How the Oxford-AstraZeneca vaccine works

The University of Oxford has collaborated with the British-Swedish company AstraZeneca to develop and test a coronavirus vaccine known as ChAdOx1 nCoV-19 or AZD1222. A clinical study showed that the vaccine was up to 90% effective, depending on the initial dose. But uncertainty over the results has darkened its prospects.

A piece of coronavirus

The SARS-CoV-2 virus is adorned with proteins that it uses to enter human cells. These so-called spike proteins are 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 instructions in single-stranded RNA, the Oxford vaccine uses double-stranded DNA.

DNA inside an adenovirus

The researchers added the coronavirus spike protein gene to another virus called adenovirus. Adenoviruses are common viruses that usually 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 cannot replicate inside them.

AZD1222 is the result of decades of research into adenovirus vaccines. In July, the first was approved for general use – a vaccine for Ebola, developed by Johnson & Johnson. Advanced clinical trials are underway for other diseases, including HIV and Zika.

The Oxford-AstraZeneca vaccine for Covid-19 is more robust than the mRNA vaccines from Pfizer and Moderna. DNA is not as fragile as RNA, and the hard protein layer of the adenovirus helps protect the genetic material inside. As a result, the Oxford vaccine should not remain frozen. The vaccine is expected to last at least six months when refrigerated at 2-8 ° C (38-46 ° F).

Entering a cell

After injecting the vaccine into a person’s arm, the adenoviruses hit the cells and attach to the proteins on their surface. The cell swallows the virus in a bubble and pulls it inside. Once inside, the adenovirus escapes the bubble and moves to the nucleus, the room where the cell’s DNA is stored.

The adenovirus pushes its DNA into the nucleus. The adenovirus is designed so that it cannot make copies on its own, but the coronavirus spike protein gene 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 to assemble the spike proteins.

Some of the peak proteins produced by the cell form peaks that migrate to its surface and detach their peaks. Vaccinated cells also break down some proteins into fragments, which they present on their surface. These prominent peaks and peak protein fragments can then be recognized by the immune system.

Adenovirus also triggers the immune system by triggering cell alarm systems. The cell sends warning signals to activate nearby immune cells. By triggering this alarm, the Oxford-AstraZeneca vaccine makes the immune system react more strongly to spike proteins.

Seeing the intruder

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

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

Manufacture of antibodies

Other immune cells, called B cells, can collide with the tips of the coronavirus on the surface of vaccinated cells or with fragments of free floating proteins. Some of the B cells may be able to bind to the peak proteins. If these B cells are then activated by helper T cells, they will begin to proliferate and shed antibodies targeting the spike protein.

Stopping the virus

Antibodies can attach to the tips of the coronavirus, mark the virus for destruction, and prevent infection by blocking the attachment of the tips to other cells.

Killing infected cells

Antigen-presenting cells can also activate another type of immune cell called a killer T cell to search for and destroy any coronavirus-infected cells that display fragments of spike proteins on their surfaces.

Reminding us of the virus

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

Surprisingly, the combination of vaccines in which the first dose was only half the concentration was 90% effective in preventing Covid-19 in the clinical trial. In contrast, the combination of two full-dose photographs resulted in an efficacy of only 62%. The researchers speculate that the lower dose did a better job of mimicking the experience of an infection, promoting a stronger immune response when the second dose was given.

Because the vaccine is so new, researchers do not know how long its protection could last. The number of killer antibodies and T cells may decrease in the months after vaccination. But the immune system also contains special cells called memory B cells and memory T cells that could hold information about the coronavirus for years or even decades.

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

Vaccine timeline

January 2020 Researchers at the Jenner Institute at Oxford University are beginning work on a coronavirus vaccine.

March 27 Oxford researchers are beginning to test volunteers for a human process.

April 23 Oxford begins a 1/2 phase process in the UK.

April 30 Oxford is partnering with AstraZeneca to develop, manufacture and distribute the vaccine.

21 May The US government is committing up to $ 1.2 billion to help fund the development and manufacture of the vaccine by AstraZeneca.

May 28 A 2/3 phase study of the vaccine is starting in the UK. Some of the volunteers accidentally receive half of the prescribed dose.

June 23 A phase 3 process begins in Brazil.

June 28 A phase 1/2 study begins in South Africa.

July 30 A paper from Nature shows that the vaccine seems safe in animals and seems to prevent pneumonia.

August 18 A phase 3 study of the vaccine begins in the United States, with 40,000 participants.

September 6 Trials in humans are suspended worldwide after a suspected adverse reaction to a British volunteer. Neither AstraZeneca nor Oxford announce the break.

September 8 News of the interrupted trials becomes public.

September 12 The clinical trial resumes in the United Kingdom, but remains discontinued in the United States.

October 23 Following the investigation, the Food and Drug Administration allows the Phase 3 clinical trial to continue in the United States.

November 23 AstraZeneca announces data from clinical trials showing that half an initial dose of vaccine seems more effective than a full dose. But irregularities and omissions raise many questions about the results.

December 7 Serum Institute of India announces that it had applied to the Indian Government for emergency use of the vaccine, known as Covishield in India.

December 8 Oxford and AstraZeneca publish the first scientific paper on a phase 3 clinical trial of a coronavirus vaccine.

December 11th AstraZeneca announces that it will collaborate with the Russian creators of the Sputnik V vaccine, which is also made from adenoviruses.

2021 The company expects to produce up to two billion doses next year. Each vaccinated person will need two doses, at an estimated price of $ 3 to $ 4 per dose.

Sources: National Center for Biotechnology Information; The nature; Lynda Coughlan, University of Maryland School of Medicine.

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