How adenovirus vaccines work
Adenoviruses are a large family of viruses that can cause a range of illness in people and animals. In people, these viruses can cause relatively mild illness such as colds and pink eye or more serious issues such as diarrhea and pneumonia.
For decades, scientists have been experimenting with adenoviruses and turning them into vehicles or vectors to send information to cells in the body so that the cells can help the immune system recognize certain germs (other than adenoviruses) and attack them. In effect, these efforts with modified adenoviruses have turned them into vaccines.
To do this, scientists first remove the part of the adenovirus’ genetic information that causes harm. They then insert instructions for making viral proteins of the germ they will need to vaccinate against. A dose of vaccine using adenoviruses usually contains many millions or even billions of modified adenoviruses. The vaccine is injected into the muscles of the upper arm. After injection, the modified adenovirus reaches muscle cells and enters them, where it releases its cargo. This cargo consists of instructions for making viral proteins chosen by scientists.
The cells’ machinery “reads” the instructions carried by the adenovirus. As a result, the cells begin to produce the proteins mentioned in the instructions. In this case, the proteins are tiny pieces of SARS-CoV-2.
The muscle cells release the proteins into circulation, where cells of the immune system encounter the proteins. The cells of the immune system recognize the proteins as foreign and a process that we describe next is then triggered.
The cells of the immune system capture the proteins and migrate to nearby lymph nodes. Once inside the lymph nodes, the cells that have captured the viral proteins teach other cells of the immune system to recognize the proteins as foreign and to respond in different ways when they encounter the proteins in the future. For instance, a group of the immune system’s cells called B-cells begins to make antibodies against the viral proteins.
Another group of the immune system’s cells called T-cells learns to attack and destroy the virus and cells that it has infected.
B- and T-cells that have been stimulated by vaccination make many millions, perhaps billions, of copies of themselves and leave the lymph nodes to circulate in the body. Over time, the levels of B- and T-cells in circulation that can recognize the virus fall to low levels. However, a small portion of these cells transform into memory B- and T-cells. These memory cells can live many years and retain the memory of how to defend the body from SARS-CoV-2. These cells reside in lymph nodes and organs of the immune system such as the spleen. Should infection with SARS-CoV-2 occur in the future, once these cells encounter the virus, they become activated and spring into action, making millions of copies of themselves, and contain the virus.
The immunological events described above are a simplified and idealized scenario. SARS-CoV-2 is new to science and it is plausible that sometime after vaccination—perhaps a year or two later—a booster shot may be needed to help people maintain high levels of immunity to SARS-CoV-2.
It is also possible, likely even, that entirely different vaccines may be needed in the future, as SARS-CoV-2 is mutating.
—Sean R. Hosein
REFERENCES:
- Mercado NB, Zahn R, Wegmann F, et al. Single-shot Ad26 vaccine protects against SARS-CoV-2 in rhesus macaques. Nature. 2020 Oct;586(7830):583-588.
- Sadoff J, Le Gars M, Shukarev G, et al. Interim results of a phase 1-2a trial of Ad26 COV2 S Covid-19 vaccine. New England Journal of Medicine. 2021; in press.
- Custers J, Kim D, Leyssen M, et al. Vaccines based on replication incompetent Ad26 viral vectors: Standardized template with key considerations for a risk/benefit assessment. Vaccine. 2021; in press.
- Kremer EJ. Pros and cons of adenovirus-based SARS-CoV-2 vaccines. Molecular Therapy. 2020 Nov 4;28(11):2303-2304.
- Bos R, Rutten L, van der Lubbe JEM, et al. Ad26 vector-based COVID-19 vaccine encoding a prefusion-stabilized SARS-CoV-2 spike immunogen induces potent humoral and cellular immune responses. NPJ Vaccines. 2020 Sep 28;5:91.