DNA and mRNA vaccines

DNA and mRNA vaccines represent a new generation of vaccines. They work in a completely different way than the well-known live and Inactivated vaccines.

What are mRNA and DNA vaccines?

The so-called mRNA vaccines (short: RNA vaccines) and DNA vaccines belong to the new class of gene-based vaccines. Intensive research and testing have been carried out on them for several years. In the wake of the corona pandemic, the first of them could be approved for immunization in the near future. Their principle of action differs from that of previous active ingredients.

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Classic live and inactivated vaccines bring weakened or killed or inactivated pathogens or parts of them into the body. The immune system reacts by forming specific antibodies against these foreign substances, which are known as antigens. The vaccinated person then develops immunity against the pathogen in question.

The new gene-based vaccines (DNA and mRNA vaccines) are different: They only smuggle the genetic blueprint for pathogen antigens into human cells. The cells then use these instructions to assemble the antigens themselves, which then trigger a specific immune response. In short: With gene-based vaccines, part of the complex vaccine production – the extraction of the antigens – is shifted from the laboratory to the human cells.

In addition to DNA and mRNA vaccines, the gene-based vaccines also include the so-called vector vaccines.

What are DNA and mRNA?

The abbreviation DNA stands for deoxyribonucleic acid. It is the carrier of genetic information in most organisms, including humans. The DNA is a double-stranded chain of four building blocks (called bases) arranged in pairs – similar to a rope ladder. The arrangement of the base pairs is a code for the construction plan, on the basis of which thousands of proteins are produced. They are the basis for the structure and function of the entire body.

In order to produce a certain protein, the cell first creates a “copy” of the DNA segment with the corresponding assembly instructions (gene) in the form of the single-stranded mRNA (messenger ribonucleic acid). This process is called transcription. The mRNA leaves the nucleus and is read in the cell plasma (cytoplasm). The protein in question is assembled on the basis of these assembly instructions. This “translation” of a genetic blueprint into a protein is called translation.

How do DNA and mRNA vaccines work?

The DNA blueprint (gene) for an antigen of a pathogen is in DNA vaccines. In the case of mRNA vaccines, this antigen blueprint is already available in the form of mRNA. And this is how immunization using a DNA or mRNA vaccine works:

mRNA vaccine

The mRNA can be present “naked” in the vaccine. However, the unpackaged mRNA is very sensitive and fragile. The body also breaks them down quickly, especially if the vaccine is injected into the muscle. This is why the mRNA is at least stabilized, for example by special protein molecules.

Usually, however, the mRNA blueprint for a pathogen antigen is in a package. On the one hand, this protects the fragile mRNA and, on the other hand, it facilitates the absorption of the foreign genetic material into a body cell. The packaging can consist of lipid nanoparticles, LNP for short (lipids = fats). Sometimes the foreign mRNA is also packaged in liposomes. These are small vesicles with an aqueous phase inside, which is surrounded by a lipid bilayer. This shell is chemically similar to a cell membrane.

After the foreign mRNA has been taken up in a cell, it is “read” directly in the cytoplasm. The cell then produces the corresponding pathogen protein (antigen). Usually it is a surface protein of the pathogen. Once it gets into the body, the immune system develops appropriate antibodies. This allows the body to react quickly to the pathogen itself in the event of a “real” infection. The vaccinated messenger RNA, in turn, is broken down again relatively quickly.

DNA vaccine

The DNA blueprint of a pathogen antigen is usually first built into a plasmid that cannot multiply. A plasmid is a small, circular DNA molecule that is typically found in bacteria.

The plasmid penetrates the body cells together with the antigen blueprint. With some DNA vaccines, this is supported by electroporation: At the puncture site, brief electrical pulses are used to briefly increase the permeability of the cell membranes, so that larger molecules such as foreign DNA can pass through more easily.

The DNA-antigen blueprint is then transcribed into mRNA in the cell nucleus. This leaves the nucleus and is translated into the corresponding antigen in the cytoplasm. Often it is a surface protein of the pathogen. It is then built into the shell of the cell. This foreign protein on the cell surface ultimately calls the immune system on the scene. It sets off a specific defense reaction. If the vaccinated person then becomes infected with the actual pathogen, the body can fight it faster.

Do vaccines save risks?

The main concern of some people is that mRNA and DNA vaccines could damage or alter the human genome. But so far there is no evidence of this. There is also no evidence that the vaccinations can cause diseases such as cancer.

To vaccinate or not? The fact checks:

  1. Vaccination discussion: the long-running hit – In Germany it is a long-running issue – the discussion about the benefits and risks of vaccinations. Few health topics are fought out with such passion as the second pike, which is supposed to protect the immune system against the attack of potentially life-threatening viruses. But what is really true of the arguments against the vaccine – and what speaks in favor of the immuno booster from the laboratory? We have put together the most important points.
  2. Better immune system? – Opponents of the vaccination say that unvaccinated children have a better immune system. In doing so, they forget that the vaccines give the immune cells in the body the same alarm signals as pathogenic viruses. But they are not infectious. Since the vaccine serums are also highly specific, the immune system of vaccinated children comes into contact with thousands of other pathogens every day, against which they have to defend themselves.
  3. It used to work without it! – “Lucky”, you could say. Infections with so-called childhood diseases do not always end well. Lung infections or inflammation of the brain and meninges are common complications of measles. And young men can become sterile from mumps, for example. Incidentally, unvaccinated adults raise concerns for children: So-called vaccination gaps are often to blame for the fact that epidemics can suddenly spread again.
  4. Avoidable risk? – In fact, vaccinations also put stress on the very young organism of babies. However, some infections – for example measles, whooping cough or Haemophilus influenzae – pose a particularly high risk for them. Early protection can be life-saving. Incidentally, there is no evidence that infants tolerate vaccinations less well than older children.
  5. Vaccinations make you sick – Many vaccines are made up of weakened (e.g. measles vaccine) or killed viruses. In this way the immune system is stimulated – the defense reaction often manifests itself in more or less pronounced symptoms of the disease. However, it is extremely rare for vaccines to actually make you sick with modern preparations.
  6. More allergies? – Some studies even seem to support the fact that vaccinations promote the development of allergies. However, proving an actual connection is difficult because many parents of those who oppose vaccination also keep other potentially allergenic factors away from their children by taking a more critical stance, for example on nutritional issues. On the other hand: In the former GDR, where vaccination was compulsory, particularly few children suffered from allergies.
  7. Hazardous additives – To make them more durable or to make them more effective, some vaccine serums actually contain formaldehyde, aluminum, mercury or other potentially toxic substances. However, in extremely low concentrations and below defined toxic limit values. Nevertheless, the industry has responded to the discussion and has now developed mercury-free vaccines.
  8. Antibiotics instead of vaccinations? – Many diseases are easier to treat with modern drugs than they were 30 or 40 years ago. However, antibiotics are not effective against viruses – in measles and the like, they can only fight those bacteria so-called opportunists, exploit the weakness of the immune system and cause complications. And with some bacteria, such as those responsible for tetanus meningitis or whooping cough, antibiotics hardly work.

Can mRNA vaccines change the human genome?

It is almost impossible that mRNA vaccines could damage or change the human genome. There are several reasons for this:

mRNA does not get into the cell nucleus: On the one hand, the foreign mRNA that has been smuggled into cells and the human DNA reside in different places – the mRNA remains in the cell plasma, while the human DNA lies in the cell nucleus. This is separated from the cell by a membrane. It is true that there are nuclear pores through which mRNA from the cell nucleus reaches the cell plasma. However, this is a complex process that runs in one direction. There is no way back.

mRNA cannot be integrated into DNA: On the other hand, mRNA and DNA have different chemical structures. Therefore, an mRNA cannot be incorporated into the human genome at all. This possibility would only exist if it was first rewritten in DNA. However, this would only be possible with the help of two enzymes (reverse transcriptase and integrase) – but a human cell normally does not have such enzymes.

Both enzymes are found in certain RNA viruses (such as the AIDS pathogen HIV). These are actually able to integrate their own genetic material into the genetic material of an infected human cell in this way. Theoretically, the following would be conceivable: If vaccine mRNA and the virus in a body cell coincidentally meet in a person infected with such an RNA virus, the mRNA introduced as a vaccine could actually be transcribed into DNA with the help of the viral enzymes.

In order for this to occur, which is very unlikely anyway, another factor would be necessary: ​​The transcription of mRNA into DNA requires a genetic start sequence (called “primer”), which the RNA viruses themselves bring with them. However, this primer is designed in such a way that only the virus’s own RNA genome is transcribed into DNA – and not another mRNA that is present in the cell.

It therefore seems impossible that an mRNA administered as a vaccine is accidentally transcribed into DNA and then incorporated into the human genome.

Can DNA vaccines change the human genome?

The situation is somewhat different with so-called DNA vaccines. The structure corresponds to that of human DNA. However, experts consider it extremely unlikely that they could actually be accidentally incorporated into the human genome: Years of experiments and experience with DNA vaccines already approved in veterinary medicine have provided no evidence of this.

Can mRNA and DNA vaccines cause autoimmune diseases?

The danger here does not seem to be any higher than with the classic live and inactivated vaccines. Any form of vaccination has an activating effect on the immune system. In very rare cases this can actually lead to an autoimmune reaction. After the swine flu vaccination, around 1,600 people later developed narcolepsy. Given the many millions of inoculated doses of the vaccine, the risk is negligible. In addition, viral diseases can themselves lead to an autoimmune disease.

Can mRNA and DNA vaccines damage the germ line?

No. The active ingredients of the vaccination usually do not reach the egg cells and sperm cells.

The benefits of DNA and mRNA vaccines

The fact that the pharmaceutical industry has invested a lot of work and money in the development of DNA and mRNA vaccines for years, among other things, to the fact that they can be produced more cheaply and, above all, much faster than conventional live and inactivated vaccines. For the latter, one must first cultivate pathogens in a laborious manner and in large quantities and then obtain their antigens.

In the case of gene-based vaccines such as DNA and mRNA vaccines, the body of the person being vaccinated is responsible for producing the antigen itself. The genetic antigen blueprints administered as a vaccination can be produced relatively quickly and easily in sufficient quantities and – if the pathogen is genetically modified (mutated) – quickly adapted.

Another advantage is that the transferred foreign genetic material does not remain in the body permanently. It is broken down by the body or disappears when the cells break down naturally. The foreign antigens are only produced for a short time. However, this time is sufficient for an immune response.

If one compares DNA and mRNA vaccines with one another, the latter have several advantages: Accidental incorporation into the human genome is even less likely than with DNA vaccines. In addition, strong enhancers (adjuvants) usually have to be added to DNA vaccines so that they trigger an effective immune response.

DNA and mRNA Vaccines: Current Research

So far, no mRNA or DNA vaccines have been approved for use in humans. Scientists have been researching their development for several years or even decades.

Pharmaceutical companies are currently working on DNA vaccines against around 20 different diseases, including flu, AIDS, hepatitis B, hepatitis C, and cervical cancer (usually caused by infection with HPV viruses). This also includes therapeutic vaccine candidates, i.e. those that can already be administered to sick people (e.g. cancer patients).

Various mRNA vaccines, for example against flu, rabies and the Zika virus, are also being worked on intensively.

Corona vaccine based on DNA or mRNA

Several gene-based vaccines are also being developed against the causative agent of the current corona pandemic, the Sars-CoV-2 virus. Some projects focus on a DNA vaccine against corona.

However, the development of mRNA vaccines against Sars-CoV-2 is more advanced. For two of these vaccine candidates, approval was submitted to the European Medicines Agency (EMA) at the end of November 2020. These mRNA-based corona vaccine candidates contain the blueprint for the so-called spike protein or part of it. This is a characteristic surface protein of Sars-CoV-2. Serious side effects have not yet been observed. Sometimes typical symptoms of an immune reaction occur such as pain at the injection site, fever, fatigue, chills or headache.

But not only DNA and mRNA vaccines are on the list of potential vaccine candidates against Sars-CoV-2. Scientists and pharmaceutical companies are also working on vector vaccines and conventional live and Inactivated vaccines.

Conclusion

There have been times during these past eight months when it seemed as if this present pandemic would become our future too, that we all might be consigned to living with restrictions and curtailment of our movements, that the life we knew before might indeed be gone for good. But that has changed and, yes, there is now the first light on the horizon —The roll-out of a vaccine against the coronavirus has begun in the UK. Chinese company Sinopharm said in November that around a million people in China had already received its vaccine. Mass vaccination also began in Russia this week. While in the United Arab Emirates (UAE), healthcare workers across the country heaved a sigh of relief as the UAE announced the mass use of Sinopharm’s Covid-19 vaccine, saying it was 86 per cent effective. The vaccine is available on a voluntary basis to anyone booking an appointment with Seha, however, details of nationwide inoculation are yet to be announced.  The hope is that if enough people take up the vaccine, herd immunity will be achieved and life will return to normal.