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Corona vaccines from Biontech / Pfizer and ModernaHow mRNA vaccines work and work

The first reactions from the professional world and from politics to the recently presented study results by the companies Biontech / Pfizer and Moderna were downright euphoric:

"For me, that was the best news I've ever heard in the medical field during the pandemic." "28 million people are expected to be vaccinated with this new vaccine next year." "The vaccine appears to be very well tolerated and it appears to be very effective." "We'll have a vaccine. We won't have to live like this forever."

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Both vaccine candidates are based on a modern concept that has only been developed in recent years. The so-called "messenger RNA", or mRNA for short, plays the central role here, explains Leif Erik Sander, head of the Infection Immunology and Vaccine Research Research Group at the Charitè in Berlin:

"In this case, the genome of the new Sars coronavirus was used as a template and a messenger RNA was produced for a protein; the spike protein, which is responsible for the coronaviruses to attach to the cell surface. This is coded in this messenger RNA molecule, and an injection with this messenger RNA induces the body to produce these small virus proteins itself. And then, for example, to develop antibodies or other immune responses. And this is basically how vaccination works. "

Our interlocutor Leif Erik Sander from the Charitè, Berlin (Photo: Charité / Jaqueline Hirscher)

The human body makes virus proteins itself

"The human body can manufacture its own medicine with mRNA technology" - this is how the biotech company CureVac puts it. And Leif Erik Sander also sees this as an advantage of the concept:

"If you had to produce the pure protein yourself, it would be a bit more complex at first. And if you inoculate the protein, the spike protein, then it is only in the place where you inoculate it for a certain period of time and then disappears Again. The mRNA may be there a little longer, and that is often beneficial for immunological memory generation. "

The infectiologist sees another advantage in the flexibility of the method; such as the possibility of adapting a vaccine to the genome of a pathogen very quickly. In principle, however, many other approaches are "very attractive in vaccine development and have also been successful for years and decades."

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Can genetic information from viruses pass into human DNA?

Despite all the elegance of the process - the smuggling of viral protein construction instructions into the human body naturally raises questions about possible risks. Can the virus mRNA change the human genome? Is a carcinogenic, carcinogenic effect of exogenous mRNA conceivable?

At least on the first point, Leif Erik Sander is as good as certain - according to current knowledge, a transition from virus mRNA to human DNA is practically impossible: "This is a one-way street. The mRNAs that we administer get into our cells and there they get to the so-called ribosomes, where the proteins are put together. But they do not get into the cell nucleus. The cell nucleus has its own shell and our genetic material is located in the cell nucleus. This means that the mRNA does not come to the right place . " [*]

When asked about a possible cancer risk, the expert is neutral: "Of course, carcinogenic effects have to be checked for every new drug. But it is not the case that, because it is a nucleic acid, there is an increased risk of cancer here, what about others new drugs or vaccinations would go. "

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Is there a risk of infection-enhancing antibodies?

In connection with the relatively new mRNA vaccination concept, a potential risk is discussed, which infectiologists are familiar with from the development of vaccines against dengue fever.

The dengue virus occurs in four different serotypes, explains Leif Erik Sander. And "the antibodies that have been formed against one serotype are not quite optimal, they cannot completely prevent infection with another serotype, but they can cause damage because the virus then gets into cells that it would otherwise not get into This fear also existed with the new Sars coronavirus. But all the studies that I know about it from animal experiments and also from humans and from cell cultures do not suggest that we have this ADE, this 'Antibody dependent enhancement' phenomenon here or that we would have a problem there because of the vaccination. "

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How do the different vaccines differ?

In the case of the mRNA-based vaccines presented so far, there are significant differences in terms of the amount or concentration of the mRNA dose administered in each case. The advantages and disadvantages, also with regard to effectiveness and side effects - for example symptoms of a slight viral infection - are not yet quite foreseeable, according to Sander:

"There can certainly be a connection between the amount of RNA molecules that are given and the occurrence of this side effect. But that also has to do with how these RNA molecules are modified, what exactly they look like molecularly, so that the immune system does the better or worse. But, conversely, it can also mean that an activation of the immune system, which can lead to the side effects mentioned, then also leads to strong immunity. "

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What can the new vaccines actually do?

Both at Biontech / Pfizer and Moderna - so far, our level of information has only been based on press releases from the two companies, emphasizes Leif Erik Sander. And he also points out a problem with the study design.

In both studies, a reduction in corona infections with symptoms of around 95 percent was reported. But: "The question of whether asymptomatic infections and, much more importantly, infectiousness can be prevented - that has not been investigated in these studies, and we will not get these results from the studies. You would have the 30,000 or in the other study 40,000 test subjects have to swab and test regularly weekly or even more frequently. That was logistically not possible, and we will not get this information anytime soon. We will have to look at it in real life when these vaccines are actually approved and here in Germany Then you can try to compare how often asymptomatic infections are then still in vaccinated versus non-vaccinated people. "

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What does the development of mRNA vaccines mean for the other approaches?

"That is a very interesting question from various angles." That is how Leif Erik Sander sees it. As soon as there is approval for certain vaccines, in this case possibly the mRNA vaccines, the environment for all further approaches will change dramatically. The effectiveness test for a new procedure is usually based on a comparison with an ineffective procedure, a "placebo". And then ethical problems arise. In the case of Covid-19, a comparison with an untreated control group would be prohibited:

"If you want to test a new drug for a, I'll say a disease, for which there is already an effective drug, you just have to use the existing drug as a comparison. And then you do a so-called" non-inferiority test " In fact, the companies that are now later then have to get into a non-inferiority study, which means that the control group would receive one of the approved vaccines. And that is, in principle, logistically a little more difficult and certainly also Then a very high hurdle for vaccines, if a vaccine is already there that has proven 95 percent effectiveness, to come over it again. But it could well be that there are vaccines that are in certain population groups or with certain people work better. "

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[*] Editor's note: In this paragraph we have shortened a statement after consulting further scientific findings.