How the Oxford-AstraZeneca vaccine works

The University of Oxford has partnered with Anglo-Swedish company AstraZeneca to develop and test a vaccine against the coronavirus known as ChAdOx1 nCoV-19 or AZD1222. A clinical trial found the vaccine to be up to 90% effective, depending on the initial dose. But uncertainty about the results clouded his outlook.

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 are a tempting target for potential vaccines and treatments.

The Oxford-AstraZeneca vaccine is based on the virus’s genetic instructions to build 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 it cannot replicate inside.

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

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 tough protein layer of the adenovirus helps protect the genetic material inside. As a result, the Oxford vaccine does not have to stay frozen. The vaccine should last at least six months when refrigerated between 38 and 46 degrees Fahrenheit (2-8 degrees Celsius).

Enter a cell

After the vaccine is injected into a person’s arm, adenoviruses collide with cells and attach to 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 makes its way to the nucleus, the chamber where the cell’s DNA is stored.

The adenovirus pushes its DNA into the nucleus. The adenovirus is designed so that it cannot reproduce 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.

Build advanced proteins

The mRNA leaves the nucleus, and the cell’s molecules read its sequence and begin to assemble advanced proteins.

Some of the spike proteins produced by the cell form spikes that migrate to its surface and protrude from their ends. Vaccinated cells also break down some of the proteins into fragments, which they present on their surface. These protruding spikes and fragments of spike proteins can then be recognized by the immune system.

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

Spot the intruder

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

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

Make antibodies

Other immune cells, called B cells, can strike coronavirus peaks and protein fragments on the surface of vaccinated cells. Some of the B cells may be able to lock onto spike proteins. If these B cells are then activated by helper T cells, they will start to proliferate and release antibodies that target the spike protein.

Stop the virus

Antibodies can cling to peaks in coronavirus, mark the virus for destruction, and prevent infection by preventing the peaks from attaching to other cells.

Kill infected cells

Antigen presenting cells can also activate another type of immune cell called a killer T cell to find and destroy any cells infected with coronavirus that display the spike protein fragments on their surfaces.

Remember the virus

The Oxford-AstraZeneca vaccine requires two doses, spaced four weeks apart, to allow the immune system to fight against the coronavirus. During the clinical trial of the vaccine, researchers unintentionally gave some volunteers only half a dose.

Surprisingly, the vaccine combination in which the first dose was only half the strength was 90% effective in preventing Covid-19 in the clinical trial. In contrast, the combination of two full-dose injections only led to an efficacy of 62%. Researchers believe that the lower first dose better mimicked the experience of infection, promoting a stronger immune response when the second dose was given.

Because the vaccine is so new, researchers aren’t sure how long its protection might last. It is possible that in the months following vaccination, the number of antibodies and killer T cells may decrease. 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 on the vaccine, see AstraZeneca Covid Vaccine: What you need to know.

Vaccine timeline

January 2020 Researchers at the Jenner Institute at the University of Oxford begin work on a vaccine against the coronavirus.

March 27 Oxford researchers are starting to select volunteers for a human trial.

23 april Oxford is starting a phase 1/2 trial in Great Britain.

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

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

May 28 A phase 2/3 trial of the vaccine begins in Britain. Some volunteers accidentally receive half the intended dose.

23 june Phase 3 trial begins in Brazil.

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

July 30 An article in Nature shows that the vaccine appears safe in animals and appears to prevent pneumonia.

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

Sep 6 Human trials are on hold around the world after a suspected adverse reaction in a British volunteer. Neither AstraZeneca nor Oxford are announcing the break.

Sep 8 News about the suspended trials becomes public.

Sep 12 The clinical trial resumes in the United Kingdom but remains suspended in the United States.

23 october After investigation, the Food and Drug Administration authorizes the continuation of the phase 3 clinical trial in the United States.

23 november AstraZeneca announces clinical trial data which shows that an initial half-dose of the vaccine appears to be more effective than a full dose. But the irregularities and omissions raise many questions about the results.

Dec 7 The Serum Institute of India ad that he asked the Indian government for permission to use the vaccine, known as Covishield, in India for emergency use.

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

Dec 11 AstraZeneca announces that it will collaborate with the Russian creators of the Sputnik V vaccine, also made from adenovirus.

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

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

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