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Effectiveness of Moderna booster shot and mix-and-match?

by warrenjordan1 min read26th Oct 20217 comments

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Covid-19
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I read that the FDA has approved the Moderna booster shot as well as mix-and-match shots. I have two doses of Moderna and inclined to take a booster as Pfizer's booster showed 95.6% effectiveness in their Phase 3 trial

Was wondering if any has substantial evidence or data on the Moderna booster shot and the mix-and-match shots? I'm eligible for it in a week and want to decide if I should get Moderna when it's available or mix with another booster. 

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Have a look at the presentation to the FDA's VRBPAC on 2021-Oct-15:

K Lyke, et al., "DMID 21-0012 - Heterologous Platform Boost Study Mix and Match", FDA VRBPAC 2021-Oct-15 Materials, retrieved 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:

  1. The comment on page 5: the study was "Not powered or designed to compare between the groups"
  2. 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.

1Weekend Editor1moYes, 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. 

2Weekend Editor1moThe 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 [https://www.someweekendreading.blog/covid-simpson/]. 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 [https://www.someweekendreading.blog/fda-covid-boosters-moderna/#the-israeli-case-for-boosters] 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 [https://www.someweekendreading.blog/fda-covid-boosters-moderna/#the-moderna-presentation] 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 symptomati

Excellent question, and I think a lot of us are wishing we had more data on this—unfortunately, there is very little data so far. But here's my take:

  1. If you had J & J for your first shot, I think there's enough evidence now to say it's probably (p = 0.7?) better to get Pfizer or Moderna for your booster.
  2. If you had Pfizer / Moderna for your first two shots, my instinct is that J & J might be the better choice, because there's an argument from microbiology that mixing types might produce a more robust response.
  3. If you had Pfizer / Moderna and want an mRNA shot for your booster, I don't think it'll make much difference which one you get: they're very similar.

There's an argument to be made that absent strong reasons to do otherwise, it's best to follow standard practice (in this case, to get the same brand of booster as the original shots) simply because you'll be in a larger, better-studied cohort.

A couple of sources, such as they are:

“But something has really become clear: The mixing really is most impactful when you have a DNA/adenovirus vaccine first followed by the mRNA vaccine,” Gandhi said. WaPo

The study’s researchers warned against using the findings to conclude that any one combination of vaccines was better. The study “was not powered or designed to compare between groups,” said Dr. Kirsten E. Lyke, a professor at the University of Maryland School of Medicine, who presented the data. NYTimes

“But something has really become clear: The mixing really is most impactful when you have a DNA/adenovirus vaccine first followed by the mRNA vaccine,” Gandhi said. WaPo

This is definitely true in terms of antibody fold induction: JnJ followed by either Pfizer or Moderna have the highest fold induction ratios.

However, they're starting from a lower baseline, since JnJ doesn't induce such high ab levels to begin with. (Though it might be better at training T cells and memory B cells, and have longer persistence? It's kind of frustratingly complicated, to... (read more)