mRNA vaccines: How do they work?

THE SCIENCE BEHIND mRNA VACCINES

Let’s start with the basics: what is in an mRNA vaccine?

Before we go straight to the science behind an mRNA vaccine, we should ask ourselves:

What is in a vial of mRNA vaccine?

Even though reaching the final formulation is far from trivial, the final components found in a vial of mRNA vaccine can be classified into just 3 groups: mRNA, Lipids and Excipients. Do you want to know more about the role of each ingredient in the outcome of the vaccine?

mRNA

As expected, this is the active ingredient in the vaccine as it is translated in the body to create the protein that induces an immune response.

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Lipids

They are arranged as vessels that envelop the mRNA to protect it from degradation and help to deliver it into the cells.

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Excipients

Them being mainly salts and stabilizers, their role is to maintain the embodiment of the vaccine.

Do you want to learn more about the whole process, beginning to end?

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mRNA acts as middleman between DNA and protein production.

As it is universally known, DNA is the molecule in charge of storing the genetic information of cells. The so-called “genes” are fragments of DNA that contain the instructions to make proteins, large molecules which play vital roles within the cell, from catalyzing chemical reactions to structural functions. However, even though DNA contains the information to synthesize proteins, these are not directly synthesized using DNA as a template. That is where mRNA comes into play.

mRNA stands for messenger RNA, and that is precisely what it does. It carries the message encoded in DNA that contains the instructions to synthesize proteins. Thus, the steps for protein production would roughly be as follows:

  • When the body identifies the need to produce a protein, instead of using DNA as a template, mRNA is produced as an intermediate (messenger) from DNA in a process called “transcription”.

  • This mRNA will then suffer some essential changes that will render what is known as mature mRNA.

  • This is then transported to the ribosomes, the machinery used in the cell to produce proteins.

  • Therein, the process referred to as “translation” takes place, thus producing the protein of interest from the mRNA template.

So now that you know about mRNA, should we jump to the other main ingredient of the vaccine?

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mRNA too unstable for therapeutic use? Not anymore.

One could ask why, with all the potential described above, mRNA has only recently been started to be used after having been studied for more than 10 years. The key here is that, compared to its precursor, DNA, mRNA shows a much higher degree of instability. This instability, which has probably been the biggest stumbling block for the use of mRNA as a therapeutic, has only recently been overcome with the development of a new mRNA delivery system using lipid nano-particles (LNPs).

These lipids are essentially fats that can be combined to create these LNPs, which resemble small vesicles, that can allocate mRNA in its interior preventing its degradation and allowing for efficient transport to the target cell.

Lipid nano-particles (LNPs) ensure an efficient transport to the target cell

mRNA vaccines take a fresh approach to more traditional ones.

So, let’s recap: DNA is transcribed into mRNA, which in turn is translated into proteins. The question is, how can we use this natural mechanism to our advantage? How do you turn this into a vaccine?

Most vaccines have traditionally contained a weakened pathogen (or part of it) which, although incapable of causing disease, can help the body create antibodies to fight a potential future infection.

Although the principle is similar, mRNA vaccines use a cannier approach:

  1. Protein selection. Instead of using the whole pathogen, a protein that is characteristic of that pathogen is carefully selected as the target.
  2. Design and synthesis of mRNA sequence. That protein is sequenced and the mRNA that would lead to its synthesis is designed and synthesized. This process is known as reverse engineering.
  3. Formulation. The synthesized mRNA is properly formulated to ensure is stable and delivery to the cell.
  4. Delivery. After injection, the formulated mRNA fuses with the cell membrane and delivers the mRNA into the cell.
  5. Protein production. Once into the cell, the mRNA is translated into the protein that was previously selected as the target. This process takes place by the ribosome.
  6. Immune response. The presence of this protein alerts the immune system creating an immune response. After this protein is presented to the immune system a specialized group of cells are recruited, eventually creating antibodies against that protein. Since that protein is characteristic of that pathogen, if infected by it in the future the body would already be prepared to fight the infection.
  1. Protein selection. Instead of using the whole pathogen, a protein that is characteristic of that pathogen is carefully selected as target.
  2. Design and synthesis of mRNA sequence. That protein is sequenced and the mRNA that would lead to its synthesis is designed and synthesized. This process is known as reverse engineering.
  3. Formulation. The synthesized mRNA is properly formulated to ensure is stable.
  4. Delivery. After injection, the formulated mRNA fuses with the cell membrane and delivers the mRNA into the cell.
  5. Protein production. Once injected, the mRNA promotes the production of that protein that was previously selected as target. This process takes place in the ribosome.
  6. Immune response. The presence of this protein alerts the immune system creating an immune response. After this protein is presented to the immune system a specialized group of cells are recruited, eventually creating antibodies against that protein. Since that protein is characteristic of that pathogen, if infected by it in the future the body would already be prepared to fight the infection.

“The obvious main advantage of mRNA vaccines is that individuals that have been injected with an mRNA vaccine are not exposed to the pathogens, so there is no risk of infection by the vaccine. Also, since mRNA does not enter the nucleus of the cell, there is no possibility of a DNA alteration.”