Rapamycin, Infections and Vaccines
Rapamycin's first job was to stop transplant patients rejecting their new organs, which it does by suppressing the immune system. That history sits behind every conversation about taking it for longevity, and it produces two opposite errors: the person who assumes it will leave them defenceless, and the person who has read one paper about the flu vaccine and assumes it will make them bulletproof.
Neither is right. This page sets out what the evidence shows about rapamycin and immunity, and the practical rules we apply.
Two very different exposures
At transplant doses — daily, continuous, often combined with other immunosuppressants — rapamycin reliably increases infections, slows wound healing and raises the risk of some cancers. That is what the label describes, and it is real.
Longevity use is a different exposure: intermittent rather than continuous, at a fraction of the transplant level, and alone. The difference is not cosmetic. mTOR — the enzyme rapamycin inhibits — exists in two complexes, and continuous high exposure suppresses both, while intermittent exposure is thought to act mainly on the first. The immune consequences of the two patterns are not the same, and the transplant literature does not simply transfer.
We do not describe the longevity pattern in terms of amounts or schedules, here or anywhere on this site. What we can describe is what has been observed in people using it.
The flu-vaccine paradox
The best-known finding in this area came from a 2014 trial in Science Translational Medicine. Healthy adults over 65 took an mTOR inhibitor closely related to rapamycin for six weeks before a flu vaccine. Those on the drug mounted a stronger antibody response to the vaccine than those on placebo — about 20% higher — and showed fewer of the exhausted T cells that accumulate with age. A follow-up trial in 2018 found fewer reported infections over the following year.
That is the paradox: a drug that suppresses immunity at one exposure appeared to rejuvenate it at another. The mechanism is thought to involve clearing the senescent, over-activated state that aging immune cells fall into — turning the volume down so the signal can be heard.
Two cautions. The drug in those trials was everolimus, not rapamycin itself, though the mechanism is shared. And a later, larger trial of a related compound for respiratory infections did not meet its primary endpoint, which is a reminder that a striking early result is a hypothesis, not a settled fact.
What longevity users actually experience
The PEARL trial — the first randomized, placebo-controlled year-long study of rapamycin in healthy adults, reported in 2024–2025 — enrolled around 115 people averaging 60 years old. Adverse events, including serious ones, were no different between rapamycin and placebo, and there was no excess of infections. Observational cohorts of longevity users report the same: mouth ulcers, yes — see the mouth ulcers page — but not a pattern of increased infection.
That is reassuring and limited. A year is not a decade, a hundred people is not a thousand, and no one has yet run a trial sized to detect a modest increase in serious infections.
The rules we apply
Live vaccines are avoided while on rapamycin. The live vaccines an adult might encounter — the older shingles vaccine (now largely replaced), MMR, yellow fever, the nasal flu spray, oral typhoid — are avoided in anyone on an mTOR inhibitor, because the immune suppression, however modest, could in theory allow the weakened vaccine strain to cause disease. The modern shingles vaccine and the standard flu shot are inactivated and are not affected by this rule. Travel vaccines are a specific conversation before travel.
Inactivated vaccines are encouraged, not discouraged. There is no reason to skip a flu, COVID, pneumonia or shingles vaccine on rapamycin, and the paradox above suggests the response may be at least as good.
Rapamycin is paused during a significant infection. Anything with a fever, anything needing antibiotics, and anything that is not resolving normally: stop the rapamycin, treat the infection, tell us, and restart on advice. This is not a judgement call to make alone.
It is paused around surgery. Rapamycin slows wound healing, and the main page covers the surgical rule. Dental surgery counts.
Tell your other clinicians. An antibiotic prescribed by an urgent-care clinician who does not know you are on rapamycin may interact with it — some common antibiotics and antifungals raise rapamycin levels substantially. The main page covers interactions.
Frequently asked questions
At transplant doses, continuously, yes. In the intermittent pattern used for longevity, the year-long PEARL trial found no excess of infections or serious adverse events versus placebo. Longer and larger data do not yet exist.
Inactivated vaccines — flu shot, COVID, pneumonia, the modern shingles vaccine — yes. Live vaccines — MMR, yellow fever, nasal flu spray, oral typhoid — are avoided while on it.
In a 2014 trial, older adults on a related mTOR inhibitor for six weeks had about a 20% stronger antibody response to a flu vaccine. It is a striking result that has not been confirmed at scale with rapamycin itself.
For anything with a fever, anything needing antibiotics, or anything not resolving normally — yes, and tell us. Restart on advice, not by default.
Yes. It is paused before surgery, including dental surgery, and restarted after healing.
Several common ones raise rapamycin levels considerably. Any prescriber treating an infection needs to know you take it.
Where this fits in your plan
The Rapamycin page covers evidence, candidacy, interactions and monitoring. If you take it, a current vaccination record is part of the file, and an infection is a reason to message us the same day.
We measure first. Then we act.
References
- Mannick JB et al. mTOR inhibition improves immune function in the elderly. Science Translational Medicine 2014;6:268ra179.
- Mannick JB et al. TORC1 inhibition enhances immune function and reduces infections in the elderly. Science Translational Medicine 2018;10:eaaq1564.
- Mannick JB et al. Targeting the biology of aging with mTOR inhibitors to improve immune function in older adults: phase 2b and phase 3 randomized trials. Lancet Healthy Longevity 2021;2:e250–e262.
- PEARL trial: Influence of rapamycin on safety and healthspan metrics after one year. Aging 2025.
- Rapamune (sirolimus) prescribing information — Warnings: immunosuppression, infections, impaired wound healing; live vaccines.
- CDC. General Best Practice Guidelines for Immunization: Altered Immunocompetence.
How we write and review our content
ACT 2 Health provides clinician-led care. Treatments are available only to eligible patients following clinical evaluation and within applicable regulations. This content is educational and is not medical advice. Individual results vary.
Care is delivered via telemedicine by healthcare professionals licensed in the state where the patient is located. Services are available only in states where our providers are licensed.
A fever or infection while on rapamycin should be reported promptly.