Unlike many other vaccines that contain an infectious pathogen or a part of it, viral vector vaccines use a harmless virus to deliver a piece of genetic code to our cells, allowing them to make a pathogen’s protein. This trains our immune system to react to future infections.
When we have a bacterial or viral infection, our immune system reacts to molecules from the pathogen. If it is our first encounter with the invader, a finely tuned cascade of processes come together to fight the pathogen and build up immunity for future encounters.
Many traditional vaccines deliver an infectious pathogen or a part of it to our bodies to train our immune system to fight off future exposures to the pathogen.
Viral vector vaccines work differently. They make use of a harmless virus to deliver a piece of genetic code from a pathogen to our cells to mimic an infection. The harmless virus acts as a delivery system, or vector, for the genetic sequence.
Our cells then make the viral or bacterial protein that the vector has delivered and present it to our immune system.
This allows us to develop a specific immune response against a pathogen without the need to have an infection.
However, the viral vector itself plays an additional role by boosting our immune response. This leads to a more robust reaction than if the pathogen’s genetic sequence was delivered on its own.
The Oxford-AstraZeneca COVID-19 vaccine uses a chimpanzee common cold viral vector known as ChAdOx1, which delivers the code that allows our cells to make the SARS-CoV-2 spike protein.
Scientists have studied many different types of viral vectors, including adenoviral vectors. Adenoviruses can cause the common cold, and there are many different types of these viruses.
Originally, researchers worked with modified adenoviruses for the purpose of gene therapy. However, because they are able to stimulate our immune system, adenoviral vectors make good candidates for vaccine development.
The Oxford-AstraZeneca COVID-19 vaccine uses a chimpanzee adenoviral vector. It delivers the gene that encodes the SARS-CoV-2 spike protein to our cells.
Our cells then transcribe this gene into messenger RNA, or mRNA, which in turn prompts our cellular machine to make the spike protein in the main body, or the cytoplasm, of the cell.
Then our cells present the spike protein, as well as small parts of it, on the cell surface, prompting our immune system to make antibodies and mount T cell responses.
The ChAdOx1 viral vector in the Oxford-AstraZeneca COVID-19 vaccine has been genetically altered so that it cannot replicate. Therefore, it is unable to cause an adenovirus infection in people who have had the vaccine.
It also cannot cause COVID-19, as it does not carry enough of the SARS-CoV-2 genetic material for our cells to assemble the entire SARS-CoV-2 virus. It only carries the code to make the spike protein.
With all viral vectors, one issue to consider is preexisting immunity. If a person encountered the virus that serves as the vector in the past, they may have antibodies to the virus. This means that their body will try to fight and destroy the viral vector, potentially making a vaccine less effective.
The Oxford University research team behind the Oxford-AstraZeneca COVID-19 vaccine previously reported that levels of preexisting antibodies to the ChAdOx1 viral vector were low when they assessed this in samples from adults from the United Kingdom and Gambia.
Writing in Nature Medicine in December 2020, the researchers saw no correlation between immunity to the vector and how well the COVID-19 vaccine worked or whether the volunteers receiving it had side effects in a Phase 1/2 clinical trial.
Other COVID-19 vaccines that use viral vectors include the Russian Sputnik V vaccine and the Janssen single-dose vaccine candidate.