IMO, this illustrates a major problem with the current approach to Covid vaccine research.<p>With most vaccines on the market, the effect of vaccination according to the recommended schedule is tested for real: actual disease outcomes are studied and the vaccine schedule is determined accordingly. For example, people who get both measles vaccine doses largely don’t get measles (and largely is quantified). People who get two doses of the chickenpox vaccine don’t get chickenpox [0].<p>With the Covid vaccines, for some reason public health authorities are okay with flying blind. The effect of, say, bivalent boosters on their recipients’ blood neutralizing viruses and virus-like imitation viruses are studied in the lab (but even the studies of this effect by the vaccine makers are barely public and seem to consist mostly of press releases). Studies on actual infections rates seem to be almost completely absent.<p>And now we have this study, which at least gives a plausible mechanism by which repeated mRNA vaccination could fail to improve actual immunity or maybe even reduce it.<p>What we need is a real study of whether vaccine recipients on different schedules <i>get sick</i> and <i>how sick</i>. And these need to be well designed, ongoing, and public.<p>For what it’s worth, IgG4 production is observed in allergy patients receiving immunotherapy, which consists essentially of very frequent repeated vaccination against allergens.<p>[0] The chickenpox vaccine is incredibly effective against chickenpox — it makes any of the Covid vaccines look pathetic. But, to be fair, the effect of chickenpox vaccination on shingles seems to only slowly coming in to focus by real studies. But to give the FDA credit, figuring this out takes multi-decade studies.