How the Oxford-AstraZeneca Vaccine Works

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How the Oxford-AstraZeneca Vaccine Works

Oxford University, in collaboration with the British-Swedish company AstraZeneca, has developed and tested a coronavirus vaccine known as ChAdOx1 nCoV-19 or AZD1222. A clinical study found that the vaccine was 90 percent effective, depending on the starting dose. However, uncertainty about the results has clouded the outlook.

A piece of the coronavirus

The SARS-CoV-2 virus is filled 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' genetic instructions to build the spike protein. Unlike the Pfizer-BioNTech and Moderna vaccines, which store instructions in single-stranded RNA, the Oxford vaccine uses double-stranded DNA.

DNA in an adenovirus

The researchers added the gene for the coronavirus spike protein to another virus called 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 penetrate cells but not replicate in them.

AZD1222 comes from decades of research into adenovirus-based vaccines. In July the first was approved for general use – an Ebola vaccine from Johnson & Johnson. Advanced clinical trials for other diseases including H.I.V. and Zika.

The Oxford-AstraZeneca vaccine against Covid-19 is more robust than the mRNA vaccines from Pfizer and Moderna. DNA isn't as fragile as RNA, and the adenovirus' hard protein shell protects the genetic material inside. Therefore, the Oxford vaccine does not need to be frozen. The vaccine is expected to last at least six months when refrigerated at 2 to 8 degrees Celsius.

Enter a cell

After the vaccine is injected into a person's arm, the adenoviruses bump into cells and cling to proteins on their surface. The cell swallows the virus into a bubble and pulls it inside. Inside, the adenovirus escapes from the bladder and migrates to the nucleus, the chamber in which the cell's DNA is stored.

Virus devoured

in a bubble

Virus devoured

in a bubble

Virus devoured

in a bubble

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

Structure of spike proteins

The mRNA leaves the nucleus and the cell's molecules read their sequence and start building spike proteins.

Three spines

Proteins combine

spikes

and protein

Fragments

Show

Spike protein

Fragments

Three spines

Proteins combine

spikes

and protein

Fragments

Show

Spike protein

Fragments

Three spines

Proteins combine

spikes

and protein

Fragments

Show

Spike protein

Fragments

Three spines

Proteins combine

spikes

and protein

Fragments

Show

Spike protein

Fragments

Three spines

Proteins combine

spikes

and protein

Fragments

Show

Spike protein

Fragments

Three spines

Proteins combine

spikes

and protein

Fragments

Show

Spike protein

Fragments

Three spines

Proteins combine

spikes

and protein

Fragments

Show

Spike protein

Fragments

Some of the spike proteins produced by the cell form spikes that migrate to its surface and their tips stick out. The vaccinated cells also break down into fragments some of the proteins that 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 turning on the cell's alarm systems. The cell sends out warning signals to activate nearby immune cells. By triggering this alarm, the Oxford-AstraZeneca vaccine makes the immune system more responsive to the spike proteins.

Discover 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.

Present a

Spike protein

fragment

Present a

Spike protein

fragment

Present a

Spike protein

fragment

The cell presents fragments of the spike protein on its surface. When other cells called helper T cells recognize these fragments, the helper T cells can set off the alarm and help other immune cells fight the infection.

Make antibodies

Other immune cells, called B cells, can encounter the coronavirus spikes and protein fragments on the surface of vaccinated cells. Some of the B cells may be able to bind to the spike proteins. When these B cells are then activated by helper T cells, they start to multiply and pour out antibodies that target the spike protein.

Matching

Surface proteins

Matching

Surface proteins

Matching

Surface proteins

Matching

Surface proteins

Matching

Surface proteins

Matching

Surface proteins

Matching

surface

Proteins

Matching

surface

Proteins

Matching

surface

Proteins

Matching

Surface proteins

Matching

Surface proteins

Matching

Surface proteins

Stop the virus

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

Kill infected cells

The 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 have the spike protein fragments on their surfaces.

Present a

Spike protein

fragment

Beginning

to kill them

infected cell

Present a

Spike protein

fragment

Beginning

to kill them

infected cell

Present a

Spike protein

fragment

Beginning

to kill them

infected cell

Present a

Spike protein

fragment

I'm starting to kill

the infected cell

Present a

Spike protein

fragment

I'm starting to kill

the infected cell

Present a

Spike protein

fragment

I'm starting to kill

the infected cell

Present a

Spike protein

fragment

I'm starting to kill

the infected cell

Present a

Spike protein

fragment

I'm starting to kill

the infected cell

Present a

Spike protein

fragment

I'm starting to kill

the infected cell

Present a

Spike protein

fragment

I'm starting to kill

the infected cell

Present a

Spike protein

fragment

I'm starting to kill

the infected cell

Present a

Spike protein

fragment

I'm starting to kill

the infected cell

Memory of the virus

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

Surprisingly, the vaccine combination, where the first dose was only half the strength, was 90 percent effective in preventing Covid-19 in the clinical trial. In contrast, the combination of two full-dose shots resulted in only 62 percent effectiveness. The researchers speculate that the lower first dose better mimics the experience of infection and promotes a stronger immune response when the second dose is given.

Second dose

28 days later

Second dose

28 days later

Second dose

28 days later

Because the vaccine is so new, researchers don't know how long it might last to protect. It is possible that the number of antibodies and killer T cells may decrease in the months after the vaccination. However, the immune system also contains special cells, so-called memory B cells and memory T cells, which can store information about the coronavirus for years or even decades.

For more information on the vaccine, see AstraZeneca's Covid Vaccine: What You Need To Know.

Vaccination timeline

January 2020 Researchers at Oxford University's Jenner Institute begin work on a coronavirus vaccine.

27th of March Oxford researchers begin screening volunteers for a human experiment.

April 23 Oxford is starting a phase 1/2 study in the UK.

A vial of the Oxford AstraZeneca vaccine.John Cairns / Oxford University / Agence France-Presse

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

May 21 The U.S. government is pledging up to $ 1.2 billion to fund AstraZeneca development and manufacturing of the vaccine.

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

23rd June A phase 3 study is starting in Brazil.

June 28th A phase 1/2 study is starting in South Africa.

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

18th of August A phase 3 study with the vaccine is starting in the USA with 40,000 participants.

September 6th After a suspected side effect of a British volunteer, human trials are exposed around the world. Neither AstraZeneca nor Oxford announce the break.

September 8th The news of interrupted legal proceedings will be published.

12th September The clinical trial will continue in the UK but will continue to be paused in the US.

A syringe of the vaccine at a trial site in the UK.Andrew Testa for the New York Times

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

November 23 AstraZeneca announces clinical trial data showing that an initial half dose of the vaccine appears more effective than a full dose. However, irregularities and omissions raise many questions about the results.

British Prime Minister Boris Johnson holds a vial of the vaccine in his hand.Pool photo by Paul Ellis

December 7th The Serum Institute of India announces that it has applied for emergency approval from the Government of India to use the vaccine known in India as Covishield.

December 8th Oxford and AstraZeneca publish the first scientific paper on a phase 3 clinical study with a coronavirus vaccine.

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

2021 The company expects to produce up to two billion cans over the next year. Each person vaccinated will require two doses at an expected cost of $ 3 to $ 4 per dose.


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

Chasing the coronavirus

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