How Do the mRNA Vaccines of Pfizer and Moderna Work?
Updated: Feb 28, 2021
The first two COVID-19 vaccines that finished clinical trials and were cleared for use in multiple countries were the Pfizer-BioNTech and Moderna vaccines. Both these vaccines use mRNA.
What is mRNA?
The m in mRNA stands for messenger, and RNA is an abbreviation for ribonucleic acid. The mRNA is a code for the cell to produce a protein. This is similar to an instruction manual on how to create a protein. A small cell component, the ribosome, produces the protein based on the mRNA.
What is the mRNA in these vaccines used for?
The mRNA from the Moderna and Pfizer vaccines is used as a set of instructions to produce the spike (S) protein from the virus.
The coronavirus is an enveloped virus. The envelope serves as the ‘coat’ of the virus. This means that the virus is packaged in an outer layer of oily lipid molecules. In between these lipid molecules, the coat has some proteins. One of these proteins in the coating is used for the vaccine: the spike (S) protein (see Figure). The spike protein is important as the virus needs it to bind to specific components on human cells. This binding allows the virus to enter and infect the cell. Blocking this protein can therefore stop the virus from infecting more cells and spreading in the body.
How do the mRNA vaccines trigger an immune response against the virus?
When you are vaccinated, the mRNA that is injected into your body is taken up by some cells in your body, that will use it to produce lots of S protein. The S protein will be placed on the coating of these cells as a form of signal that your immune system can recognize and use (see also post on the immune response).
The immune system then comes into action in two ways:
Your B cells will start producing antibodies against the spike protein. The antibodies will bind to any spike protein it comes in contact with, blocking any future virus you may encounter from being able to bind your cells and infect the cells.
T cells will be trained to recognize S protein fragments (also called antigens). In the future, if you get infected with the virus, your cells will show these fragments to your T cells. In that way, the trained T cells can recognize the cells that are infected. The T cells will kill these infected cells, which stops the virus’s further spread in your body.
What else is in the vaccine?
mRNA is a very fragile molecule and is easily broken down in the body. Because of this, in the vaccine, the mRNA is surrounded by an oily substance. This substance forms a little bubble around it that protects it from destruction. This oily bubble also helps it enter your cells, in which it is released and can be translated into protein by your cell. The mRNA is quickly broken down by the cell, so the protein production is only temporary. No components of the vaccine will be left in your body.
Good to know
Since the mRNA breaks down easily at room temperature, the vaccines have to be stored at very low temperatures (-70C). This is to maintain the quality of the mRNA. Before injection in your arm, the vaccine is thawed. It has been tested that this short period of being at room temperature will not affect the vaccine’s quality.
The main difference between the Moderna and Pfizer vaccines is the exact mRNA code that is used and the formulation of the oily substance surrounding it.
It is important to note that the spike protein is not the virus itself, which means that it is impossible to get COVID-19 from the vaccine or the spike protein alone.
Polack et al. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. NEJM 2020 https://www.nejm.org/doi/full/10.1056/NEJMoa2034577
Baden et al. Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. NEJM 2021 https://www.nejm.org/doi/full/10.1056/NEJMoa2035389
Pfizer FDA documentation: https://www.fda.gov/media/144246/download
Moderna FDA documentation: https://www.fda.gov/media/144434/download
Contributed by: Text: Maartje Wouters, Illustration: Armando Andres Roca Suarez