Two shots can prime the immune system to fight the coronavirus.
Two shots can prime the immune system to fight the coronavirus.
Covid-19Guidance
How the Pfizer-BioNTech Vaccine Works
ByJonathan CorumandCarl ZimmerUpdatedMay 7, 2021
The German companyBioNTechpartnered with Pfizer to develop and test acoronavirus vaccineknown asBNT162b2, the generic nametozinameranor the brand nameComirnaty. A clinical trial demonstrated that the vaccine has anefficacy rateofover 90 percentin preventing Covid-19.
Producing abatch of the Pfizer-BioNTech vaccinecurrently takes 60 days.
A Piece of the Coronavirus
The SARS-CoV-2 virus isstudded with proteinsthat it uses to enter human cells. These so-called spike proteins make a tempting target for potentialvaccinesandtreatments.
Spikes
Spike
protein
gene
Spikes
Spike
protein
gene
CORONAVIRUS
Like theModerna vaccine, the Pfizer-BioNTech vaccine is based on the virus’sgenetic instructionsfor 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 anycoronavirus-infected cellsthat 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 protectionabout 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, seePfizer’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.

Vaccine Timeline
January, 2020BioNTechbegins workon a vaccine after Dr. Ugur Sahin, one of the company’s founders, becomes convinced that the coronavirus will spread from China into a pandemic.
MarchBioNTech and Pfizer agree to collaborate.
MayThe companies launch aPhase 1/2 trialon two versions of a mRNA vaccine. One version, known as BNT162b2, had fewer side effects.
July 22The Trump administrationawardsa $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 27The companieslauncha Phase 2/3 trial with 30,000 volunteers in the United States and other countries, including Argentina, Brazil and Germany.
Sept. 12Pfizer and BioNTechannouncethey will seek to expand their U.S. trial to 44,000 participants.
Nov. 9Preliminary data indicates the Pfizer vaccine isover 90 percent effective, with no serious side effects. The final data from the trial shows the efficacy rate is 95 percent.
Nov. 20Pfizer requests anemergency use authorizationfrom the F.D.A.
Dec. 2Britain givesemergency authorizationto Pfizer and BioNTech’s vaccine, becoming the first Western country to give such an approval to a coronavirus vaccine.
Dec. 8William 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. 9Canadaauthorizesthe Pfizer-BioNTech vaccine.
Dec. 10Saudi Arabiaapprovesthe vaccine.
Dec. 11The F.D.A. grants Pfizer-BioNTech vaccine the firstemergency use authorizationfor a coronavirus vaccine in the United States.Mexicoalso approves the vaccine for emergency use.
Dec. 14Vaccination beginsin the United States.
Dec. 21The European Unionauthorizesthe vaccine.
Dec. 31Pfizer expects to produce up to50 million dosesby the end of the year, and up to 1.3 billion doses in 2021. Each vaccinated person will require two doses.
January, 2021Scientists grow concerned aboutthe emergence of fast-spreading variantsthat might be able to evade antibodies. Tests ona variant called P.1, first identified in Brazil, show that Comirnatywill likely work against it as well. However, researchers find that antibodies produced by Comirnaty aresomewhat less effectiveagainst another variant calledB.1.351, first identified in South Africa.
Feb. 15Pfizer and BioNTechregister a trialspecifically for pregnant women.
Feb. 26The companiesannouncea study to develop a B.1.351-specific booster.
April 16Pfizer says their vaccine may require athird dosewithin a year of the initial inoculation, followed by annual vaccinations.
April 20Some vaccinated people areprofessing loyaltyto the brand they happened to have received.
April 25Nearly 8 percent of Americans who got initial Pfizer or Moderna shots havemissed their second doses.
April 28Pfizer has delivered more than150 million doses of the vaccineto the United States, and expects to double that number by mid-July.
May 7Pfizer and BioNTechapply for full approvalfrom the U.S. Food and Drug Administration.
Sources: National Center for Biotechnology Information; Nature; Florian Krammer, Icahn School of Medicine at Mount Sinai.
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