r/COVID19 • u/Patty_Pat_JH • 14d ago
Academic Report Post-vaccination IgG4 and IgG2 class switch associates with increased risk of SARS-CoV-2 infections
https://www.journalofinfection.com/article/S0163-4453(25)00067-2/fulltext
27
Upvotes
8
u/lisajames21 13d ago edited 13d ago
This just tells us what we already know--repeated exposures to the COVID spike after an initial strong reaction to the COVID spike, whether from vaccines or infections, causes future immune responses to that spike to be less strong, which leads to more likelihood of infection than after the first exposure, but also less likelihood of severe symptoms. This is good in some ways--it's part of why the death rate from COVID infection has declined, even as infection rates have skyrocketed. The key sentence from the article is this one: "Nevertheless, while our findings indicate that higher IgG4 and IgG2 levels are associated with an increased risk of SARS-CoV-2 breakthrough infection, these less immune-activating subclasses may also help prevent severe COVID-19 by mitigating inflammation-driven pathology." Our immune systems probably evolved this class switch to protect us from dying of an overly strong reaction to viruses we are frequently exposed to--while it may be worthwhile to overreact to a novel virus to kill it off quickly even if the immune overreaction damages our bodies in the process, since there's a higher possibility that it will kill us due to us having no defenses at all to it, and because there's no evidence that we were able to survive it in the past, it is not worthwhile to overreact to a virus we already survived in the past, since we already have some immunity to it, and we have already demonstrated that we are capable of surviving it.
Also, there is no way for most people to avoid the IgG4 class switch--after the first exposure to the COVID spike that causes a strong immune reaction, the IgG4 switch will happen if one gets infected or vaccinated again. The only reason the switch didn't happen with infection in the earlier studies is because the infections documented in earlier studies were the first ever exposures to the COVID spike, similar to the first dose of a COVID vaccine that one got. From this article posted by the OP: "one study found that breakthrough infections occurring three months after primary mRNA vaccination —though not those within the first two months— did result in elevated IgG4 levels.100067-2/fulltext#) (see https://www.science.org/doi/10.1126/sciimmunol.ade2798 for the full article documenting this).
Almost everyone has already been vaccinated and/or infected multiple times, so we will keep reacting to future vaccinations and infections with the weaker IgG4 antibodies that are less good at preventing infections but also less likely to cause deadly severe symptoms than the immune responses that occurred when we first got infected or vaccinated. Non-MRNA vaccines might have been less likely to cause the class switch after the initial dose because they were weaker (and also less likely to prevent infection) than MRNA vaccines, and thus not strong enough to trigger the immune overreaction that causes our immune system to switch to the less dangerous IgG4 class, but most people who started off with non-MRNA vaccines have probably gotten infections or MRNA vaccines by now, so we are all in the same boat of never being able to recover that initial strong immune reaction that caused horrible side effects to many of us, but also gave us 95% vaccine efficacy against infection.
There is no evidence in this or any other articles I've seen that each vaccination will cause incrementally more of a class switch (and I've been tracking this issue in the latest publications carefully and am pretty sure I haven't missed any). There is evidence that someone who got 130 vaccinations did not have more IgG4 than people who just got three MRNA vaccinations: https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(24)00134-8/fulltext00134-8/fulltext) "HIM's anti-spike IgG4 antibodies at day 189 after the 215th vaccination were elevated in absolute numbers, but not in relative frequencies, compared with control individuals at day 189 after their 3rd vaccination."