Genetic vaccines for COVID-19. Is it possible to integrate viral RNA into the human genome? [WE EXPLAIN]

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The closer to the planned date of vaccination against COVID-19, the more questions about the safety of modern vaccines. Many concerns are caused by the name itself – a genetic vaccine – associated with interference in genes. Is the technology used for the first time safe? And if it doesn’t hurt now, maybe it will have some side effects in the future? Not so scary a devil. Vaccines based on mRNA are the result of many years of research that went in one direction. In an interview with Medonet, Dr. hab. n. med. Maciej Przybylski.

1. Scientists developing modern vaccines want to eliminate all elements of the preparation over which they have incomplete control
2. – Genetic vaccines contain a short fragment of the so-called messenger RNA (mRNA) that encodes one selected viral protein – explains Dr. Przybylski.
3. Dr. Maciej Przybylski: – It should also be mentioned that the lipid component of the vaccine may cause short-term adverse reactions after vaccination, such as fatigue or muscle pain
4. The problem that we have to deal with when starting the vaccination campaign are low-temperature freezers, which are not on the list of standard equipment for nurses’ offices in POZ centers.
5. You can find more such stories on the TvoiLokony home page

Monika Zieleniewska, MedTvoiLokony: To understand the scientists’ strategy that led them towards genetic vaccines, let’s look at the preparations that we have been using for years.

Dr hab. Maciej Przybylski, MD, PhD: Some conventional vaccines contain a virus that can reproduce normally in cells but has been completely deprived of its ability to cause disease, i.e. has been attenuated. This is how vaccines work, for example against mumps, measles, rubella or chickenpox viruses.

Are all traditional vaccines based on similar assumptions?

Another type of vaccine contains a specific part of the virus, called an antigen, most often it is a protein that our body recognizes as foreign so that it can react quickly and effectively to the proteins of the natural virus in the future. Thus, some vaccines contain complete viruses, while others contain isolated, purified viral proteins.

It is a specific protein, one that we know causes a strong immune response against this virus. This protein is purified from the pool of viruses obtained naturally, for example in cell culture, and then administered as a vaccine. The flu vaccine is a good example.

However, this is not the end, we can also take the gene of such a protein and, for example, force bacteria or yeasts through genetic engineering to produce this protein. In this situation, they also need to be cleaned thoroughly. The purified protein is called recombinant, and this is what is given as a vaccine. Example – Hepatitis B vaccine.

And this type of vaccine has been used around the world for a long time.

The first vaccine against smallpox was used as early as 1796. However, this vaccine was unique because it was created long before the development of modern biology, as a result of the genius intuition of the British physician Edward Jenner.

However, the first vaccines based on scientific research were developed before the Second World War. We must be aware that the introduction of vaccinations results in the fact that a given infectious disease resolves, although sometimes not completely. We already have an example of a disease that was completely extinct after vaccination, otherwise it was eradicated. It’s real smallpox. We are also very close to eradication in polio, that is, acute widespread childhood paralysis. Everyone is expecting the WHO to announce the complete elimination of this infectious disease thanks to vaccination at any moment.

However, in most cases, vaccination leads to a sharp drop in the number of cases. And here, mumps, measles or rubella will be a very good example. In Poland alone, tens, sometimes hundreds of thousands of cases were reported annually, and after the introduction of vaccines, the number of cases dropped significantly. Unfortunately, over the past decade there have been anti-vaccination movements and we have a problem again. At our own request, we fund ourselves the return of infectious diseases.

Vaccine opponents believe that vaccines do more harm than good.

Vaccines have been used for a long time and it is known that there is always a risk of an adverse vaccine reaction. Post-vaccination adverse reactions are a whole series of body reactions, ranging from pain or redness at the injection site, through a headache, and on a high body temperature for a day or two. However, these symptoms disappear quickly.

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This is really all?

There is one more thing that needs to be said about the greater danger. In the case of attenuated vaccines, that is, those where an infectious but non-virulent virus is administered, the virus may revert back to a virulent form. Then it can cause something close to a natural disease. Such cases are observed once in a million doses of the vaccine administered, sometimes even less frequently. However, if we were to get sick with what we vaccinate, then depending on the disease, the symptoms would affect from 20 to 90 percent. people who have become infected. Each disease is then associated with the risk of complications that are dangerous to health and even life. I am talking about measles, for example. However, the risk is there because we are administering a virus that normally replicates in cells. Therefore, where possible, one switches from the attenuated variant to a variant that no longer contains infectious virus.

Has vaccine development technology moved towards genetic preparation for the same reason?

This is the result of our growing knowledge of biological processes, we learn more and more about the functioning of the cell and the whole organism. And therefore research is moving in this direction – for a long time, it started almost 30 years ago. Of course, we didn’t have technical ways to implement these ideas back then.

The idea was right, but it took 30 years to turn it into reality. So the genetic vaccine was not born the day before yesterday, it is the result of long, painstaking research.

What innovations does the new type of vaccine bring?

The point is to eliminate as much as possible those elements over which we have incomplete control. In the case of an attenuated virus, we do not control it at all after we have given the vaccine. The breakthrough step was the development of recombinant vaccine technology, where there is in fact no microorganism (virus or bacteria), only a protein based on the coding gene. This protein is produced in the body, such as baker’s yeast, and then purified. Thanks to this, we avoid the entire biological mess related to the multiplication and purification of the virus. We do not have the virus, but we do have its purified protein obtained in a different, non-pathogenic organism.

But did scientists go even further?

They eliminated the whole aspect of the virus as such and decided to get our own cells to produce this one viral protein of choice. Now there is no way at all that an infectious virus will emerge. There is only one gene of his choice that is known to encode a viral protein that stimulates immunity well. In order to achieve the goal, they put a short fragment of the so-called messenger RNA (mRNA) that encodes this one viral protein of choice. Then the ribosomes of our cells start to produce this protein themselves. Later, and this is another advantage of genetic vaccines, the protein will be recognized as an antigen that has arisen inside the cell.

Why is this an advantage?

Because our immunity will be prepared in advance that the infection will be viral. Our body will respond better and faster to this infection.

Since there are only advantages, where do you think the resistance to new vaccines comes from?

The potential downside, which is what people fear, is the possibility of incorporating viral RNA into the human genome. In a cell of the human body, this is impossible because it requires a very specific set of enzymes that are not present in such a cell. Another feature of RNA is that it is quickly destroyed inside the cell. This is the natural way of things for any RNA. For example, mRNA is produced over and over in every cell, as it is the information matrix on which the cell produces its own proteins. After completing the task, the mRNA is destroyed. If necessary, the cell synthesizes another copy of the required mRNA.

And we, in the vaccine, suggest what the cells are supposed to synthesize?

Yes, we artificially give genetic information on the basis of which the virus protein will be produced. It is important that the lifespan of such mRNA is short, it is very quickly destroyed.

How, then, does the cell remember that it is a protein from a dangerous virus that needs to be eliminated?

The cell does not have to remember anything, it is completely different from that. It is there to make proteins identical to the viral ones. Then these proteins, as in the case of any contact with a foreign antigen, will be recognized by the so-called professional antigen presenting cells. They will take them to the lymphatic tissue and show that they have found a foreign protein. They will present them to helper T cells. These are our commanders when it comes to specific immunity. The helper lymphocytes will distribute the antigen information between cytotoxic lymphocytes and antibody-producing B lymphocytes, and only then will we remember to defend ourselves against this virus. All vaccines work according to this pattern.

So we only changed the technology. But it is probably not perfect, since we store vaccines at -80 degrees Celsius?

This is a disadvantage, but we use this solution for some drugs. The problem is that mRNA vaccines are administered inside lipid nanoparticles. These lipid sheaths can be compared to micellar fluid, they are micelles, microscopic vesicles made of a fatty film, which have mRNA inside. In this form, it is easily absorbed by the cell. The problem is that this lipid layer breaks down during prolonged storage at higher temperatures.

It should also be mentioned that the lipid component of the vaccine may cause short-term adverse reactions after vaccination, such as fatigue or muscle aches. Our body reacts badly to lipid compounds administered intramuscularly – this is the way in which the mRNA vaccine is administered. Technology is constantly being developed in this direction so that nanoparticles are as neutral to the body as possible.

I wonder if we will be able to provide the COVID-19 vaccines with the right conditions …

This will require retrofitting vaccination centers. It is known that in order for vaccination to be considered effective from the formal and legal point of view, the vaccine must be stored properly, and low-temperature freezers are not standard equipment for nurses’ offices in primary health care centers. This problem will have to be dealt with somehow, either by increasing the temperature resistance of this vaccine or by providing freezers.

Let’s summarize, is it worth getting vaccinated?

The vaccine is the result of 30 years of work by many scientists, and its safety had to be tested during long-term and meticulous clinical trials. Vaccination gives us immunity bypassing very effectively all the disadvantages associated with infection with the virus itself. It is hard to imagine it posing a threat to the body, no matter how wild the scenarios our imagination suggests. From a biological point of view, this is not possible.

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