Once vaccines have become a reality, the next “trending topic” in this pandemic period is the safety provided by the first approved vaccines based on the mRNA technology. On dealing with this issue, we can only rely on the information provided by the experts in this field and, if additionally, such information is published in a very well reputed review, the better.

A scientific article published a few months ago in the New England Journal of Medicine, entitled “Maintaining safety with SARS- coV-2 Vaccines” by Dr Mariana C. Castells and Elisabeth J. Philipps is of interest as it draws the attention to some cases where anaphylaxis occurred when administering the mRNA vaccine from Pfizer- BioNTech. In addition, some of these cases have been reported with Moderna vaccine but they are still under analysis.

For the sake of clarification, mRNA vaccines instead of putting a weakened or inactivated germ into our bodies, they teach our cells how to make a protein (or even just a piece of protein) which is present in the surface of the virus causing Covid-19 (Spike protein), and the production of this protein triggers an immune response. The Spike protein allows the virus to bind to the cells and permits entry of the virus in the human body. The immune response generated by the mRNA vaccines which produces antibodies, is what protects us from being infected, preventing the real virus from entering in our body.

A summary of these article would be as follows:

Those two vaccines were approved under the emergency use authorisation process which is a mechanism to facilitate the availability and use of medical countermeasures (such as vaccines) during this pandemic situation.

In relation to the Pfizer-BioNTech vaccine, the UK Health Authorities (MHRA) was the first to authorize emergency use of it and within 24 hours after the start of mass vaccination two probable cases of anaphylaxis were reported (the two cases had previous food and drug allergies). The USA health authorities (FDA) were the second to authorize it and within 24 hours from starting vaccination, a case in Alaska of anaphylaxis was reported from a person with no known allergies. Since this case in Alaska, several more cases of anaphylaxis associated with Pfizer- BioNTech vaccine were reported in the USA after vaccination of almost two million health care workers, and the incidences of anaphylaxis with the Pfizer-BioNTech vaccine appears to be 10 times as high as the incidence reports with previous vaccines (i.e. Pfizer 1 in 100,000 and other vaccines 1 in 1,000,000). In relation to Moderna mRNA vaccine, it was first authorized on 18 December 2020 and we know now (at the date of publication of this newsletter) that similar cases of anaphylaxis have been already reported in the US.

As a response to the two cases in the UK, the UK health authorities issued a pause on the vaccination to exclude people with history of anaphylactic reaction to food, drugs or vaccines. Furthermore the Centers for Disease Control and Prevention issued an advice recommending exclusion from vaccination (either from the Pfizer or the Modern vaccines) to any person with severe or immediate allergic reaction associated to any of the vaccine component including  PEG (polyethylene glycol) or PEG derivatives.

Anaphylaxis is a serious multisystem reaction with rapid onset, which can lead to death by asphyxiation, cardiovascular collapse and other complications. It requires quick response and treatment with epinephrine to stop the progression of the life-threatening symptoms.

The clinical manifestations of the two UK cases and the one in USA occurred within minutes after the injection with the symptoms typical of anaphylaxis and all responded to epinephrine. The authors of the article state that anaphylaxis reactions are a rare event for most known vaccines and that some allergic reactions might be caused either by the excipients used in the vaccine or by the antigen contained in the vaccine (i.e. Antigen is a portion of the virus or bacteria that induces the immunity response of the body by generating antibodies). Historically, anaphylaxis has been associated to the excipients contained in the vaccines (eggs, gelatine or latex).

In the mRNA vaccines from Pfizer-BioNTech and Moderna the nanoparticles envelope is made of PEG (i.e. necessary to prevent that the mRNA in the vaccine is degraded and to facilitate in vivo delivery). Although the technology behind the mRNA vaccines is not new, the fact is that these vaccines are the first to receive an emergency use authorisation and therefore there is no prior experience, which may provide information on the allergic reactions associated with them. The presence of PEG 2000 in the vaccines has raised the concern that this component may be the cause of the anaphylaxis in the cases reported and to date no other vaccines using PEG as excipient has been widespread used. Although it appears that, this excipient is more likely that the active drug to cause such anaphylaxis.

However, it remains also unknown if a patient with anaphylaxis reaction to Pfizer vaccines, the risk of anaphylaxis with Moderna vaccine. Furthermore, the implication for future use of SARS-CoV-2 vaccines using excipients similar to PEG (such a polysorbate 80) are also unknown. Therefore, until further investigations are performed it has been recommended that patients either with (i) anaphylactic reaction to any component of these mRNA vaccines (ii) patients with reactions associated to PEG and (iii) patients with anaphylaxis reaction after receiving either Pfizer-BioNTech or Moderna vaccine should avoid all a mRNA vaccines containing PEG and all products containing PEG or polysorbate for the time being.

In any case, the authors raise the attention to the fact that side effects to vaccines are common (local inflammation, fever, chills, malaise, joint pains, fatigue) but that allergic reactions are rare. In any post emergency use authorisation programs, adverse events not identified in the clinical trials are to be expected when mass vaccination is initiated. In this case with the SARS-CoV-2 vaccines already on the market and with the new coming vaccines, strategies have to be developed to maximize effectiveness and safety at an individual and population level and that during this pandemic situation is ongoing it is critical to focus on safe and efficient approached to implement mass vaccination.

Vaccines based in mRNA Technology may lead to a new era of personalized vaccinology where it can be tailored the safest and most effective vaccines on an individual population level but up to date in the world of Covid-19  many questions on safety and immunity remain unanswered such as how long immunity last? Which component of the vaccine is responsible for allergic reactions? In any event, measures have to be adopted to inform a strategic and systemic approach to vaccine safety.