Newer vaccines such as mRNA vaccines and viral vectored vaccines, including the Oxford ChAdOx1 nCoV-19 vaccine differ from many traditional vaccines in the way they activate the immune system. Most traditional vaccines inject the antigen (part of the disease that stimulates an immune response) directly into the body. See types of vaccine for information about how different types of vaccines work.
In contrast, these two newer approaches deliver the genetic instructions for the antigen to the body’s cells. The cells then manufacture the antigen which goes on to stimulate the immune response. Injecting genetic material has raised questions about the use of these vaccines, such as whether they can modify the DNA of those receiving them. Here, we will explain why this is not possible.
Click here for an accessible text version of this infographic
Firstly, we will look at how cells normally manufacture proteins. Our DNA (DeoxyRibonucleic Acid) is safely packaged inside the nucleus of a cell and cannot leave. Within this DNA are gene sequences, and each gene encodes the blueprints for making one of the proteins the body needs. To make a protein the first step is to transcribe DNA into mRNA (messenger Ribonucleic Acid) using a special enzyme (or “tool”) called RNA polymerase. This step is a one-way process as cells are unable to transcribe RNA back into DNA.
Unlike DNA, mRNA is free to leave the nucleus as it has a pass that allows it to exit. However, this pass is one way and once it leaves, the mRNA cannot return. Once it has left the nucleus the mRNA links up with the special cellular machinery in the cytoplasm. This machinery uses the information coded in the mRNA to make new proteins. As with the process of going from DNA to mRNA this process is also one-way, and it’s not possible to go backwards from protein to mRNA. These proteins may be used inside the cell or transported out of the cell for use elsewhere in the body.
The COVID-19 mRNA vaccines take advantage of this internal process to make copies of the spike protein, which usually appears on the surface of the coronavirus. There are two types of vaccine which use this process:
In this type of vaccine, mRNA is delivered to the cell inside a lipid membrane. Once the mRNA is inside the cell, the same machinery that is used to make our own proteins can make the spike protein. This mRNA has no way of getting into the nucleus where our DNA is. Even if it could, mRNA cannot fuse with DNA and as with our own mRNA, has no way of getting translated back to DNA. As such, there is no way for human DNA to be altered by an mRNA vaccine. This mRNA lasts a few days before the cell removes it, but in that time we have produced a lot of spike protein to stimulate the immune response.
Viral vectored vaccines
Viral vectored vaccines work in a different way. The genetic information inside a viral vectored vaccine like ChAdOx1 is DNA rather than RNA. This DNA is a short linear piece of double stranded DNA which contains the viral genes along with the gene for the spike protein. The viral vector first infects the cell and then delivers this DNA to the cell nucleus. The cell can then transcribe the viral genes (DNA) into mRNA using the same RNA polymerase it uses for our own genes. After transcription, the mRNA gets tagged so it can leave the nucleus and be made into spike protein by the cell machinery.
In the Oxford vaccine, the viral gene that is required to replicate viral DNA has been removed. As viruses use a different process to human cells to replicate their DNA, the cell itself cannot replicate viral DNA either. This means the viral vector cannot replicate (make more viruses) or cause disease. Both the original viral DNA and the spike protein mRNA only last a few days before the cell removes them. Such design features alongside a cell’s natural DNA protection measures, prevents any possibility of viral DNA integrating with human DNA.
For more information about the new types of COVID-19 vaccines, see The Race for Coronavirus Vaccines.