How the Pfizer-BioNTech Vaccine Works

The German company BioNTech partnered with Pfizer to develop and test a coronavirus vaccine known as BNT162b2, the generic name tozinameran or the brand name Comirnaty. A clinical trial demonstrated that the vaccine has an efficacy rate of 95 percent in preventing Covid-19.

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.

Spikes

Spike

protein

gene

Spikes

Spike

protein

gene

CORONAVIRUS

Like the Moderna vaccine, the Pfizer-BioNTech vaccine is based on the virus’s genetic instructions for building the spike protein.

mRNA Inside an Oily Shell

The vaccine uses messenger RNA, genetic material that our cells read to make proteins. The molecule — called mRNA for short — is fragile and would be chopped to pieces by our natural enzymes if it were injected directly into the body. To protect their vaccine, Pfizer and BioNTech wrap the mRNA in oily bubbles made of lipid nanoparticles.

Lipid

nanoparticles

surrounding

mRNA

Lipid nanoparticles

surrounding mRNA

Because of their fragility, the mRNA molecules will quickly fall apart at room temperature. Pfizer is building special containers with dry ice, thermal sensors and GPS trackers to ensure the vaccines can be transported at –94°F (–70°C) to stay viable.

Entering a Cell

After injection, the vaccine particles bump into cells and fuse to them, releasing mRNA. The cell’s molecules read its sequence and build spike proteins. The mRNA from the vaccine is eventually destroyed by the cell, leaving no permanent trace.

VACCINE

PARTICLES

VACCINATED

CELL

Spike

protein

mRNA

Translating mRNA

Three spike

proteins combine

Spike

Cell

nucleus

Spikes

and protein

fragments

Displaying

spike protein

fragments

Protruding

spikes

VACCINE

PARTICLES

VACCINATED

CELL

Spike

protein

mRNA

Translating mRNA

Three spike

proteins combine

Spike

Cell

nucleus

Spikes

and protein

fragments

Displaying

spike protein

fragments

Protruding

spikes

VACCINE

PARTICLES

VACCINATED

CELL

Spike

protein

mRNA

Translating mRNA

Three spike

proteins combine

Spike

Cell

nucleus

Spikes

and protein

fragments

Displaying

spike protein

fragments

Protruding

spikes

VACCINE

PARTICLES

VACCINATED

CELL

Spike

protein

mRNA

Translating mRNA

Three spike

proteins combine

Spike

Cell

nucleus

Spikes

and protein

fragments

Displaying

spike protein

fragments

Protruding

spikes

VACCINE

PARTICLES

VACCINATED

CELL

Spike

protein

mRNA

Translating mRNA

Three spike

proteins combine

Spike

Cell

nucleus

Spikes

and protein

fragments

Displaying

spike protein

fragments

Protruding

spikes

VACCINE

PARTICLES

VACCINATED

CELL

Spike

protein

mRNA

Translating mRNA

Three spike

proteins combine

Spike

Cell

nucleus

Spikes

and protein

fragments

Displaying

spike protein

fragments

Protruding

spikes

VACCINE

PARTICLES

VACCINATED

CELL

Spike

protein

mRNA

Translating mRNA

Three spike

proteins combine

Spike

Cell

nucleus

Spikes

and protein

fragments

Displaying

spike protein

fragments

Protruding

spikes

Some of the spike proteins form spikes that migrate to the surface of the cell 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.

Spotting the Intruder

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

Debris from

a dead cell

ANTIGEN-

PRESENTING

CELL

Engulfing

a spike

Digesting

proteins

Presenting a

spike protein

fragment

HELPER

T CELL

Debris from

a dead cell

ANTIGEN-

PRESENTING

CELL

Engulfing

a spike

Digesting

the proteins

Presenting a

spike protein

fragment

HELPER

T CELL

Debris from

a dead cell

Engulfing

a spike

ANTIGEN-

PRESENTING

CELL

Digesting

the proteins

Presenting a

spike protein

fragment

HELPER

T 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.

HELPER

T CELL

Activating

the B cell

Matching

surface proteins

VACCINATED

CELL

B CELL

SECRETED

ANTIBODIES

HELPER

T CELL

Activating

the B cell

Matching

surface proteins

VACCINATED

CELL

B CELL

SECRETED

ANTIBODIES

HELPER

T CELL

VACCINATED

CELL

Activating

the B cell

Matching

surface proteins

B CELL

SECRETED

ANTIBODIES

HELPER

T CELL

VACCINATED

CELL

Activating

the B cell

Matching

surface proteins

B CELL

SECRETED

ANTIBODIES

HELPER

T CELL

VACCINATED

CELL

Activating

the B cell

Matching

surface proteins

B CELL

SECRETED

ANTIBODIES

HELPER

T CELL

VACCINATED

CELL

Activating

the B cell

Matching

surface proteins

B CELL

SECRETED

ANTIBODIES

HELPER

T CELL

Activating

the B cell

B CELL

Matching

surface

proteins

VACCINATED

CELL

HELPER

T CELL

Activating

the B cell

B CELL

Matching

surface

proteins

VACCINATED

CELL

HELPER

T CELL

Activating

the B cell

B CELL

Matching

surface

proteins

VACCINATED

CELL

HELPER

T CELL

Activating

the B cell

B CELL

Matching

surface proteins

VACCINATED

CELL

HELPER

T CELL

Activating

the B cell

B CELL

Matching

surface proteins

VACCINATED

CELL

HELPER

T CELL

Activating

the B cell

B CELL

Matching

surface proteins

VACCINATED

CELL

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.

ANTIBODIES

VIRUS

ANTIBODIES

VIRUS

ANTIBODIES

VIRUS

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.

ANTIGEN-

PRESENTING

CELL

Presenting a

spike protein

fragment

ACTIVATED

KILLER

T CELL

INFECTED

CELL

Beginning

to kill the

infected cell

ANTIGEN-

PRESENTING

CELL

Presenting a

spike protein

fragment

ACTIVATED

KILLER

T CELL

INFECTED

CELL

Beginning

to kill the

infected cell

ANTIGEN-

PRESENTING

CELL

Presenting a

spike protein

fragment

ACTIVATED

KILLER

T CELL

INFECTED

CELL

Beginning

to kill the

infected cell

ANTIGEN-

PRESENTING

CELL

Presenting a

spike protein

fragment

ACTIVATED

KILLER

T CELL

Beginning to kill

the infected cell

INFECTED

CELL

ANTIGEN-

PRESENTING

CELL

Presenting a

spike protein

fragment

ACTIVATED

KILLER

T CELL

Beginning to kill

the infected cell

INFECTED

CELL

ANTIGEN-

PRESENTING

CELL

Presenting a

spike protein

fragment

ACTIVATED

KILLER

T CELL

Beginning to kill

the infected cell

INFECTED

CELL

ANTIGEN-

PRESENTING

CELL

Presenting a

spike protein

fragment

ACTIVATED

KILLER

T CELL

Beginning to kill

the infected cell

INFECTED

CELL

ANTIGEN-

PRESENTING

CELL

Presenting a

spike protein

fragment

ACTIVATED

KILLER

T CELL

Beginning to kill

the infected cell

INFECTED

CELL

ANTIGEN-

PRESENTING

CELL

Presenting a

spike protein

fragment

ACTIVATED

KILLER

T CELL

Beginning to kill

the infected cell

INFECTED

CELL

ANTIGEN-

PRESENTING

CELL

Presenting a

spike protein

fragment

ACTIVATED

KILLER

T CELL

Beginning to kill

the infected cell

INFECTED

CELL

ANTIGEN-

PRESENTING

CELL

Presenting a

spike protein

fragment

ACTIVATED

KILLER

T CELL

Beginning to kill

the infected cell

INFECTED

CELL

ANTIGEN-

PRESENTING

CELL

Presenting a

spike protein

fragment

ACTIVATED

KILLER

T CELL

Beginning to kill

the infected cell

INFECTED

CELL

Remembering the Virus

The Pfizer-BioNTech vaccine requires two injections, given 21 days apart, to prime the immune system well enough to fight off the coronavirus. But because the vaccine is so new, researchers don’t know how long its protection might last.

First dose

0.3ml

Second dose

21 days later

First dose

Second dose

21 days later

First dose

Second dose

21 days later

A preliminary study found that the vaccine seems to offer strong protection about 10 days after the first dose, compared with people taking a placebo:

Cumulative incidence of Covid-19

among clinical trial participants

2.5%

2.0

People taking

a placebo

1.5

1.0

Second

dose

First

dose

People taking the

Pfizer-BioNTech vaccine

0.5

0

1

2

3

4

8

12

16

Weeks after the first dose

Cumulative incidence of Covid-19

among clinical trial participants

2.5%

2.0

People taking

a placebo

1.5

1.0

Second

dose

People taking the

Pfizer-BioNTech

vaccine

First

dose

0.5

0

1

2

3

4

8

12

16

Weeks after the first dose

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 Pfizer’s Covid Vaccine: 11 Things You Need to Know.

Preparation and Injection

Each vial of the vaccine contains 5 doses of 0.3 milliliters. The vaccine must be thawed before injection and diluted with saline. After dilution the vial must be used within six hours.

A diluted vial of the vaccine at Royal Free Hospital in London.Jack Hill/Agence France-Presse

Vaccine Timeline

January, 2020 BioNTech begins work on a vaccine after Dr. Ugur Sahin, one of the company’s founders, becomes convinced that the coronavirus will spread from China into a pandemic.

Dr. Ugur Sahin of BioNTech.BioNTech

March BioNTech and Pfizer agree to collaborate.

May The companies launch a Phase 1/2 trial on two versions of a mRNA vaccine. One version, known as BNT162b2, had fewer side effects.

The first trial participant being vaccinated in Germany.BioNTech

July 22 The Trump administration awards a $1.9 billion contract for 100 million doses to be delivered by December, with an option to acquire 500 million more doses, if the vaccine is authorized by the Food and Drug Administration.

July 27 The companies launch a Phase 2/3 trial with 30,000 volunteers in the United States and other countries, including Argentina, Brazil and Germany.

Sept. 12 Pfizer and BioNTech announce they will seek to expand their U.S. trial to 44,000 participants.

A vial of the Pfizer-BioNTech vaccine.Pool photo by Andy Stenning

Nov. 9 Preliminary data indicates the Pfizer vaccine is over 90 percent effective, with no serious side effects. The final data from the trial shows the efficacy rate is 95 percent.

Nov. 20 Pfizer requests an emergency use authorization from the F.D.A.

Dec. 2 Britain gives emergency authorization to Pfizer and BioNTech’s vaccine, becoming the first Western country to give such an approval to a coronavirus vaccine.

Dec. 8 William Shakespeare, age 81, is among the first people to receive a shot of the vaccine in Britain, on the first day of vaccinations for at-risk health care workers and people over 80.

Dec. 9 Canada authorizes the Pfizer-BioNTech vaccine.

Dec. 10 Saudi Arabia approves the vaccine.

Dec. 11 The F.D.A. grants Pfizer-BioNTech vaccine the first emergency use authorization for a coronavirus vaccine in the United States. Mexico also approves the vaccine for emergency use.

Dec. 14 Vaccination begins in the United States.

Dec. 21The European Union authorizes the vaccine.

Dec. 31 Pfizer expects to produce up to 50 million doses by the end of the year, and up to 1.3 billion doses in 2021. Each vaccinated person will require two doses.

January, 2021 Scientists grow concerned about the emergence of fast-spreading variants that might be able to evade antibodies. Tests on a variant called P.1, first identified in Brazil, show that Comirnaty will likely work against it as well. However, researchers find that antibodies produced by Comirnaty are somewhat less effective against another variant called B.1.351, first identified in South Africa.

Feb. 15 Pfizer and BioNTech register a trial specifically for pregnant women.

Feb. 26 The companies announce a study to develop a B.1.351-specific booster.


Sources: National Center for Biotechnology Information; Nature; Florian Krammer, Icahn School of Medicine at Mount Sinai.

Tracking the Coronavirus

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