New BÜHLMANN Polyethylene glycol (PEG) Allergens for potential vaccine reactions

June 17, 2021

BÜHLMANN is proud to extend the portfolio of the Polyethylene glycol (PEG) related allergens for the Flow CAST® basophil activation assay with the release of PEG 4000 (order code, BAG2-CPEG).

The public interest of PEG hypersensitivity reactions is rising, since more and more cases of anaphylactic reactions to the COVID-19 vaccine are described. Polyethylene glycols (PEG) are ingredients of the lipid formulation in the mRNA based COVID-19 vaccines and are suspected to be the primary cause of allergic reactions1,2. First international recommendations clearly advice that patients with hypersensitivity reactions to PEG and the cross reactive polysorbate should not be vaccinated.

The Flow CAST® is a powerful laboratory test to investigate the patients’ hypersensitivity reactions to drugs. With first cases of anaphylactic reactions to COVID-19 vaccine starting to appear during the last winter1 and with the acceleration of the global vaccination campaign, we received many requests from experts in the field, who asked for standardized PEG allergens to investigate hypersensitivity reactions to PEG in patients.

Allergic reactions to vaccines are rare events. Although a recent report showed that the occurrence of anaphylaxis might be greater than what was reported by the Center for Disease Control and Prevention (CDC), it still remains rare. Therefore, it should not deter patients from getting a vaccination3, but maintenance of vaccine safety requires a proactive approach to maintain public confidence1.

Vigilance and clinical management of patients during vaccinations are essential, and this approach should also include the understanding of any allergic or adverse reaction mechanisms of action, the identification of the culprit substance in the vaccine formulation, and a proposed warning for people at risk, before getting the vaccine.

Flow CAST® basophil activation testing is a powerful laboratory testing opportunity to investigate a potential patient’s hypersensitivity reaction to PEG4.5.

Basophil Activation Test (BAT)

The Basophil Activation Test (BAT) an in vivo allergic reaction in a safe blood collection tube. The basophils are the allergic cells present in the human blood and are easily accessible by drawing a sample of venous blood from an individual. Each suspected allergen, like PEG, can be tested in a BAT by adding the allergen to a small amount of blood and incubating it with a dedicated stimulation buffer. A specific basophil activation by the allergen typically results in the basophils degranulation with the release of pro-inflammatory mediators as well as the expression of activation markers. The BAT test takes the advantages of the flow cytometry technique to identify basophils directly in whole blood without the need of cell separation and to quantify the percentage of activated cells by the expression of such activation markers like CD63.

The Basophil Activation Test is a reliable biomarker for potential hypersensitivity reactions of potential allergenic substances in vivo and represents a safe and accurate allergy test requiring a blood sample from an individual only.

The knowledge of PEG hypersensitivity reactions is limited compared to other drugs. For a long time, PEG has been considered safe and therefore it is being used in several drugs, cosmetics, food preparations and medical devices.  Its role as a hidden allergen has been discovered only recently. So far, also the typical diagnostic investigation that relies on a skin prick test with a series of PEG at different molecular weights is still not standardized6.

BAT assays, such as Flow CAST® are safe and non-invasive alternatives to allergic tests in-vivo and validated support to investigate PEG hypersensitivity reactions in the context of adverse reactions to COVID-19 vaccines. Adverse reactions to the first COVID-19 vaccine were documented in late December 20207, which were the “catalyst” for BÜHLMANN to investigate diagnostics for said hypersensitivity reactions.

For that reason, we are diligently working in the development and release of a PEG related package of CAST® allergens for our Flow CAST®. Since it is known that PEGs at different molecular weights may result in different reactivity of patient basophils, we are working on more than one PEG to maximize the chance to detect an allergic patient response.

With the release of the PEG 4000 our actual portfolio of allergens to investigate PEG hypersensitivity includes now:

  • PEG 4000 (order code, BAG2-CPEG), linear PEG of Molecular Weight in the range of 3500-4500

 

  • PEG 2000 (order code, BAG2-CPEG2), linear PEG of Molecular Weight in the range of 1900-2200

 

  • DMG PEG 2000, 1,2-Dimyristoyl-rac-glycero-3-methoxypolyethylene glycol-2000 (order code, BAG2-CPEG3), lipid component with a PEG 2000 chain used in the preparation of nanomedicines and liposomes like the mRNA COVID-19 vaccine of Moderna

To immediately respond to the increasing requests from the specialists in the field, the product is available as a Research Use Only (RUO) version now. The certification of such allergens as CE-IVD is expected soon.

Key Literature List PEG Allergen

References:

  1. Castells, M. C. & Phillips, E. J. Maintaining Safety with SARS-CoV-2 Vaccines. N. Engl. J. Med. 1–7 (2020) doi:10.1056/nejmra2035343.
  2. Cabanillas, B., Akdis, C. & Novak, N. Allergic reactions to the first COVID‐19 vaccine: a potential role of Polyethylene glycol? Allergy 0–1 (2020) doi:10.1111/all.14711.
  3. Blumenthal, K. G. et al. Acute Allergic Reactions to mRNA COVID-19 Vaccines. JAMA – J. Am. Med. Assoc. E1–E3 (2021) doi:10.1001/jama.2021.3976.
  4. Wenande, E. & Garvey, L. H. Immediate-type hypersensitivity to polyethylene glycols: a review. Clin. Exp. Allergy 46, 907–922 (2016).
  5. Cerdá, V. J., Pacheco, R. R., Witek, J. D., De La Calle, F. M. M. & De La Sen Fernández, M. L. Immediate hypersensitivity to polyethylene glycols in unrelated products: When standardization in the nomenclature of the components of drugs, cosmetics, and food becomes necessary. Allergy, Asthma Clin. Immunol. 15, 1–5 (2019).
  6. Stone, C. A. et al. Immediate Hypersensitivity to Polyethylene Glycols and Polysorbates: More Common Than We Have Recognized. J. Allergy Clin. Immunol. Pract. 7, 1533-1540.e8 (2019).
  7. Garvey, L. H. & Nasser, S. Anaphylaxis to the first COVID-19 vaccine: is polyethylene glycol (PEG) the culprit?Br. J. Anaesth. 8–10 (2021) doi:10.1016/j.bja.2020.12.020.