COVID-19: What is Behind the Cases of Allergic Responses to Pfizer’s Vaccine?

The COVID-19 vaccine by Pfizer, which has got emergency approval in a few countries, including the US and UK, has caused rare allergic reactions in a few recipients over the past two weeks. Till December 19, the US had recorded six cases – out of 2,72,001 recipients – of anaphylaxis (severe allergic reaction) with the UK recording two such cases.

Even if in a small proportion of cases, anaphylaxis can prove to be life threatening. The US NIAID (National Institute of Allergic and Infectious Diseases) organised several meetings to review the situation with representatives from Pfizer, Moderna, the FDA (Food and Drug Administration) and other scientists. These review meetings also discussed the possible causes of anaphylaxis. Pfizer has also recommended appropriate medical supervision and treatment to be made readily available in the case that someone develops anaphylaxis.

The vaccines developed by Pfizer & BioNTech and Moderna have used same platform, where mRNA (messenger RNA: a single-stranded molecule of RNA which corresponds to the genetic sequence of a gene) is inserted as the main ingredient. To deliver the mRNA into human cells, these vaccines use a compound known as PEG (Polyethylene glycol).

PEG had never been used in any vaccine until now, but other drugs this compound was used in previously triggered anaphylaxis in some cases. Experts believe that people who have had an earlier exposure to PEG may have a higher level of antibodies against it, putting them at a greater risk of developing anaphylaxis after being vaccinated.

The NIAID is collaborating with the FDA for a joint study to analyse the response of the vaccine recipients who have high level of antibodies against PEG, or had serious allergic responses to drugs and vaccines previously. Alkis Togias, branch chief of the asthma and airway biology branch of NIAID, reportedly said: “Until we know there is truly a PEG story, we need to be very careful in talking about that as a done deal.”

Notably, the clinical trials of both Moderna and Pfizer, where thousands of participants received their vaccine, did not record any serious adverse effects. However, importantly, both the trials excluded people that have a history of allergic response to components of the vaccine. People with food allergies or who were allergic to other drugs were not excluded. However, the number may have been underrepresented, scientists believe.

These mRNA vaccines against COVID-19 have lipid nanoparticles (LNP), which can ease the process of carrying the mRNA to human cells. The LNPs are chemically attached to the PEG compound. The LNPs are also called ‘adjuvant’ – an ingredient of the vaccine that helps boost the immune response.

PEG was earlier considered to be biologically inactive. However, recent research has changed the notion. A study led by Samuel Lai, a researcher with the UNC Eshelman School of Pharmacy, in 2016 suggested that about 72% of people have antibodies against PEG. Out of this number, seven per cent have a higher level of antibodies which can make them predisposed to anaphylactic reactions.

In 1999, Janos Szebeni discovered the mechanism of the adverse immune reaction against medicines containing nano particles, especially PEG. He described it as CARPA (Complement Activation Related Pseudoallergy), the non-specific immune response against PEG where the body, by mistake, considers it to be a virus.

The NIAID meetings have also had discussions on PEG-induced CARPA. However, there are differences of opinion, with many believing that the nano particles attached to PEG may trigger an allergic response via a mechanism other than CARPA.

With all the concerned authorities now looking into the matter, it is still not clear what the basis of the severe allergic responses in certain recipients of the vaccine is. However, the vaccination process has not been stalled due to the adverse effects that have emerged.