ImmunologyTier 2Medical Sciences concept

Vaccination immunology - mRNA vaccine components and allergy contraindications (polyethylene glycol)

Core concept

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Lipid nanoparticle carrying modified mRNA (N1-methylpseudouridine)

-> endocytosed by host cell
-> released into CYTOPLASM - no nuclear entry, no transcription step, no reverse transcription
-> ribosome translates it into the antigen (SARS-CoV-2 spike, stabilised in prefusion conformation)
-> antigen displayed and shed
-> MHC I -> CD8 and MHC II -> CD4/antibody
-> mRNA degraded within days; the protein within weeks

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mRNA cannot integrate into the genome - it never enters the nucleus and human cells have no reverse transcriptase or integrase
The LNP is also the adjuvant - it drives the innate response and much of the reactogenicity

Components

Component	Role	Allergy relevance
Modified mRNA	Encodes the antigen; pseudouridine reduces innate sensing and raises translation	-
Ionisable cationic lipid	Complexes mRNA, mediates endosomal escape	Reactogenicity
PEGylated lipid (PEG-2000)	Stabilises the particle	The implicated allergen in Pfizer and Moderna vaccines
Cholesterol, phospholipid (DSPC)	Structure	-
Sucrose, tris/phosphate buffer	Cryoprotectant	-

No egg, no gelatin, no latex, no preservative, no adjuvant salt, no live virus, no antibiotic
PEG (macrogol) is the culprit and it is everywhere: bowel preparation (Movicol, Glycoprep, PicoPrep), laxatives, depot methylprednisolone, some tablet coatings, cosmetics, ultrasound gel
- Cross-reactivity with polysorbate 80 (structurally related) - polysorbate is in the AstraZeneca/Vaxzevria and Novavax vaccines, and in many biologics
- So a PEG-allergic patient may also react to polysorbate-containing alternatives - refer, do not simply switch
Anaphylaxis rate ~2.5-11 per million doses - higher than most vaccines but still very rare; onset usually within 15-30 min

Contraindications (true)
- Anaphylaxis to a previous dose of the same vaccine
- Anaphylaxis to a component - PEG/macrogol or polysorbate
- -> specialist allergy referral for skin testing to PEG and polysorbate, and supervised vaccination or an alternative platform
NOT contraindications: egg allergy, food or drug allergy generally, family history of allergy, mastocytosis, prior local or delayed reaction, urticaria after a previous dose
Myocarditis/pericarditis - the other adverse event to know
- Highest in males 16-30, after dose 2, within 1-5 days; roughly 1-2 per 10,000 in the highest-risk group
- Usually mild and self-limiting; risk of myocarditis from SARS-CoV-2 infection itself is higher
- -> lengthen the interdose interval, prefer an alternative platform after a confirmed episode
Observation for 15 minutes (30 minutes after a prior immediate reaction, or with a history of anaphylaxis to anything)
The same platform is now used for RSV vaccines and in cancer vaccine trials - the allergy issue is the excipient, and it will follow the platform

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