How the Oxford-AstraZeneca Vaccine Works

The University of Oxford partnered with the British-Swedish company AstraZeneca to develop and test a coronavirus vaccineknown as ChAdOx1 nCoV-19 or AZD1222. A large clinical trial showed the vaccine offered strong protection, with an overall efficacy of 76 percent.

Dozens of countries have authorized the vaccine for emergency use, but it is not yet authorized by the Food and Drug Administration.

A Piece of the Coronavirus

The SARS-CoV-2 virus is studded with proteins that it uses to enter human cells. These so-called spike proteins make a tempting target for potential vaccines and treatments.

The Oxford-AstraZeneca vaccine is based on the virus’s genetic instructions for building the spike protein. But unlike the Pfizer-BioNTech and Moderna vaccines, which store the instructions in single-stranded RNA, the Oxford vaccine uses double-stranded DNA.

DNA Inside an Adenovirus

The researchers added the gene for the coronavirus spike protein to another virus called an adenovirus. Adenoviruses are common viruses that typically cause colds or flu-like symptoms. The Oxford-AstraZeneca team used a modified version of a chimpanzee adenovirus, known as ChAdOx1. It can enter cells, but it can’t replicate inside them.

AZD1222 comes out of decades of research on adenovirus-based vaccines. In July, the first one was approved for general use — a vaccine for Ebola, made by Johnson & Johnson. Advanced clinical trials are underway for other diseases, including H.I.V. and Zika.

The Oxford-AstraZeneca vaccine for Covid-19 is more rugged than the mRNA vaccines from Pfizer and Moderna. DNA is not as fragile as RNA, and the adenovirus’s tough protein coat helps protect the genetic material inside. As a result, the Oxford vaccine doesn’t have to stay frozen. The vaccine is expected to last for at least six months when refrigerated at 38–46°F (2–8°C).

Entering a Cell

After the vaccine is injected into a person’s arm, the adenoviruses bump into cells and latch onto proteins on their surface. The cell engulfs the virus in a bubble and pulls it inside. Once inside, the adenovirus escapes from the bubble and travels to the nucleus, the chamber where the cell’s DNA is stored.

The adenovirus pushes its DNA into the nucleus. The adenovirus is engineered so it can’t make copies of itself, but the gene for the coronavirus spike protein can be read by the cell and copied into a molecule called messenger RNA, or mRNA.

Building Spike Proteins

The mRNA leaves the nucleus, and the cell’s molecules read its sequence and begin assembling spike proteins.

Some of the spike proteins produced by the cell form spikes that migrate to its surface and stick out their tips. The vaccinated cells also break up some of the proteins into fragments, which they present on their surface. These protruding spikes and spike protein fragments can then be recognized by the immune system.

The adenovirus also provokes the immune system by switching on the cell’s alarm systems. The cell sends out warning signals to activate immune cells nearby. By raising this alarm, the Oxford-AstraZeneca vaccine causes the immune system to react more strongly to the spike proteins.

Spotting the Intruder

When a vaccinated cell dies, the debris contains spike proteins and protein fragments that can then be taken up by a type of immune cell called an antigen-presenting cell.

The cell presents fragments of the spike protein on its surface. When other cells called helper T cells detect these fragments, the helper T cells can raise the alarm and help marshal other immune cells to fight the infection.

Making Antibodies

Other immune cells, called B cells, may bump into the coronavirus spikes on the surface of vaccinated cells, or free-floating spike protein fragments. A few of the B cells may be able to lock onto the spike proteins. If these B cells are then activated by helper T cells, they will start to proliferate and pour out antibodies that target the spike protein.

Stopping the Virus

The antibodies can latch onto coronavirus spikes, mark the virus for destruction and prevent infection by blocking the spikes from attaching to other cells.

Killing Infected Cells

The antigen-presenting cells can also activate another type of immune cell called a killer T cell to seek out and destroy any coronavirus-infected cells that display the spike protein fragments on their surfaces.

Remembering the Virus

The Oxford-AstraZeneca vaccine requires two doses, given four weeks apart, to prime the immune system to fight off the coronavirus. During the clinical trial of the vaccine, the researchers unwittingly gave some volunteers only half a dose.

Surprisingly, the vaccine combination in which the first dose was only half strength was 90 percent effective at preventing Covid-19 in the clinical trial. In contrast, the combination of two full-dose shots led to just 62 percent efficacy. The researchers speculate that the lower first dose did a better job of mimicking the experience of an infection, promoting a stronger immune response when the second dose was administered.

Because the vaccine is so new, researchers don’t know how long its protection might last. It’s possible that in the months after vaccination, the number of antibodies and killer T cells will drop. But the immune system also contains special cells called memory B cells and memory T cells that might retain information about the coronavirus for years or even decades.

For more about the vaccine, see AstraZeneca’s Covid Vaccine: What You Need to Know.