Yep, I don't really understand affinity maturation processes exactly, but apparently that's what it is.
So I don't quite follow statements like this:
I don't get this from an immunologist. I mean, it's not really true in any sense - antibodies wane and another challenge will raise the levels again, no the immune response is really never "plateaued." In addition, with the booster, improving breadth and quality (in some way I don't understand). I definitely would like an immunologist to explain in pedantic detail. I would imagine the breadth and quality (but not quantity as described above) of the antibodies DOES reach a limit at some point in the series. Whether that's after 3 or 4, no idea. Three doses was still improving, so might be worth a shot at number four (should be eligible in a couple months though not clear what will be allowed after 6 months and whether a fourth dose will be permitted) .
Not true, I would like to know exactly which immunologist said that, because that is patently false information.
Repeated exposure to the SAME epitopes (i.e. the same vaccine with the exact same genetic sequence) will plateau a response. Sure, a 4th dose of the same vaccine might get you levels moderately higher than the third dose (comparing peak to peak), but they WILL be diminishing returns that asymptote, and a vaccine that does this FAR INFERIOR to a booster from a vaccine with a different genetic sequence and different epitopes on the protein. Boosters that broaden the immune response provide better coverage overall than those that keep selecting for the same antibodies.
There are feedback loops in just about everything in the human body, including antibody production. The natural way the human immune system gets around this and to enhance the immune response to a pathogen is to produce antibodies to as many epitopes on as many proteins as possible (i.e. a polyclonal response). It helps reduce "immune escape" by tossing a wider blanket on the infection. With that wider blanket, when things like Omicron come along that have substantial mutations, there are more memory B cells with proper antibodies that can response and ramp back up, vs. a ton of B-cells with the wrong antibody epitopes that won't respond at all.
Pushing the same booster over and over selects memory B-Cells which produce nearly a monoclonal response (not quite, but definitely selecting for that).
All else equal, polyclonal responses are always GREATER THAN monoclonal responses.
Additionally, the goal of vaccines, LONG TERM, should be to develop a proper memory B cell repertoire. There is a myopic focus on antibody levels right now, but in all vaccines antibody levels wane over time in favor of keeping a core group of memory B cells around that can ramp up quickly to an infection and re-produce the antibodies. You don't go get MMR, etc. boosters as adults, because you have memory B cells which can react to an infection and spool up antibody production.
Related, but not directly in response to the above - given how quickly Omicron is spreading, I would bet the R-value is substantially above Delta, which was substantially above the Wuhan original. Masks are going to provide diminishing levels of protection as the R-value increases. So this "experiment" is going to run it's course one way or another and we'll have the data to answer all these questions. We will see infections in the vaccinated, even if they wear masks, and we will know how well the current vaccines protect after 2 doses, 3 doses, etc. We will know how well native immunity from prior infection protects.
My "educated guess": this is a coronavirus, it is COMMON for humans to get re-infected with coronaviruses long before SARS-CoV-2 came into being. We get it, fight the infection off (first exposures are always elementary age children), and then we get them again later in life. Literally, they are common cold viruses (one of half a dozen species), and they have evolved long before SARS-CoV-2 so that they have the ability to keep re-infecting people. Fortunately, that means the evolutionary trajectory is to become something less deadly and "endemic". We will watch that play out over the coming years.
