How do mRNA vaccines work?

Most vaccines contain an infectious pathogen or a part of it, but mRNA vaccines deliver the genetic instructions for our cells to make viral or bacterial proteins themselves. Our immune system responds to these and builds up immunity.

Messenger RNA (mRNA) is a single-stranded molecule naturally present in all of our cells. It carries the instructions for making proteins from our genes, located in the cell nucleus, to the cytoplasm, the main body of our cells.

Enzymes in the cytoplasm then translate the information stored in mRNA and make proteins.

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An mRNA vaccine delivers the instructions for making a bacterial or viral protein to our cells. Our immune system then responds to these proteins and develops the tools to react to future infections with the pathogen.

mRNA vaccine technology is not new, but there were no mRNA vaccines that had approval for use in humans until recently.

What is different about mRNA vaccines?

Some vaccines use a whole virus or bacterium to teach our bodies how to build up immunity to the pathogen. These pathogens are inactivated or attenuated, which means weakened. Other vaccines use parts of viruses or bacteria.

Recombinant vaccine technology employs yeast or bacterial cells to made many copies of a particular viral or bacterial protein or sometimes a small part of the protein.

mRNA vaccines bypass this step. They are chemically synthesized without the need for cells or pathogens, making the production process simpler. mRNA vaccines carry the information that allows our own cells to make the pathogen’s proteins or protein fragments themselves.

Importantly, mRNA vaccines only carry the information to make a small part of a pathogen. From this information, it is not possible for our cells to make the whole pathogen.

Both mRNA COVID-19 vaccines that Pfizer/BioNTech and Moderna have developed cannot cause COVID-19. They do not carry the full information for our cells to make the SARS-CoV-2 virus, and therefore, cannot cause an infection.

While the concept of mRNA vaccines may seem simple, the technology is rather sophisticated.

Addressing stability and safety

RNA is a notoriously fragile molecule. Delivering mRNA successfully to cells inside our bodies and ensuring that enzymes within our cells do not degrade it are key challenges in vaccine development.

Chemical modifications during the manufacturing process can significantly improve the stability of mRNA vaccines.

Encapsulating mRNA in lipid nanoparticles is one way to ensure that a vaccine can successfully enter cells and deliver the mRNA into the cytoplasm.

mRNA does not linger in our cells for long. Once it has passed its instructions to the protein-making machinery in our cells, enzymes called ribonucleases (RNases) degrade the mRNA.

It is not possible for mRNA to move into the nucleus of a cell as it lacks the signals that would allow it to enter this compartment. This means that RNA cannot integrate into the DNA of the vaccinated cell.

There is no risk of long-term genetic changes with mRNA vaccines.

The mRNA COVID-19 vaccines by Pfizer and Moderna have undergone safety testing in human clinical trials.

The United States Food and Drug Administration (FDA) have granted Emergency Use Authorization (EUA) for the Pfizer mRNA vaccine after reviewing the safety data from over 37,000 trial participants.

“The most commonly reported side effects, which typically lasted several days, were pain at the injection site, tiredness, headache, muscle pain, chills, joint pain, and fever,” the FDA wrote in their statement. “Of note, more people experienced these side effects after the second dose than after the first dose, so it is important for vaccination providers and recipients to expect that there may be some side effects after either dose, but even more so after the second dose.”

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