[amluto]

I’m not convinced that mRNA vaccines as they currently exist are well suited for repeated boosting against the same virus. See, for example:

https://www.science.org/doi/10.1126/sciimmunol.adg7327

And also the quite disappointing efficacy that the CDC reports for repeated Covid boosters.

[tptacek]

Is the Covid issue mRNA, though, or is it how much of a moving target they were trying to hit with the bivalent booster?

[bluGill]

The flu mutates more readily than COVID. With the sudden spread of COVID around the world we saw a few mutations, but the flu would mutate a lot more given the same spread. Most of us have some flu immunity though and that tends to limit spread, so it seems there are less mutations.

[XorNot]

Right but that varies from virus to virus - the goal of a universal flu vaccine is to hit a well-conserved region of the virus which doesn't mutate much. Our inability to do it so far doesn't necessarily imply it's impossible.

Whereas most current COVID vaccines target the spike, and disappointingly the spike is a lot more malleable then hoped.

[peteradio]

> Our inability to do it so far doesn't necessarily imply it's impossible.

It's a fairly solid indicator though that it must be tricky or that the body is making some tradeoff.

[XorNot]

Or just that we can't stabilize/synthesize the protein usefully in a vaccine with existing techniques.

One of the big deals of mRNA is that because you get the proteins made in-vivo (in the body), you inherit all the body's machinery to do this naturally - after all, viral replication requires using that exact same machinery in order to replicate up the viral proteins in the first place.

[amluto]

The bivalent booster was pretty much on target in late 2022 and the beginning of 2023, and if it had been anywhere near as effective as the original two-dose series, I would have expected rather better results than this:

https://www.cdc.gov/mmwr/volumes/71/wr/pdfs/mm7148e1-H.pdf Table 3

These are somewhat less unimpressive (IMO) numbers here:

https://www.cdc.gov/mmwr/volumes/72/wr/pdfs/mm7205e1-H.pdf

https://www.nejm.org/doi/full/10.1056/NEJMc2215471

I don’t think one can draw a conclusion as to what exactly is wrong. IMO it’s too bad that Novavax flubbed their vaccine rollout so badly — it would have given valuable comparison data.

[revelio]

Conclusions are possible, the causes are known. You aren't going to get it from the CDC though.

The problem is the first round of vaccines caused immune fixation. The boosters failed because the body can't tell the difference between such similar proteins and made antibodies for the 2019 spike variant instead of the one the booster was targeting, thinking it already knew what to do.

This was covered up during approvals by redefining the success criteria as elevated levels of antibodies to "spike protein" without being specific about which one, and then ignoring actual effectiveness numbers (which were zero or negative).