(Note: If you wish, first read How mRNA vaccines work (Easy) for simpler English and easier science.)
The Pfizer/BioNTech and Moderna vaccines use messenger RNA (mRNA) technology. Although mRNA vaccines represent a relatively new approach to vaccination, the underlying technology has long been understood by researchers—even though it had not previously been used for large-scale vaccine manufacturing. Messenger RNA is a long RNA molecule that carries genetic instructions within cells. All known cellular organisms utilize both DNA and RNA—DNA stores genetic information, and RNA plays various roles in gene expression—whereas viruses (which are generally not considered living organisms) contain either DNA or RNA.
SARS-CoV-2, the virus that causes COVID-19, is an RNA virus. It infects human cells by attaching to their surfaces and then releasing its own RNA into the cell.
Once inside, the viral RNA moves to ribosomes—tiny cellular machines that normally read messenger RNA (mRNA) to produce the proteins our cells need. However, the virus hijacks these ribosomes to manufacture its own proteins, which are essential for building new copies of the virus.
In a healthy cell, mRNA carries a copy of the genetic information from DNA (located in the nucleus) to the ribosomes. This process is vital for synthesizing the proteins required for building and repairing our bodies using the genetic instructions in the genes inherited from our parents.
By taking over the ribosomes, SARS-CoV-2 ensures that the cell produces the viral proteins necessary to assemble new virus particles, allowing the infection to spread.
Antibodies are Y-shaped proteins that play a crucial role in the immune system. They attach to invading viruses in a way that physically blocks the viral components responsible for binding to the cell membrane—the outer surface of human cells. This action prevents the virus from attaching to the cell and inserting its RNA.
Think of it like gumming up a key so that it can no longer fit into a lock, rendering it unable to open a door.
These antibodies can remain in the body for varying lengths of time, depending on their specific type. Their continued presence provides protection against future infections by the same virus or intruder, enabling the immune system to respond more quickly to identify and neutralize a pathogen if it is encountered again.
An mRNA vaccine is delivered into the body via injection. The mRNA is encased in a lipid nanoparticle—a small, fatty envelope—that helps it cross the cell cell membranes of human dendritic cells (a type of immune cell). Once inside these cells, the mRNA directs the ribosomes (the cell’s protein factories) to produce proteins according to its instructions, much like how a virus operates.
In the case of this vaccine, the mRNA only contains the instructions to make the spike protein—the component of the virus that acts like a key to unlock and enter human cells. The newly produced spike proteins are either displayed directly on the cell surface or released and then captured by the same cell or nearby dendritic cells, which subsequently present them on their surfaces.
Once these spike proteins are on display, T cells (another type of immune cell) recognize them as foreign invaders. This recognition triggers the production of antibodies that specifically bind to the spike protein. In future encounters with the actual SARS-CoV-2 virus, these antibodies can attach to its spike protein, effectively neutralizing the virus and preventing it from infecting cells.
In this way, the immune system is trained to recognize and combat the virus using only the spike protein—a small part of the virus that, by itself, does not cause disease.
One added advantage of producing the spike protein antigen within dendritic cells is that it activates an additional immune pathway.
When dendritic cells display the spike protein on their surface, they help train killer T cell (cytotoxic T lymphocytes). These T cells provide cell-mediated immunity, which works independently of antibody production, further strengthening the body’s defense against the virus.
The mRNA delivered by the vaccine is short-lived and does not enter the cell nucleus, where our DNA is stored. For this and other reasons it is incapable of altering our genetic material—a point often misrepresented by online misinformation.
Within days, after serving its purpose in directing the production of spike proteins, the mRNA is naturally broken down. Like any messenger RNA in a human cell, its components are recycled, ensuring that it does not persist in the body.
In summary, this vaccine is designed to introduce only a small portion of the virus’s genetic code into the body. This limited genetic material provides the instructions to produce the spike protein—a key component of the virus. Once produced, the immune system responds by generating antibodies and establishing a memory of the spike. This immune memory enables the body to quickly recognize and neutralize SARS-CoV-2 if it is encountered again, helping to prevent the virus from spreading.
©2021 Dr. Michael Herrera
To learn more about the structure of the SARS-CoV-2 virus and how it replicates, please read What we knew about the structure of SARS-CoV-2.
For more information on mRNA:
Scitable: Translation: DNA to mRNA to Protein
For more information on mRNA vaccines:
CDC: Understanding mRNA COVID-19 Vaccines
(moved or removed)
BioNTech: mRNA vaccines to address the COVID-19 pandemic
(English page might have been removed)
c&en: Without these lipid shells, there would be no mRNA vaccines for COVID-19
(March 6, 2021)
ACEP: How the COVID-19 mRNA Vaccines Work, and Some Current Concerns
(February 19, 2021)
Yale News: Understanding COVID-19: how mRNA vaccines work (VIDEO)
(January 26, 2021)
Science: mRNA Vaccines: What Happens (January 21, 2021)
NYT: Cómo funciona la vacuna de Pfizer-BioNTech (in Spanish) (January 21, 2021)
Stanford Medicine: How do the new COVID-19 vaccines work? (December 22, 2020)
Harvard Health Publishing: Why are mRNA vaccines so exciting? (December 18, 2020)
MNT: How do mRNA vaccines work? (December 18, 2020)
DNA Science: The First COVID-19 Vaccines: What’s mRNA Got To Do With It?
(December 17, 2020)
McGill: The Vaccine is Here But So Is The Fear (December 15, 2020)
CAS: Meet the mRNA vaccine rookies aiming to take down COVID-19
(December 4, 2020)
(moved or removed)