Corona vaccination: How do the new mRNA vaccines work?

Corona vaccination: How do the new mRNA vaccines work?

Two of the vaccines used in the European Union use what is known as mRNA technology. Specifically, these are the vaccines from BioNTech and Pfizer (BNT162b2 or Comirnaty®) and Moderna (mRNA-1273) from the USA. But how does an mRNA vaccine against coronavirus work, how does it differ from previously known vaccines, and what are the current findings on possible side effects?

What is mRNA?

The abbreviation “mRNA” stands for “messenger RNA”, i.e. “messenger ribonucleic acid”. The mRNA has typically the following function in the body:

  • Within the cell nucleus is the genetic information in the form of  DNA. Among other things, it contains information on the structure of proteins.
  • However, the structure of these proteins takes place outside the cell nucleus, namely on the so-called ribosomes. These are parts of the cells where proteins are made.
  • To transmit this information from the DNA to the ribosomes, mRNA is produced as a messenger substance. This can leave the cell nucleus and share the information with the ribosomes.

In this way, the DNA remains protected in the cell nucleus, and the genetic information can still be read and processed at different locations within the cell.

 

How does an mRNA vaccine work?

Like that used against COVID-19, an mRNA vaccine contains information about part of the coronavirus. It is, so to speak, the blueprint for a piece of the so-called spike protein, which the virus needs in order to bind to the surface of cells and infect them.

The mRNA of the vaccine and the information it contains about the spike protein can be read out and replicated by the cell. SARS-CoV-2 protein fragments are formed, i.e. small pieces of protein that resemble the virus (or its spike proteins) from the body’s point of view.

The body’s immune system reacts to the foreign virus components with an immune response. This includes, among other things, the formation of antibodies, i.e. certain substances in the blood that prevent future infection. In contrast to the natural course of a disease, vaccination does not cause any COVID-19 symptoms, and the virus does not multiply.

The vaccine mRNA completely breaks down in the body after a few days. If SARS-CoV-2 viruses enter the body after vaccination, an immune response is immediately triggered. The spread of the virus in the body is prevented, and thus, the development of COVID-19 symptoms is prevented.

How effective are mRNA vaccines?

According to the companies, the vaccines from BioNTech/Pfizer and Moderna offer a vaccination protection of about 95 per cent. This means that the vaccine protects 95 per cent against serious illnesses. The mRNA vaccines are also highly effective against mild to moderately severe courses (95 per cent at BioNTech/Pfizer, 90 per cent at Moderna). Both mRNA vaccines also provide 90 per cent protection against severe illnesses from the more contagious delta variant of the coronavirus.

A British study examined the effectiveness of the BioNTech/Pfizer vaccine against the omicron variant. The researchers concluded that there was no longer adequate protection against a symptomatic infection with the omicron mutation almost four months after the second vaccination. The protective effect of symptomatic courses was given as 34 per cent. After the booster vaccination, the protective effect improved to around 70 per cent. However, only about 580 people were examined as part of the study.

Vaccinated people can still infect unvaccinated people. However, the risk is shallow two weeks after the second vaccination dose. According to the Robert Koch Institute, the probability of infection is lower than in asymptomatic infected people with a negative antigen rapid test.

 

Can an mRNA vaccine affect the genome?

A fear often expressed is that the modified mRNA could influence the genetic material, i.e. the DNA. According to the Robert Koch Institute and the Paul Ehrlich Institute, it is not possible for the mRNA to affect the DNA in the cell nucleus:

  • The mRNA is outside the nucleus, but the DNA is inside.
  • In addition, the structure of mRNA and DNA is chemically so different that the DNA could not easily incorporate the mRNA.
  • Also, mRNA from healthy human cells cannot be transcribed into DNA.

An exception is certain viruses that have the enzyme “reverse transcriptase”. These include, for example, the HI virus ( HIV ) or the hepatitis B virus. These viruses can convert RNA into DNA using the enzyme mentioned. In theory, a simultaneous infection with one of these viruses could transform the vaccine mRNA into DNA.

But even then, incorporation into the DNA remains unlikely. This would require further reactions within the cell that do not occur naturally. The development of an autoimmune disease,  which some fear as a result of this process, is considered extremely unlikely.

In addition, it is essential to know that a change in the genetic material of individual body cells almost always has no consequences since the body’s mechanisms continuously correct such changes.

The vaccine also plays no role in inheritance since it does not interfere with the human germ line (i.e., egg and sperm cells). So, the vaccine cannot make you infertile.

Are other risks and side effects of the vaccines known?

After the completion of the phase 3 studies and with the start of the first vaccinations in the population, it has been possible to determine mainly mild side effects in vaccinated people. The most commonly observed side effects included temporary body aches, swelling and redness at the vaccination site, headaches and fatigue. More than 40,000 people took part in the study by the manufacturers BioNTech/Pfizer and around 30,000 in Moderna.

Serious side effects only occur in sporadic cases. These included cardiac arrhythmias in one person vaccinated with the BioNTech/Pfizer vaccine and paralysis of a facial nerve in three people treated with the Moderna vaccine. However, it is not clear whether these reactions were caused by the vaccine or by other triggers.

Since vaccination began, there have been very few cases of severe allergic reactions to the BioNTech/Pfizer vaccine in different countries. Therefore, people with solid and known allergies should clarify individually whether the vaccine suits them. In a patient questionnaire, existing allergies are queried before the vaccination. Post-injection follow-up ensures that medical attention can be provided quickly during an allergic reaction.

In sporadic cases, heart muscle ( myocarditis ) or pericardium inflammation occurs after mRNA vaccine vaccination. Women and men under the age of 30 are particularly affected by this side effect. Since heart muscle and pericarditis occur more frequently after vaccination with the Moderna vaccine, the Standing Vaccination Committee (STIKO) recommends vaccination with the BioNTech/Pfizer vaccine for people under 30 and pregnant women. This also applies to second and third vaccinations.

Symptoms of heart muscle inflammation include rapid heartbeat or stumbling, chest pain or shortness of breath. Typical signs of pericarditis are pain behind the breastbone, which can also radiate to the back or left arm. Medical advice should be sought if such symptoms occur concerning the coronavirus vaccination.

With a view to possible long-term effects, a reliable statement can only be made due to the short investigation period. Late effects are side effects that only occur after a more extended period.

According to current scientific knowledge, however, it can be assumed that the corona vaccines will not have any long-term effects. This concerns how vaccines work: unlike medicines, vaccines are not administered constantly over a long period. In addition, they do not accumulate in the body but are broken down very quickly. For this reason, side effects occur after a few weeks at the latest. So far, vaccines have never had a long-term impact.

Long-term consequences must be distinguished from thisThese are side effects that appear shortly after vaccination but last for a more extended period.

Why is a new type of vaccine used against Corona?

A significant advantage of mRNA vaccines over other vaccines is the short production time. The production of an mRNA vaccine is much faster and more flexible than with other methods. This also results from the possibility of taking steps without working with infectious coronavirus and using so-called vaccination boosters. In this way, a large number of vaccine doses can be produced in a short time.

 

Cooling is a unique feature during storage.

A unique feature of mRNA vaccines, however, is the required cooling. The Moderna vaccine lasts for 30 days at refrigerator temperatures and otherwise needs to be stored at -25 to -15 degrees Celsius.

The BioNTech/Pfizer vaccine can also be stored at these values ​​for one month. This makes storage in regular pharmaceutical refrigerators and freezers possible. At -90 to -60 degrees, the vaccine can also be kept for six months.

Why was the development so fast compared to other vaccines?

The development of a vaccine can often extend over several years. In comparison, the development of the mRNA vaccine against the coronavirus was highly rapid. There are the following reasons for this:

  • Financing: In pharmaceutical companies, the development of a vaccine is often ensured by partners from the industry. Government funds were provided for the development of the vaccine against the coronavirus. The development means hardly any financial risk for the companies involved and can be pushed ahead with high pressure.
  • Faster approval procedures:  As social pressure is very high around the world, the authorities concerned are focusing on processing the existing applications for means to combat the coronavirus as quickly as possible. For example, the Federal Institute for Drugs and Medical Devices (BfArM) has assigned significantly more staff to review clinical studies and approve the corresponding drugs. In doing so, testing standards were not lowered, and phases in the development of the vaccines were not skipped.
  • Existing knowledge:  Due to the remarkable similarity between the SARS coronavirus and the MERS coronavirus, SARS-CoV-2 could draw on existing knowledge about this virus form. Clinical studies were already underway for both, dealing with replicating the spike protein. Research has also been done on mRNA vaccines. Therefore, The approach is familiar but has been further developed.

When were the vaccines approved?

Approval of the vaccine by the European Medicines Agency (EMA)  is necessary for the approval of vaccines in Germany. After the examination, the associated Committee for Medicinal Products for Human Use (CHMP) makes a recommendation regarding approval, which the EU Commission then decides on. However, this is usually based on the recommendations of the CHMP.

BioNTech and Moderna submitted applications for approval of their mRNA vaccines to the EMA on December 1, 2020. On December 21, EMA recommended conditional approval of BioNTech/Pfizer’s vaccine. The same day, the EU Commission followed this recommendation and approved the European vaccine. The first vaccinations in Germany were carried out on December 26.

The recommendation for the EMA’s approval of Moderna’s vaccine and the decision on conditional approval by the EU Commission was made on January 6, 2021. A few days later, the vaccine was also delivered to Germany and vaccination began.

On May 31, 2021, the BioNTech/Pfizer vaccine was also approved for use in EU children aged 12 and over. On July 23, Moderna’s vaccine was approved for this age group. In Germany, the STIKO initially only recommended vaccination for children with certain pre-existing conditions. The recommendation was changed on August 16, 2021: It now applies to all children and young people aged 12 and over.

In November 2021, the EMA recommended vaccinating children aged five to eleven with the BioNTech/Pfizer vaccine Comirnaty ®. In these cases, a third of the usual dose for adults is vaccinated. The STIKO followed this recommendation in December 2021 but initially limited it to children who have contact with risk patients or suffer from previous illnesses. In May 2022, STIKO changed its recommendation and now advises all healthy children aged five to eleven to have a one-time vaccination, preferably with a reduced dose of Comirnaty ®. In the case of pre-existing conditions, a complete immunization and a booster are recommended. In the event of contact with risk groups, a double vaccination is advisable. Moderna’s vaccine can now also be used from the age of six.

In October 2022, the European Commission converted the conditional approval of both vaccines into a standard authorization. This means that the approval no longer has to be renewed every year. The vaccination recommendation for children also changed in October 2022. The EU Commission has also approved reducing doses of the vaccines from Moderna and BioNTech Pfizer for children from six months.

 

booster vaccination

The Standing Vaccination Commission recommends that all people aged 12 and over refresh their vaccination protection with a booster vaccination with an mRNA vaccine – regardless of which vaccine was used for the primary immunization. This third vaccination should be carried out at the earliest six months after the second vaccination, in exceptional cases, even after four months.

Currently (as of October 2022), a fourth vaccination for people from risk groups and a fifth vaccination for people who are particularly at risk (including residents of older adults’s homes and the very old) are recommended by the Standing Vaccination Commission. In autumn 2022, the EU Commission approved BioNTech/Pfizer and Moderna vaccines adapted to the Omikron variants BA.1 or BA.4 and BA.5.

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