Matrix RNA in COVID-19 vaccines: what is this new technology for medicine and is it dangerous

COVID-19 vaccination is rapidly beginning around the world. Several countries and companies have created their own vaccines for the virus, and in different ways. ForumDaily tried to find out what is so hidden in vaccines and why some of them became revolutionary in medicine.

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Types of vaccines

There are three areas in which scientists usually try to create a vaccine: inactivated vaccines with viral proteins, live recombinant (vector) vaccines, and gene vaccines (mRNA vaccines).

In the first case, we are talking about vaccines containing proteins of "killed" viruses, which for this purpose are heated or treated with ionizing radiation or disinfectants. The body recognizes "dead" viruses and reacts to them by making antibodies, but not causing disease. Using this technology, for example, polio, hepatitis B, diphtheria, pertussis, tetanus or flu vaccines have been created.

Live vector vaccines are created on the basis of harmless, weakened viruses (vectors), in which the gene is inserted - a small section of the SARS-CoV-2 genome. Vectors serve as carriers of pathogens for delivery into cells. Once there, the genetically modified viruses multiply inside the cells and trigger an immune response against the SARS-CoV-2 proteins. In this way, vaccines against measles, chickenpox, mumps and rubella were created. This is the most common type of vaccine, and the Russian Sputnik vaccine works by this type.

If pathogens are capable of rapid genetic changes or pose the threat of new infectious diseases, as was the case with Zika fever or SARS SARS, classic antiviral vaccines are not particularly effective. Therefore, great hopes are placed on the so-called mRNA vaccines.

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The principle of these vaccines is that they contain a viral molecule - messenger RNA (mRNA), enclosed in a lipid nanoparticle. Once in the body, mRNA enters the cell and begins to synthesize pathogen-specific antigens that provoke an immune response.

The good thing about the technology is that mRNA is a fairly simple molecule, so it can be produced relatively quickly and in very large quantities. However, this method also raises the greatest concerns. The problem is that old, time-tested vaccines of this type simply do not exist, so it is not known how it will behave in the human body.

The medical revolution

It was the creation of the third type of vaccine that became a breakthrough in medicine.

It was made by Moderna, which has been on the biotechnology market for only 10 years and has not registered a single drug.

On the one hand, this is not surprising: the development of this company is based solely on the use of messenger RNA, and not a single drug created using this technology has yet been approved for vaccination of people.

On the other hand, it is all the more impressive that the effectiveness of the innovative mRNA-1273 vaccine is close to 100% for both mild and severe cases.

The messenger RNA vaccine was also made by Pfizer, an American pharmaceutical giant with a century and a half history, which earned millions of dollars back in the Second World War on the production of penicillin.

Expert Opinion

Microbiologist Konstantin Severinov spoke with the journalists of the publication New Newspaper and told interesting facts about vaccines against COVID-19.

“The vaccines from Pfizer and Moderna are truly revolutionary. They are based on a new approach, which is finally brought to mind after almost 20 years of research. In principle, it allows vaccine candidates to be brewed in a very short time against almost any pathogen and any new pathogen. Provided that his genome is known, his genetic sequence is known, ”Konstantin believes.

He also talked about how this method works.

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“The central dogma of molecular biology states that genes in DNA encode proteins through an intermediate molecule called RNA. A copy of the messenger RNA is removed from the DNA, and from it, like a template, special cellular machines-ribosomes make the protein encoded in it. That is, in fact, it is an instruction for the cell to make a protein. Many copies of a protein can be made from one RNA molecule, the expert explains. “But RNA only works inside the cell. At the same time, it is very unstable in itself, easily falling apart. Therefore, for delivery to the cells of the body, it is placed in a special stabilizing capsule using complex and interesting manipulations. After receiving messenger RNA, the cells of the body will begin to produce S-protein. That is, human cells will appear in the body, which for some time, until the RNA breaks down, will produce S-protein, while the coronavirus itself will not be in the human body. "

It turns out that instead of traditional vaccines, where a piece of the virus is injected into the body, which is needed by the immune system to produce antibodies, now "instructions for making such pieces" are introduced into the body.

“This will not happen for long, because the life of RNA in a cell is short. But for a while, some of our cells will make the S-protein of the coronavirus. The immune system will begin to recognize these cells: they say, what kind of disgrace it is, like a normal cell, but produces some kind of nonsense. Antibodies will begin to appear. The cells by themselves will be destroyed so that they don't produce what they don't need, but the immune system will remember the S-protein. And if it enters the body in the future as part of a virus, the immune response will develop quickly, ”Severinov details.

“At the same time, there is no infection in the body, but there is just information about what it consists of. In any case, the immune system will work as nature intended, ”the microbiologist specifies.

He also explained why a vaccine against any antigen could be quickly developed based on an mRNA strategy.

“Molecular biology is now very developed, many technological solutions are known and put on stream. You just need to know the genetic sequence of the pathogen. In the case of the coronavirus, it was determined exactly a year ago, a few weeks after the first cases of the disease appeared, '' Konstantin said. - Further - a matter of technology: bioinformatic analysis, methods of computer biology are used to identify genes encoding certain proteins. And making messenger RNA that encodes a particular protein is not difficult. Methods for introducing such an RNA molecule into human cells have now also been developed. Therefore, candidate vaccines based on mRNA can be baked like cakes. ”

At the same time, the expert notes: this does not mean that the tests will no longer be needed, the advantage is that the invention of the vaccine itself will take much less time.

“Of course, tests are needed. But candidate vaccines can be made very quickly. You don't need to adapt the virus to make it less vicious. There is no need to build up a huge number of viruses, as is the case with the killed and weakened. No huge fermenters needed. Everything is done in standard laboratory conditions. Not everyone realized this to the end, but science, of course, has passed a new milestone, and this is wonderful, "Severinov states.

But revolutionary vaccines are difficult to transport and store. The Pfizer vaccine requires a temperature of minus 70 degrees, otherwise the very lipid capsule in which the molecule sits will be destroyed, and the RNA will fall apart. For the same Moderna you need minus 20.

“In infrastructurally developed or small countries, the problem is quite solvable. In Israel, 20 people per hundred were vaccinated with the Pfizer vaccine, it was done very quickly, ”the expert said.

Such a quick solution to a problem that scientists have been working on for 20 years, the microbiologist explains by a sharp increase in funding for the industry.

“People really worked on this for a long time, just some technological problems were not solved. The feeling is that it was possible to solve a number of problems with a very large amount of money that was thrown in at the same time, - stressed Konstantin. - When they say that there was little time, this is not entirely true. The development of mRNA vaccines in the United States took much less time than usual, primarily because science is very advanced, and this allowed the production of candidate vaccines very quickly.

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“The government has given Moderna and Pfizer guarantees that, in any case, even if the vaccine is ineffective, it will compensate for the costs of obtaining the product. Therefore, the companies actually developed the vaccine before registration in parallel with clinical trials. And when it turned out that clinical trials confirm safety and efficacy, it turned out that both vaccines are already available, you can apply for permission to use them. At the same time, clinical trials and the decision on registration were carried out and made by people independent of the state. If the vaccines turned out to be inoperative, the state would lose money, but not the developers and manufacturers, ”the expert explains.

Directly Konstantin Severinov would like to be vaccinated with Moderna, but since he does not have access to this vaccine, he will make it Sputnik.

“All of these vaccines seem to work. If I had a choice, I would be vaccinated with an American one, but in the United States there is now a very strict system of access to a vaccine, university professors are not being vaccinated yet, ”says Severinov. - Therefore, I, apparently, will be vaccinated with "Sputnik". According to him, albeit with a scandal, there was still an article in Lancet, a prestigious medical journal, about the results of combined stages I and II. "

Five interesting facts about the mRNA vaccine

MRNA vaccine technology is not entirely new

Vaccines, such as the inactivated polio vaccine or most influenza vaccines, use inactivated viruses to force a person's immune system to respond to this disease-causing organism. Others, such as the hepatitis B vaccine, instead inject a separate protein made by the body to trigger a similar response. Horizon Magazine.

However, mRNA vaccines trick the body into producing the viral protein itself, which in turn triggers an immune response.

Although the COVID-19 vaccines produced by Pfizer / BioNTech and Moderna are the first mRNA vaccines to pass all stages of clinical trials and receive a license to use, the technology is no longer new.

Human trials of cancer vaccines using the same mRNA technology have been underway since at least 2011. “If there was a real problem with the technology, we would surely have seen it earlier,” said Michelle Goldman, professor of immunology.

Because the technology can be deployed extremely quickly and clinical trials have become so successful, mRNA platforms, according to the immunologist, will serve as an important means of preparing for future epidemics.

mRNA vaccines do not alter DNA

Some fear that mRNA vaccines could alter people's DNA. But this idea is "completely false" and "has no scientific basis," says Professor Goldman and explains: "The vaccine mRNA will not enter the nucleus of cells where our DNA is located."

As soon as the introduced mRNA enters the human cell, it quickly decomposes and remains in the body for only a couple of days. Therefore, he explains, people need two injections to develop a better immune response.

mRNA vaccines are very specific

The new coronavirus, or SARS-CoV-2, is complex, and different parts of the virus cause the immune system to produce different antibodies to neutralize the virus.

If an unvaccinated person becomes infected with the virus, he produces antibodies that prevent the virus from entering human cells. They can also generate antibodies that have little effect. And in some cases, the human body is capable of producing antibodies that actually help the virus enter cells.

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mRNA vaccines are much more specific. They are only designed to elicit an immune response against a viral protein, which is just one component of the viral membrane and allows the virus to enter our cells.

To make sure that this is the case, researchers are careful to ensure that the vaccine does not elicit an unwanted immune response.

“This has not yet been demonstrated for COWID-19 vaccines. But it remains important to ensure that the immune response elicited by the vaccine is focused on the viral protein, ”said Professor Goldman.

During clinical trials and approvals, no corners were cut

Vaccines are tested in stages, from animal testing to 3-phase human trials: Phase-1, Phase-2 and Phase-3.

More than 40 people participated in the third phase of the Pfizer / BioNTech vaccine trial. It began in July and will continue to collect efficacy and safety data for another two years.

According to Professor Goldman, safety issues that can affect a significant number of vaccines most often occur within two months.

But the newness of the technology scares many doctors. A nurse from New York, for example, refused to be vaccinated against COVID-19because, according to her, the long-term impact of mRNA technology on the human body has not yet been assessed.

Regulatory authorities reviewed data from COVID-19 vaccine trials faster than usual. And they did it before the end of the last phase of testing. But when reviewing the data, they did not change their requirements, which did not affect the safety of the vaccine. “I really don't think the corners have been cut from a safety standpoint,” said Professor Goldman.

The process was going faster than usual because the researchers had already created an mRNA platform (a way to deliver viral mRNA into the body) for a vaccine against cancer and others. That is, it could be applied as soon as the genomic sequence of the virus becomes publicly available.

Companies and governments also took the risk of producing large quantities of vaccines even before the first rounds of experiments were completed, which meant they were ready to start large human trials as soon as results were available.

“This is a financial risk, because if you are wrong, all is lost. This is why the risk is shared between private companies and the government, ”concluded Professor Goldman.

The vaccine triggers an inflammatory response

While working, the vaccine partially triggers local inflammatory reactions that trigger the immune system. This means that it is normal for many people to experience pain at the injection site and sometimes fever and discomfort for one or two days after vaccination.

A November poll in 15 countries found that 54% of people are concerned about the potential side effects of the vaccine.

One unwanted response to the Pfizer-BioNTech mRNA vaccine came to light on the first day of mass vaccinations in the UK after two people with a history of significant allergies reacted to the injection. The UK regulator has updated its guidelines to indicate that people with a history of anaphylaxis to medications or food should not be vaccinated.

In clinical trials, 0,63% of people who received the Pfizer-BioNTech vaccine experienced allergic reactions and 0,5% who received a placebo.

“My biggest concern is that people will use potential side effects as an argument against vaccination,” said Professor Goldman. "But the highest risk right now, especially for vulnerable people, is not getting vaccinated."

Technology perspectives

Messenger RNA technology can also help prevent other complex diseases such as cancer or HIV. If mRNA passes the pandemic test, it will open up a whole new field in medicine. Forbes.

Several companies are working to adapt mRNA for vaccines against influenza, heart failure, cystic fibrosis (an inherited disease), cytomegalovirus (a viral disease), and even HIV. The flu vaccine can be combined with other vaccines and can literally deal with all seasonal winter illnesses with just one shot, said Moderna CEO Stefan Bansel.

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“We are entering the era of mRNA therapy. There will be more investments and more resources in this direction, ”predicts former Harvard biologist and Moderna shareholder Derrick Rossi. He believes that in 10-20 years all vaccines against infectious diseases will be based on mRNA. According to the forecast of the co-founder of BioNTech Ugur Sakhin, in two to three years the first cancer drugs using this technology can receive approval.

Among others, Moderna, AstraZeneca and the world's largest cancer drug manufacturer Roche are working on an mRNA-based cancer vaccine with BioNTech. The German startup is working with a charity foundation of Bill Gates and his wife, Melinda, to develop an HIV vaccine.

But there is no guarantee that the forecasts of specialists and company executives about mRNA vaccines will be right. All vaccines, except for COVID-19, are still in the early stages of testing. And if substances can work with infectious diseases, such as coronavirus, then it will be more difficult with cancer, since it has learned to bypass the protection of immunity.

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Not just a vaccine: amazing scientific discoveries in 2020

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