For years, one question has lingered in the back of my mind—quietly but persistently.
Why is COVID still spreading in places where almost everyone is vaccinated?
We were told early on that high vaccine uptake would reduce circulation of the virus. And yet, countries like Portugal, with over 95% vaccination rates, continued to report widespread infections. The usual answer? Variants. The virus is evolving, they said—so we need updated boosters. But if you understand even the basics of immunology, this explanation starts to crumble under scrutiny.
A healthy immune system doesn’t rely on matching every variant exactly. It creates broad, durable responses—targeting multiple parts of the virus, not just one. So why would small changes in the spike protein render immune memory ineffective? The uncomfortable possibility is this: our immune response itself has changed. That’s what I want to unpack here.
The IgG4 Shift: An Immunological Red Flag
There’s a paper I’ve been following closely. It came out earlier this year but flew under the radar. Its title says it all:
“Post-vaccination IgG4 and IgG2 class switch associates with increased risk of SARS-CoV-2 infection.”
In simple terms, it confirms what many of us had suspected: after repeated mRNA COVID-19 boosters, the immune system starts making more of a specific antibody type—IgG4—that's not built to fight off viruses.
Let me explain.
The immune system uses different types of antibodies (think of them like immune missiles). The heavy-hitters—IgG1 and IgG3—are pro-inflammatory, neutralizing, and great at clearing infections. IgG4, on the other hand, is a tolerance antibody. It shows up when the immune system decides to stop reacting, like during allergen immunotherapy or chronic exposure to harmless antigens.
But here’s the twist: after the third mRNA dose, IgG4 levels skyrocketed—by more than 38-fold. That's a 4,000% increase. And in some individuals, up to 45% of their spike antibodies were IgG4. Compare that to just 1% in people who had natural infection. It’s a profound and unexpected shift.
What’s the Consequence of Too Much IgG4?
The study found that higher levels of IgG4—and a higher ratio of “tolerant” to “cytophilic” antibodies—were associated with up to an 80% increased risk of breakthrough infection. That’s not a fringe observation—it’s statistically robust.
Why does this happen? One theory is that mRNA vaccines, especially when given repeatedly, overstimulate the immune system in a narrow direction—constantly exposing it to the same spike protein in a way that mimics chronic exposure rather than acute infection. Over time, the immune system may "tune down" its response.
And here’s where it gets complicated.
Thursday 10th July, 2025 at 7PM UK time
Could This Be Protective—or Problematic?
Some may argue that IgG4 is beneficial. After all, in severe COVID-19, the real danger was often the immune overreaction—the so-called cytokine storm—not the virus itself. From that perspective, a shift to tolerance might actually protect against damaging inflammation.
But this comes with a big catch: you have to stay on the booster treadmill. If your immune system has downshifted into tolerance, but viral exposure continues and IgG4 levels decline, could you become vulnerable again—not just to infection but to a misfired immune response?
That’s the worry.
Why This Matters Now
This isn’t a critique of vaccines per se. Vaccines remain one of the most important tools we have. But the mRNA platform is unique, and it behaves differently than traditional vaccines. We now have clear evidence that it alters antibody class switching in a way that may not be entirely beneficial—at least, not after repeated doses.
And this isn’t just about COVID anymore. mRNA vaccines are being developed for RSV, flu, even cancer. If IgG4 class switching is an unrecognized consequence, we need to understand it before applying this platform broadly.
This kind of immunological pattern doesn’t show up overnight. The Spanish cohort study that uncovered this began in 2020—tracking immune responses over time. You can’t just recreate that kind of data. That’s why I believe this study is so important, and why it can’t be ignored.
Where Do We Go From Here?
The solution isn’t to panic or abandon vaccines. The solution is to think carefully and adjust our strategies:
Should we limit the number of mRNA boosters?
Can we alternate with other vaccine platforms to avoid immune tolerance?
Should we measure IgG subclasses in at-risk populations?
Is it time to stop Covid vaccines completely?
These are questions policymakers and scientists should be asking. Until they do, I’ll continue raising them—because the science matters.
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