly confounded with age, leading to a huge Simpson’s paradox effect. Once you (a) figure out the Bayes error (they calculated Pr(vax | hospitalization) when they really wanted Pr(hospitalization | vax)), (b) properly stratify by age, and (c) calculate confidence limits on vaccine efficacy, the effect goes away.
On the other hand: Later Israeli data presented at the Moderna booster hearing cleaned that up and showed there was a waning effect. Moderna did something similar with their vaccine, comparing the people in the treatment arm of their clinical trial vs those in the control arm who got the vaccine 6 months later when it read out, showing a waning effect between those 2 carefully matched groups with known distributions of age, race, gender, etc.
On the gripping hand: Both of those show the onset of “waning” coincident with the onset of the Delta variant, i.e., last summer. So was it really waning, or was it Delta? I can’t tell.
They show a waning effect with respect to initial infection, but continued robust protection against hospitalization (still 85-90%). That could be normal:
Antibodies do decrease with time. You’re not carrying huge blood levels of antibodies for every virus you’ve ever encountered thus far in your life.
But T-cells and memory B-cells are still there. When an antigen from a previous infection is presented to the relevant memory B-cells, they trigger production of antibodies which then stop the infection. That way you can be technically infected for a couple days while that happens, but be asymptomatic or mildly symptomatic, and quickly clear the infection.
So it might be that we’re just seeing antibodies fade, but which rapidly come back upon re-challenge with the virus.
On the (unnamed) fourth hand: I looked at a recent study by Townsend et al. at the Yale School of Public Health that analyzed 6 coronaviruses known to infect humans and related to SARS-CoV2, predicting that there’s a 50% chance of reinfection at 18 months. So maybe periodic boosters will be required because of waning immunity?
So… “I notice that I am confused.” But since all this is happening frighteningly quickly and we’re just learning how it all works, confusion is the normal state of affairs at the leading edge of science. Thus my confusion might be normal.
Or maybe I’m just plain old confused and need somebody to straighten me out. That’s also regrettably normal, at least for me.
Until then, it seems that 2 things are worth remembering:
Boosters do seem to work in terms of boosting ab levels, and don’t seem to cause any worse side effects than the first doses.
If there is waning, boosters are an effective strategy; if there is no waning, then because of the non-terrible side-effects, boosters are a safe strategy, i.e., unlikely to do much harm.
So I got a booster, and my spouse gets one in a few days when eligible.