How the Oxford-AstraZeneca Vaccine Works
Oxford University has partnered with Anglo-Swedish company AstraZeneca to develop and test a coronavirus vaccine called 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 loaded 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. The first was approved for general use in July – 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 begin 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, researchers inadvertently gave some volunteers only half a dose.
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 will decrease in the months after vaccination. The immune system also contains special cells, so-called storage B cells and storage 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 schedule
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 US government is pledging up to $ 1.2 billion to fund AstraZeneca development and manufacture of the vaccine.
28th of May A phase 2/3 study with 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 suspended 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 has released 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.
Prime Minister Boris Johnson of Great Britain holds a vaccine vial 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.
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