BLOG: mRNA vaccines – safe or something to worry about?

We often have reservations about things that are new and unknown to us. During the coronavirus pandemic, there have been misgivings about vaccines. For example, the media have asked whether mRNA vaccines can change our genetic code or have other serious health effects.  My attitude towards vaccines reflects my broad and varied experience as a researcher. My work has involved RNA for more than 20 years. I’m therefore very familiar with the technology and mechanism of action of mRNA vaccines. I also know that this technology is safe.

The mRNA molecule is familiar to cells and disappears from the human body quickly

As its name suggests (messenger ribonucleic acid), the mRNA molecule serves as a messenger in cells. The mRNA transmits information packed in the DNA so that cells can make proteins from amino acids (Figure 1). For cells, this has been business as usual for billions of years – the foundation of life. In that sense, mRNA is certainly not a new invention.

The mRNA in coronavirus vaccines is a single-stranded RNA molecule that cannot integrate into the genome. In other words, there is no reason to fear that it could cause cancer or affect fertility or the genome of future children. The half-life of the mRNA is measured in hours. Once the mRNA has completed its mission by producing coronavirus spike protein to trigger a defence response, it breaks down and disappears from the body.

The changes made to the mRNA in coronavirus vaccines enable the formation of the desired defence response

The changes made to the RNA in coronavirus vaccines have raised concerns. Can the changes cause spike protein to accumulate as a toxin in the body, resulting in adverse effects? 

The changes made to the mRNA in coronavirus vaccines have enabled the vaccines to work as effectively as possible. The RNA consists of four bases, and the desired protein is formed based on their order. The cells in our body react strongly to foreign RNA to prevent viruses from using cells to produce copies of themselves.

The tolerability of vaccines and the desired immune response targeted at the spike protein can be improved by making changes to the mRNA.

In mRNA vaccines, the mRNA code has been modified by changing two amino acids in the resulting spike protein. The goal is to form as many neutralising antibodies as possible.

The idea of modifying amino acids did not come out of thin air. It was based on researchers’ previous work to understand the structure of the spike protein in the coronavirus that causes MERS (Middle East Respiratory Syndrome). The modification does not result in anything dangerous. In the case of mRNA vaccines in particular, it is certain that the production of spike protein only lasts for a short time. This eliminates the possibility of foreign protein accumulating in any part of the body.

Other key components of mRNA vaccines

The lipid nanoparticle is another key component of coronavirus vaccines. The term may sound suspicious, but there is nothing strange or unusual about lipid nanoparticles. The human body is made up of cells, and the cell membranes consist of fat molecules. The mRNA in the vaccine must therefore be packed so that it penetrates the cell membrane. The lipid particle enables the vaccine to pass through the cell membrane, so the mRNA can enter the cytoplasm and turn into spike protein.

Another component of mRNA vaccines is polyethylene glycol (PEG) for longer shelf life. This has also caused concern, as some people are known to have antibodies to PEG. We should therefore be prepared to treat allergic reactions that mRNA vaccines may cause. Polyethylene glycol is also known as macrogol, which sounds more familiar to many people. Macrogol is used as an active ingredient in constipation medicines, for example. Here we again find a familiar and safe ingredient.

Understanding the cell biology related to coronavirus vaccines at the molecular level is not easy – not even for experts in the field.  My background in cellular and molecular biology research helps me to understand the ways in which various vaccine technologies work. This gives me confidence to critically assess any adverse effects related to vaccines.

After having examined in detail how RNA works in cells, I can assure you that there is no need to fear side effects occurring several years after having been vaccinated. As soon as one month after the vaccination, the mRNA vaccine is only a memory in our body – in the form of memory cells responsible for the long-term maintenance of antibodies and the defence capacity of the body.

Mika Rämet
Professor of Paediatrics and Experimental Immunology

Tampere University’s Vaccine Research Center