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COMPARING THE COVID-19 VACCINES DEVELOPED BY PFIZER, MODERNA, AND JOHNSON &
JOHNSON

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By Helen Branswell Feb. 2, 2021

Reprints
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CVS registered pharmacist Ken Ramey prepares to give a Covid-19 vaccine at the
Isles of Vero Beach assisted and independent senior living community in Vero
Beach, Fla. Wilfredo Lee/AP
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Scientific teams around the world have developed successful Covid-19 vaccines in
incredibly short order. In a feat that even a couple of years ago would have
seemed completely out of reach, vaccines to protect against the new disease were
being used before the first anniversary of the disclosure that a new threat
existed. This is truly extraordinary.

In the United States so far, three vaccines have been issued emergency use
authorizations — green lights from the Food and Drug Administration to be put
into use, even though they have not yet been fully licensed.

A vaccine developed by the partnership of Pfizer and German-manufacturer
BioNTech came first in mid-December, followed closely by one developed by
Moderna with assistance from the National Institute of Allergy and Infectious
Diseases.

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In late February came a third. Janssen Pharmaceuticals, the vaccine division of
Johnson & Johnson, secured an emergency use authorization for its one-dose
vaccine. The vaccine was seen as a potential game-changer. It doesn’t require
the fussy cold-chain needed to keep the Pfizer and Moderna vaccines from
spoiling. It is cheaper, both on a per-dose basis and because only one dose is
needed. Plus it was thought a one-and-done option might entice some people who
couldn’t easily get two doses to roll up their sleeves.

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But since the J&J vaccine’s arrival on the scene there have been a number of
challenges. A production snafu in the hands of a contract production company
contaminated 15 million doses, which had to be destroyed. And in mid-April, the
FDA and CDC recommended states pause use of the vaccine as they investigate
whether the vaccine triggers a rare but serious side effect — the development of
diffuse blood clots, even though the few individuals who developed the condition
had low platelet levels.

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What follows is a head-to-head comparison of the vaccines developed by Pfizer
and BioNTech, by Moderna, and by J&J. This article will be updated as
developments occur.

Please note that in the initial rollout of vaccine, individuals may not be
offered a choice of which vaccine they want. Supplies are too scarce. The
vaccine available at the place where you are being vaccinated is the one you’ll
get.


VACCINE TYPES

The Pfizer and Moderna vaccines are made using messenger RNA, or mRNA, a
technology that delivers a bit of genetic code to cells — in effect, a recipe to
make the surface protein (known as spike) on the SARS-2 virus. The proteins made
with the mRNA instructions activate the immune system, teaching it to see the
spike protein as foreign and develop antibodies and other immunity weapons with
which to fight it.

The J&J vaccine uses a different approach to instruct human cells to make the
SARS-2 spike protein, which then triggers an immune response. It is what’s known
as a viral vectored vaccine. A harmless adenovirus — from a large family of
viruses, some of which cause common colds — has been engineered to carry the
genetic code for the SARS-2 spike protein. Once the adenovirus enters cells,
they use that code to make spike proteins.  J&J employed this same approach to
make an Ebola vaccine that has been authorized for use by the European Medicines
Agency.

Related:


THE STORY OF MRNA: HOW A ONCE-DISMISSED IDEA BECAME A LEADING TECHNOLOGY IN THE
COVID VACCINE RACE


TARGET POPULATION

The Pfizer vaccine has been authorized for use for people aged 16 and older,
though the company has recently asked the FDA to change the label to allow
children 12 and older to be vaccinated. Moderna’s has been cleared for use in
people 18 and older, though the company is now testing its vaccine in 12- to
17-year-olds. J&J’s vaccine has been tested in people 18 and older, and that’s
who it was authorized for. Until testing in children and younger teens is
conducted, this vaccine won’t be available for use anyone under 18 years old
either.


VACCINE EFFICACY

The Pfizer and Moderna vaccines have shown astonishing — and essentially
equivalent — degrees of efficacy, at least in the early stages after
vaccination.

The Pfizer vaccine showed efficacy of 95% at preventing symptomatic Covid
infection after two doses. The vaccine appeared to be more or less equally
protective across age groups and racial and ethnic groups.

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The Moderna vaccine was 94.1% effective at preventing symptomatic Covid-19 after
the second dose. The vaccine’s efficacy appeared to be slightly lower in people
65 and older, but during a presentation to the Food and Drug Administration’s
advisory committee in December, the company explained that the numbers could
have been influenced by the fact there were few cases in that age group in the
trial. The vaccine appeared to be equally effective across different ethnic and
racial groups.

But comparing the efficacy of those vaccines to the efficacy of Johnson &
Johnson’s is challenging because of differences in the designs of the Phase 3
clinical tests — essentially the trials were testing for different outcomes.
Pfizer’s and Moderna’s trials both tested for any symptomatic Covid infection.
Pfizer started counting cases from seven days after receipt of the second dose
of vaccine, while Moderna waited until day 14 to start counting cases.

J&J, by contrast, sought to determine whether one dose of its vaccine protected
against moderate to severe Covid illness — defined as a combination of a
positive test and at least one symptom such as shortness of breath, beginning
from 14 or 28 days after the single shot. (The company collected data for both.)

Because of the difference in the trials, making direct comparisons is a bit like
comparing apples and oranges. Additionally, Pfizer and Moderna’s vaccines were
tested before the emergence of troubling new variants in Britain, South Africa,
and Brazil. It’s not entirely clear how well they will work against these
mutated viruses.

The J&J vaccine was still being tested when the variants were making the rounds.
Much of the data generated in the South African arm of the J&J trial involved
people who were infected with the variant first seen in South Africa, called
B.1.351.

Related:


‘A FULL COURT PRESS’: BANKING ON TECH BACKUP, CDC LAUNCHES NATIONWIDE
VACCINEFINDER TOOL

The J&J one-dose vaccine was shown to be 66% protective against moderate to
severe Covid infections overall from 28 days after injection, though there was
variability based on geographic locations. The vaccine was 72% protective in the
United States, 66% protective in South America, and 57% protective in South
Africa.

But the vaccine was shown to be 85% protective against severe disease, with no
differences across the eight countries or three regions in the study, nor across
age groups among trial participants. And there were no hospitalizations or
deaths in the vaccine arm of the trial after the 28-day period in which immunity
developed.

It’s not yet known if any of these vaccines prevent asymptomatic infection with
the SARS-CoV-2 virus. Nor is it known if vaccinated people can transmit the
virus if they do become infected but don’t show symptoms.


NUMBER OF DOSES/AMOUNTS OF VACCINE PER DOSE

Both the Moderna and the Pfizer vaccines require two shots: a priming dose,
followed by a booster shot. The interval between Moderna doses is 28 days; for
the Pfizer vaccine, it’s 21 days.

Each dose of Pfizer’s contains 30 micrograms of vaccine. Moderna went with a
much larger dose of vaccine, 100 micrograms. It means the company is using a
little more than three times as much vaccine per person as Pfizer is. And yet,
they aren’t getting better results. The government’s vaccine development
program, formerly called Operation Warp Speed, has asked Moderna to test if it
could lower the dosage of its vaccine without eroding the vaccine’s protection.

The J&J vaccine is, as mentioned, a single-dose vaccine. The company is also
testing a two-dose regimen, with the two shots given eight weeks apart. The
results from that 30,000-person trial aren’t expected until sometime in May.

J&J is also testing what happens to antibody responses when a person who
received the single dose regimen receives a small booster shot quite a bit
later, Johan Van Hoof, managing director of Janssen Vaccines revealed recently.
Van Hoof didn’t say how long the interval is between the single shot and the
small booster, nor did he say when J&J expects results from that study.


SIDE-EFFECT PROFILE

In the vernacular of vaccinology, shots that trigger a range of transient side
effects in a lot of recipients are known as reactogenic.

All of these vaccines — in fact, most if not all the Covid-19 vaccines that have
reported data so far — fall into the reactogenic category. The Advisory
Committee on Immunization Practices, an expert panel that helps the Centers for
Disease Control and Prevention set vaccination policies, advised hospitals early
in the rollout that they might want to stagger vaccinations among employees in
case some feel too unwell to work the day after being vaccinated.

The most common side effects are injection site pain, fatigue, headache, muscle
pain, and joint pain. Some people in the clinical trials have reported fever.
With the Pfizer and Moderna vaccines, side effects are more common after the
second dose. Younger adults, who have more robust immune systems, reported more
side effects than older adults.

To be clear: These side effects are a sign of an immune system kicking into
gear. They do not signal that the vaccine is unsafe. To date there are no
serious, long-term side effects associated with receipt of these vaccines, which
will be closely monitored as their use expands.

Related:


AMAZON ESTABLISHED A FOOTHOLD IN DIAGNOSTICS DURING COVID-19. NOW IT’S DOUBLING
DOWN

There have been reports of severe allergic reactions to the mRNA vaccines. Both
the Pfizer and Moderna vaccines appear, on rare occasions, to trigger
anaphylaxis, a severe and potentially life-threatening reaction. People who
develop anaphylaxis must be treated with epinephrine — the drug in EpiPens — and
may need to be hospitalized to ensure their airways remain open. The CDC says
people should be monitored for 15 minutes after getting a Covid-19 shot, and 30
minutes if they have a history of severe allergies. J&J recently revealed that a
single case of anaphylaxis has been reported in someone who received its
vaccine.

It will take time to come up with a firm estimate of how frequently this side
effect occurs. The most recent data from the CDC suggest that anaphylaxis occurs
at a rate of about 2.5 cases per one million doses given of the Moderna vaccine,
and 4.7 cases per million doses of the Pfizer. Many of the people who have
developed anaphylaxis have a history of severe allergies and some have had
previous episodes of anaphylaxis.

The J&J also appears to have a serious — thought different — problem. A small
number of individuals who received the vaccine have gone on to develop
thrombotic events in the week or two after vaccination; one has died. The
thrombotic events include diffuse clots and low platelet levels, an unusual
combination that can be dangerous if treated improperly. The normal treatment
for clots — a blood thinner called heparin — would make the problem worse, the
FDA said, warning doctors to ask for a Covid-19 vaccination history if they see
patients with that configuration of symptoms.

This problem has led the FDA and the Centers for Disease Control and Prevention
to urge states to suspend use of the J&J vaccine while they investigate these
events.


SAFETY FOR THOSE WHO ARE PREGNANT OR LACTATING

None of the vaccines has been tested in these two groups, although Pfizer
recently began a Phase 2/3 trial to test the safety and efficacy of its vaccine
during pregnancy. Van Hoof said J&J will begin a similar trial in late March or
early April.

Moderna has completed animal studies the FDA demanded of manufacturers; these
studies look for evidence that the vaccine might harm the pregnancy or the
developing fetus. The company said it saw no such signals.

The CDC recommends until those studies are conducted, the choice of whether to
get vaccinated should rest with the person who is pregnant or lactating. This is
a more permissive stance than has been taken in some countries, which have said
people who are pregnant should not be vaccinated with these vaccines.


STORAGE REQUIREMENTS

The mRNA vaccines require an elaborate cold chain, the term used to describe the
conditions under which vaccines must be stored during distribution and when they
are in the doctors’ offices, pharmacies, or public health clinics where they’ll
be administered.

The J&J shot does not, which means this vaccine can be given easily anywhere —
in  doctors’ offices, pharmacies, mass vaccination sites, public health clinics
— once supplies are adequate. It can be stored for at least three months at the
temperature of a regular refrigerator.

Of the mRNA vaccines, Pfizer’s was originally the more difficult to use. It had
to be shipped and stored in ultra-cold freezers — ones that could keep the vials
at -94 degrees Fahrenheit. But recently, the FDA announced that the vaccine can
be shipped and stored — for a two-week period only — at temperatures of normal
pharmacy freezers, between -13 and 5 degrees Fahrenheit. That should make the
final stage of the vaccine’s journey from production plant to syringe ready to
plunge into an arm somewhat easier.

Related:


‘AN UNCHARTERED SITUATION FOR ALL OF US’: FROM SHIPPING CONTAINERS TO SECURITY
CONCERNS, A COVID-19 VACCINE SUPPLY CHAIN TAKES SHAPE

Moderna’s must be shipped at -4 degrees Fahrenheit, which is within the
temperature of a regular refrigerator freezer.

After thawing, a vial of the Pfizer vaccine must be used within five days;
Moderna’s is stable at fridge temperature for 30 days and at room temperature
for 12 hours. J&J’s vaccine can be stored at room temperature — not to exceed 77
degrees Fahrenheit — for 12 hours when the vial hasn’t yet been punctured. After
the first dose is withdrawn, the vial can be stored in a fridge for six hours or
at room temperature for two hours.


MINIMUM PURCHASE ORDER

The cold-chain requirement is not the only challenging aspect of the Pfizer
vaccine. The minimum amount of vaccine a location can order is 1,170 doses. A
large teaching hospital might need several of those. But there are plenty of
places across the country that would not have needed 1,000 doses to vaccinate
the people eligible for vaccination in the early stages of the rollout, when
only selected groups of people were eligible to get vaccine. As states move into
vaccinating larger segments of the population, this large minimum order size
become less of a disadvantage.

The Moderna vaccine’s minimum order is 140 doses, a much more manageable number.

STAT has asked J&J several times what its minimum order will be; the company has
not yet disclosed that information.

The Pfizer vaccine is shipped in six-dose vials. Moderna’s vaccine comes in
14-dose vials. J&J’s vaccine is packaged in five-dose vials.


DURABILITY OF PROTECTION

Figuring out how long the protection provided by any of these vaccines will last
will take time. It’s going to involve periodic blood draws from some volunteers
to see what their antibody levels look like, though a decline in antibody levels
doesn’t necessarily equate to loss of protection.

But a large part of this work will involve watching for reports that people who
were immunized are starting to contract Covid in larger numbers, a development
that would probably lead to recommendations to give people booster shots at some
yet-to-be-determined interval.

This story was last updated on April 13. An earlier version of this story
mischaracterized the way in which viral vectored vaccines work and incorrectly
stated that the single dose J&J vaccine contains more antigen than the doses in
its two-dose regimen. 

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ABOUT THE AUTHOR REPRINTS


HELEN BRANSWELL

Senior Writer, Infectious Disease

Helen covers issues broadly related to infectious diseases, including outbreaks,
preparedness, research, and vaccine development.


@HelenBranswell


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 * Jeanne Ames says:
   February 2, 2021 at 7:52 pm
   
   Yes, I would like to know if any of these vaccines does or does not have
   sulfites in them. I’m very allergic to sulfites and I can’t even use an
   epi-pen because epipens have sulfites in them also. Please let me know if one
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   THANKS SO CLEAR GREAT JOB

   

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