“As we age, we accumulate an “antigenic burden,” the sum of all the
antigenic stresses (both internal and external) that we unavoidably
encounter throughout life, which causes the progressive activation of
macrophages and other immune-cell types. This low-level chronic
activation leads to the continuous production of inflammatory factors
such as cytokines and chemokines, which raises basal levels of these
factors throughout the body”
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Probably less of an antigenic burden than a high viral load of the disease itself. Inflammation from the illness can be really nasty.
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Myocarditis from virus >>> myocarditis from vaccines. And we already know annual flu shot is a huge prevention factor for heart disease. The known effect size of taking influenza shot every single year is far greater than the unproven effect size you are hypothesizing.
Ever had sepsis/SIRS before? Sucks. Long COVID sucks too - wonder how the disability insurers are going to handle it. Older adults are less likely to get long COVID actually.
I am enrolled in a bunch of vaccine trials so I’m probably biased. The only caveat is I don’t mindlessly take experimental vaccines without fully understanding the microbio and immunology (I happen to know a lot of infectious disease physicians and did infectious disease research before with a NIH/NIAID grant). I never got covid so far (unless it was asymptomatic) with rapa + trials - been a lucky 2/3 roll for the interventions group so I get the variant specific one before it hits the market. Trial guy said I had amazing antibody level (hard to say with T cell immunity tho!).
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I also got a Tdap vaccine for the cross protection against Covid.
Also got pneumovax and shingles vaccines.
I’m the antithesis of an anti vaxer.
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Yeah, but like, if you already have been boosted and am wondering whether or not to get boosted again with a booster that ISN’T for BA.5, this is relevant.
"And there is concern that if people get the same shot too many times it could be counter-productive — by kind of training their immune systems to only try to fight off the original strain instead of protecting against new variants. Although this remains a theoretical risk, some say the evidence that it might be real is growing.
“There’s this phenomenon of imprinting also known as original antigenic sin where if you continue to give doses of the same vaccine you could in a sense trap the immune system of wanting to respond to the original virus and not adapting as well to future variants,” says Dr. Céline Gounder, an infectious disease specialist and a fellow at Kaiser Family Foundation."
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Empirically, large multicenter prospective trials on influenza vaccine vs CVD risk and death have very strong evidence that shows flu shots work, even if you are “imprinted” with the flu vaccine as a child. The effect size is massive and hard to ignore for any scientist. I suspect to support your theory - you’d need quite some extraordinary evidence.
COVID vaccine mixing and Beta strain vaccine outcomes don’t seem to have any signs indicating the supposed empirical support that theory proponents would expect. So it really makes no sense so far.
Not to mention, I got the experimental Omicron variant COVID vaccine and have living proof that it is fine for me.
Maybe for older people could be an issue, but it doesn’t seem to be so far based on trial results. Maybe we might see something with several years or decades of different variants.
I would look for stronger empiric support for that theory first in terms of direct death-related outcomes since there’s quite a bit going against it. We have such a large sample size showing no death.
It’s pretty hard to argue with death vs no death with large numbers in terms of precise evidence to support a theory.
from @Olafurpall
You’re right in that the ravages of aging wear out the immune system, but you’re missing the fact that encounter and responses to vaccines and infections is one of those ravages. While you’re correct in that exposure to pathogens in youth leads to development of immunity that is beneficial at older ages, you’re assuming that the body can get exposed to and form immunity against unlimited number of pathogens without any negative effects. This assumption is wrong due to something called immunological space.
Every time your immune system encounters an “enemy”, be it from a vaccine or an infection, and it responds appropriately, the body will develop immunity to that enemy. It does this by training memory B-cells and T-cells that recognice the antibodies on the enemy so if you get exposed to it in the future your immune system will respond fast and destroy it before you get significantly ill. This is all good, except that each time your body does this, the new memory cells take up immunological space and leave less left for novel future infections.
Here is an analogy to explain this better. Imagine you live in a city with 1000 police officers whose sole job is to catch terrorists. Whenever some terrorist arrives in the city, eventually some police officer catches him and neutralizes him. And when he does so he remembers what he looks like and also hands 9 other police officers a picture of how the terrorist looks like. Now we have 10 officers that know how this terrorist looks like and they now get orders to only look out for this terrorist. If a new terrorist comes in town, the 10 officers will not notice, because they have been dedicated to recognize this single one and be blind to anyone else. This leaves only 990 officers left to recognize new terrorists. Every time a new terrorist arrives, ten new officers get dedicated to recognize that one and the number of remaining officers decreases. In many years you might end up having 500 officers dedicated to various terrorists that have entered the city leaving you with only 500 left to recognize new ones. This makes the police in the city half as efficient at recognizing new terrorists than in the beginning when you had 1000 officers free to recognize new ones because the total space only allows for 1000 officers in the city. The immune system is a bit similar in that there is only room for so many B- and T-cells in the body, hence the term immunological space. Some of them are naive and ready to recognize new pathogens. Every time you get exposed to a pathogen or a vaccine, a number of B- and T-cells gets dedicated to that pathogen and the number of naive B- and T-cells decreases. This is one reason why immunity declines with age and why old people don’t respond as well to vaccines as young people. They don’t have as many B- and T cells to recognize new enemies because so many of them have been turned into memory cells that are dedicated to recognize only some old enemy.
This is how every time you get exposed to vaccines or catch an infection your immune system gets older in at least one aspect, that is, the immunological space decreases. Granted this won’t be a problem for average people until they get quite old and their immunological space gets pretty full, but if you’re thinking about longevity, this is definitely a factor worth considering. Note that, in line with this, B-cell depletion therapy (to remove memory B-cells and make more space for naive B-cells) has been proposed as a method to partially rejuvenate immunity.
The gradual filling up of immunological space in response to pathogen exposure is an example of antagonistic pletropy. It’s beneficial for early life fitness but starts getting harmful later in life. Probably the optimal balance between naive and memory B- and T-cells is reached sometime in early middle age and optimally one would maintain a similar ratio later in life.
Olafur
mRNA COVID vaccines are way more taxing to the immune system than flu shots. I keep getting my COVID boosters, but I know most people don’t
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There are some people who get worse long COVID from too many COVID shots + COVID infections. I plugged it into G5T (I believe it systematically underestimates the risk a bit):
Short answer (in one breath):
For most people a few boosters lower the odds of long COVID, but in a small, unlucky subset piling on shots at short intervals can rev-up a quirky immune system—think “over-caffeinated T cells”—and that extra buzz can keep symptoms smoldering rather than snuffing them out.
1. What the data actually show
| Snapshot | What most studies report | Minority signal |
|---|---|---|
| Systematic reviews & national cohorts | 1-2 boosters cut risk of developing long COVID by ~15–40 % and sometimes improve existing symptoms | Case-series & patient surveys describe flares lasting days-weeks after a booster in <10 % of long-COVID patients |
| Big-data VA analysis (2025) | Overall protection against severe disease persists; long-COVID risk tracks more with reinfections than with extra doses | Sub-analyses hint that people taking ≥4 mRNA doses within 18 months have slightly higher odds of persistent fatigue and dysautonomia |
So: helpful for most, bothersome for some.
2. Mechanisms that
might
turn “protective” into “provocative”
| Suspected pathway | How it could back-fire | Key evidence |
|---|---|---|
| Immune imprinting (“original antigenic sin”) | Repeatedly teaching B cells the old Wuhan-style spike may lock in narrow antibodies that don’t fully neutralize newer variants. Low-level viral persistence ⇒ chronic inflammation. | Reviews & lab studies show blunted de-novo responses after ≥3 ancestral-spike doses |
| Persistent spike / mRNA in tissue | Every booster re-introduces spike‐encoding mRNA. In a subset, spike lingers (∼30–700 days!) → endothelial irritation, micro-clots, brain-border inflammation. | Human autopsy & plasma studies detecting long-lived mRNA and spike protein |
| Mast-cell activation & dysautonomia | Vaccination is a big innate-immune jolt; in people with mast-cell priming (common in long COVID) it can trigger histamine storms, POTS-style symptoms. | MCAS-long-COVID overlap and post-booster MCAS case report |
| Autoimmunity “over-polishing” | Frequent antigen exposure may stoke self-reactive B/T cells; small uptick in SLE seen after multiple boosters. | Autoimmune surveillance studies |
| IgG4 class-switching | Extra doses shift antibodies toward tolerance-style IgG4; usually harmless, but in theory could blunt viral clearance in some and perpetuate antigen drip. | Clarified in German IgG4 study debunking extreme claims |
(None of these are slam-dunk proof—think “working theories,” not courtroom evidence.)
3. Why “too many” matters
- Dose density – Immune memory needs space to mature. Boostering every 2–3 months can freeze antibodies mid-evolution.
- Antigen sameness – Four shots of almost identical spike ≠ four lessons; it’s more like rereading the same textbook.
- Host susceptibility – Pre-existing long COVID, MCAS, auto-antibodies, or certain HLA types seem to amplify the risk of symptom flares.
4. Tips for people already battling long COVID
| Strategy | Rationale | Practical take-away |
|---|---|---|
| Stretch the interval | Let B-cell affinity mature & lower innate-immune burden. | Current CDC advice is “annual” for most; many long-COVID clinics suggest ≥6 months unless high-risk exposure looms. |
| Switch platforms | Protein-based Novavax or updated variant vaccines may avoid imprinting + reduce mast-cell triggers. | Ask about non-mRNA boosters—Novavax got US EUA, full approval pending |
| Antihistamine / mast-cell protocol | Dampen flare risk. | H1/H2 blockers or cromolyn starting 24 h pre-shot (under physician guidance). |
| Check antibody titers | Avoid “over-boosting” when titers already sky-high. | Not yet standard of care, but some specialists track spike-IgG + neutralization to time boosters. |
| Parallel antivirals | If suspecting hidden viral reservoir, short Paxlovid course + booster studied (results mixed) | Still experimental—discuss in clinical-trial setting. |
5. Bottom line
Vaccines remain the MVP against severe COVID, and, in aggregate, they lower long-COVID risk.
Yet biology loves exceptions. In a subset with immune quirks, stacking boosters too fast or too often can nudge an already dysregulated immune orchestra further off key, prolonging or worsening symptoms. Working with an experienced clinician—spacing doses, considering heterologous platforms, calming mast cells, and tackling lingering virus or autoimmunity—offers the best shot (pun intended) at beating the odds.
(And remember: “the dose makes the poison”—even for spike protein.)