Thread by @basilmd0

It has recently been suggested that vaccine boosters might “desensitize” an immune system to SARS-CoV-2, á la allergy shots.

That’s not how allergy shots work — I know because I prescribe them a lot.

I will elaborate for anyone interested. Let’s begin:

1/19

Say a person is allergic to ragweed. This means when they breathe in ragweed pollen, their body develops an immune reaction ➡️ allergy symptoms.

2/19

The ragweed pollen is an otherwise BENIGN object, i.e. it hasn’t directly caused damage to the body. The person’s immune response has. A non-allergic person could inhale the same pollen and have ZERO symptoms.

(I’ll explain why the point about damage is important later)

3/19

Allergy shots *desensitize* a person’s immune system. In this example, ragweed-containing shots will — over time — allow the allergic individual to breathe in ragweed pollen without having an immune reaction.

4/19

This treatment has been around for >100 years (cool, right?)

However, for shots to work you need to:
1️⃣ Start with a very low dose of allergen
2️⃣ Gradually increase dose w/ each shot until target level (usually takes 25-30 shots)
3️⃣ Not allow too much time b/w injections

5/19

In other words, you have to “teach” the immune system to tolerate something it would have previously reacted to.

Start basic. Slowly increase the difficulty. Give no fewer than one lesson a week.

6/19

By the end of the “semester”, if you will, the patient’s immune system has been trained such that its response to ragweed is indistinguishable from that of a non-allergic person.

7/19

Technical interlude (skip if you want)

Allergy shots cause:
⬇️ IgE to the allergen
⬆️ IgG to the allergen
⬆️ Number of Regulatory T cells specific to the allergen
🔄 No change in number of Helper T cells specific to the allergen

8/19

Now back to our famous SARS-CoV-2 mRNA vaccines.

Example, Pfizer.

🇺🇸 guidelines currently recommend:
An initial 30 mcg dose
3 weeks later, a second 30 mcg dose
6 months after that, a third 30 mcg dose

Moderna is ~ same except the 3rd dose is half strength

9/19

That’s it. 3 injections, and there are 6 months between # 2 and # 3. Not only that, in the only example of the dose being adjusted, it goes DOWN.

Does *that* sound like a desensitization protocol?
No. But there’s more!

10/19

Allergy shots work because the allergen is *inert*. In other words, ragweed pollen doesn’t intrinsically cause disease.

That’s why an immune system can learn to “tolerate” ragweed pollen just fine: it’s harmlessly floating around in tissue.

11/19

SARS-CoV-2 is quite obviously *not inert* and after it attaches to cells via the spike protein it causes extensive tissue damage and disease. Duh.

12/19

Damage to the body — even if microscopic — sends danger signals to the immune system.

An immune system doesn’t just decide to tolerate a protein if that protein unleashes hell every time it rolls up.

13/19

Each injection of spike protein mRNA generates local tissue damage (a manageable amount). That’s kinda the point — by creating a disturbance, your immune cells get attracted to the injection site and learn to flag the spike as a troublemaker. 🚩

14/19

Here’s the kicker: we HAVE real life examples of vaccine desensitization to study from! For example, the influenza vaccine.

Patients allergic to flu vax can achieve tolerance *to the vaccine* using a similar gradual build-up process to what we talked about w/ ragweed.

15/19

At the end, those vaccine-allergic patients are partially protected BY THE VACCINE against flu virus. If immune tolerance to the 🦠 occurred, you’d expect those individuals to become super-vulnerable to flu infection.

But they aren’t.

16/19

One last technical point: I mentioned that the T cells specific to an allergen don’t go away with allergy shots, they just get “reeled in” by an expanded population of regulatory T cells.

The notion that T cells might get “deleted” by repeated shots is also false.

17/19

Let me be clear: I’m not advocating endless boosters. For all we know they may cause too many unwelcome side effects past a certain point, or just stop being helpful.

Philosophically, I’m in favor of the fewest doses necessary, no matter the intervention or disease.

18/19

But I hope this 🧵 has illustrated why the concern around “desensitization” and “immune tolerance” from multiple mRNA vaccine injections is completely unfounded.

The comparison between boosters and allergy shots simply doesn’t hold.

19/19 END

#MedTwitter #allergy #immunology