mRNA vaccines are safe: here's why

Covid-19 vaccines are among the safest and most effective ever made: they have undergone rigorous studies and strict approval criteria, and their technology is the result of decades of development by researchers around the world.

Let's see why they are safe and why we should not be afraid of alleged long-term effects with the help of Prof. Roberto Burioni, full professor of Microbiology and Virology at the Vita-Salute San Raffaele University in Milan.

There are two reasons most often cited by those who chose not to get vaccinated for Covid-19: the speed of approval (implying lower levels of quality and safety) and the fear of side effects that could emerge over the years.

However, after a year of administration – and almost 3 billion people vaccinated in full doses, many for more than 10 months – the vaccines for Covid-19 are among the most effective and safe ever made: the protection they provide from serious disease exceeds 90% and side effects are very rare.

Not only have Covid-19 vaccines not been hastily developed (they are the result of decades of research, including clinical research), but historically, long-term side effects have never occurred.

Historical evidence on the safety of vaccines

"We must first start with historical evidence, which is incontrovertible: vaccines are, of all types of drugs, the safest. This is also true for adverse effects that appear within hours, days or weeks of administration, but it is even more impressive when we look at the long-term effects - explains Prof. Burioni.

In fact, there are no cases of vaccines that have had undesirable effects that appeared later than eight weeks after administration. Indeed, in general they manifest themselves, despite their rarity, within a few hours or days."

Naturally, the surveillance system continues well beyond this period of time: phase IV ("post-marketing") of drug approval consists precisely in monitoring the safety and secondary effects of the vaccine over the years and on a heterogeneous and constantly increasing population. In any case, these are extremely low risks.

Why do vaccines have no long-term effects?

The fundamental reason why vaccines produce rare adverse effects within a few weeks away of administration is that they are drugs to be taken few times over lifetime: for this reason, the molecules contained within vaccines remain in our body for a very short time.

On the contrary, many drugs – for example those to treat hypertension, heart failure, type 1 diabetes, asthma – must be taken daily, sometimes for a lifetime. Daily intake is essential precisely to keep the amount of active ingredient in circulation in the blood constant, which would otherwise be eliminated from the body within a few hours or days.

"In the case of mRNA vaccines, which represent more than 70% of the administrations, the residence time in the organism is particularly short, because they are very fragile molecules, which are denatured and dissolved rapidly, as well as the copies of Spike protein produced from mRNA,” explains Burioni.

This means that, within one day of administration, a tiny amount of the vaccine content remained in our body. How then does it protect us from Covid-19? Thanks to the reaction and memory capacity of our immune system.

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The function of vaccines is in fact to stimulate the immune system to memorize the identikit of the virus: in the event of subsequent exposure to that virus, it will be equipped to activate a rapid and efficient response to prevent infection.

"This training process takes place largely in the first days after meeting the antigen [the component of viruses, bacteria or parasites recognized by the immune system to defend the organism, Ed] and in any case is completed within six, maximum eight weeks. This is why any adverse effects due to this activation process occur in this time window and not later."

Vaccines approved thanks to a fruitful collaboration

The innovative messenger RNA (mRNA) vaccines are among the first anti-Covid-19 vaccines developed: since they were approved in record times, this gave the false impression of a hastily developed technology.

In reality, there has been no relaxation of the strict criteria for approval: the approval process of the anti-Covid-19 vaccines has complied with all the stages required by the regulatory bodies.

These vaccines are the result of decades of studies whose initial goal was to fight cancer: to train the immune system to better recognize cancer cells.

"Not only that, but the technology was advanced enough at the time of the outbreak of the Covid-19 pandemic to have already entered the clinical trial phase for some types of cancer, showing a very high safety profile," explains Burioni.

Illustrative diagram of the essential elements that make up mRNA vaccines. A lipid envelope encloses a messenger RNA molecule that carries the sequence of the SARS-CoV-2 virus Spike protein. In the mRNA molecule, the uridine nitrogen base (U) is replaced by a pseudouridine (ψ). For further information on the composition of mRNA vaccines, read our news.

The different experimental phases were conducted in parallel rather than sequentially, investing in the production of numerous vaccine candidates. The production costs were covered thanks to the economic resources largely coming from public funding and private philanthropists and the collaboration of all the bodies - academic, pharmaceutical, regulatory and governmental - involved in the process.

Furthermore, the transmission of the virus on a global scale has made it possible to find thousands of volunteers in a very short time and to study the protective effect of the vaccine very quickly.

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"In a sense, the Covid-19 pandemic has shown us that the process of developing a vaccine - when there is adequate investment and collaboration among public, private and citizens - can be much faster than what we are, unfortunately, get used to. A lesson for the fight against other infectious diseases still awaiting an effective vaccine” Burioni concludes.