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 Moderna’s Vaccine Works
ByJonathan CorumandCarl ZimmerUpdatedMay 7, 2021
Moderna, a Massachusetts-based vaccine developer, partnered with the National Institutes of Health to develop and test acoronavirus vaccineknown asmRNA-1273. A clinical trial demonstrated that the vaccine has anefficacy rateofmore than 90 percentin preventing Covid-19.
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 thePfizer-BioNTech vaccine, Moderna’s 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 the vaccine, Moderna wraps 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. Moderna’s vaccine will need to be refrigerated, and should be stable forup to six monthswhen shipped and stored at –4°F (–20°C).
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
Moderna’s vaccine requires two injections, given 28 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
0.5ml
Second dose
28 days later
First dose
Second dose
28 days later
First dose
Second dose
28 days later
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.
An early study found that Moderna’s vaccine provides protectionfor at least three months.
For more about the vaccine, seeModerna’s Covid Vaccine: What You Need to Know.
Preparation and Injection
Each vial of the vaccine contains 10 doses of 0.5 milliliters. The vials need to be warmed to room temperature before injection. No dilution with saline is required.

Vaccine Timeline
January, 2020Moderna begins work on acoronavirus vaccine.
March 16Moderna scientists are the first to put aCovid-19 vaccine into human trials.
April 16Moderna announces that the United States government will provide $483 million in support for the design and testing of Moderna’s vaccine. Researchers at the National Institutes of Health will oversee much of the research, including the clinical trials.
July 27After initial studies yieldpromising results, Moderna and the N.I.H. begin Phase 3 testing on 30,000 volunteers across the United States. A quarter of the participants are 65 years or older.
July 28Moderna finds that the vaccineprotects monkeysfrom the coronavirus.
Aug. 11The United States governmentawardsthe company an additional $1.5 billion in exchange for 100 million doses, if the vaccine is authorized by the Food and Drug Administration.
Nov. 16Modernaannouncespreliminary data from its Phase 3 trial. Researchers estimate that the vaccine has anefficacy rateof 94.1 percent, far higher than experts had expected when vaccine testing began.
Nov. 30Modernaapplies for emergency use authorizationfrom the F.D.A.
Dec. 2Moderna registersa trialto test the vaccine on children between 12 and 18 years of age.
Dec. 18The F.D.A.authorizes the Moderna vaccinefor emergency use. The first injections of its vaccine could start on Dec. 21.
Dec. 23Canadaauthorizesthe vaccine.
Dec. 31The company expects to produce 20 million doses by the end of this year, and up to a billion doses in 2021. Each vaccinated person will require two doses.
Jan. 4, 2021Israelauthorizesthe vaccine for emergency use.
Feb. 25Modernaannouncesthey are working to produce between 600 million and a billion doses in 2021, and making investments to expand capacity up to 1.4 billion doses in 2022.
MarchModerna begins aPhase 1 trialof a vaccine made specifically for theB.1.351 variantand aPhase 1 trialof a new, refrigerator-stable vaccine.
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 29Modernaannouncesthey will produce 800 million to 1 billion doses in 2021, and plan to manufacture 3 billion doses in 2022.
Sources: National Center for Biotechnology Information; Nature; Florian Krammer, Icahn School of Medicine at Mount Sinai.
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