Basophil reactivity to BNT162b2 is mediated by PEGylated lipid nanoparticles in PEG allergic patients

J Allergy Clin Immunol. 2021 May 12;S0091-6749(21)00731-4. doi: 10.1016/j.jaci.2021.04.032. Online ahead of print.


Background: The mechanisms underpinning allergic reactions to the BNT162b2 (Pfizer) COVID-19 vaccine remain unknown, with polyethylene glycol (PEG) contained in the lipid nanoparticle suspected as being the cause.

Objective: To evaluate the performance of skin testing and basophil activation testing to PEG, polysorbate 80, BNT162b2 and AZD1222 (Astra-Zeneca) COVID-19 vaccines in patients with a history of PEG allergy.

Methods: Three known PEG allergic participants and three healthy controls were recruited, and evaluated for hypersensitivity to the BNT162b2 and AZD1222 vaccines and related compounds by skin testing and basophil activation measured by CD63 upregulation using flow cytometry.

Results: We found that the BNT162b2 vaccine induced positive skin tests in PEG allergic patients, whereas traditional PEG skin testing was negative in two of three patients. One patient was found to be co-sensitized to both the BNT162b2 and AZD1222 vaccines due to cross-reactive PEG and polysorbate allergy. The BNT162b2 vaccine, but not PEG alone, induced dose-dependent activation of all patients' basophils ex vivo. Similar basophil activation could be induced by PEGylated liposomal doxorubicin, suggesting that PEGlyated lipids within nanoparticles, and not PEG in its native state, are able to efficiently induce degranulation.

Conclusions: Our findings implicate PEG, as covalently modified within the vaccine lipid nanoparticle, as a potential trigger of anaphylaxis to BNT162b2.