Comparing three Covid-19 vaccines: Pfizer, Moderna, J&J – STAT

In an ideal world, a pandemic vaccine could be delivered in a single shot, so supplies could be stretched to cover a lot of people. It would trigger no side effect more significant than a sore arm. And it would be easy to ship and store.

Soon, it seems, this ideal of a Covid-19 vaccine will be within reach. 

Last Friday, Johnson & Johnson announced that a one-dose vaccine being developed by its vaccines division, Janssen Pharmaceuticals, had been shown to be 66% protective against moderate to severe Covid infection in a multicountry study. But, importantly, it was 85% effective in protecting against severe disease. And there were no hospitalizations or deaths among people in the vaccine arm of a large clinical trial. 

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Overall efficacy varied a bit geographically, especially in South Africa, where a new variant appears to evade to some degree the immunity induced both by infection and by Covid vaccines, which were designed to target earlier strains of the SARS-CoV-2 virus.

Johnson & Johnson said it will apply to the Food and Drug Administration for an emergency use authorization this week. That means sometime later this month or early in March its vaccine will likely start to be used in the United States, though the company is not expected to be able to supply substantial numbers of doses until April.

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Earlier STAT published a head-to-head comparison of the vaccines developed by Pfizer and its partner, BioNTech, and by Moderna, which have been in use in the country since December. We’re updating it here with information about the J&J vaccine, with the caveat that some data from this likely new entry to the U.S. vaccination program haven’t yet been made public.

Please note that in the initial rollout of vaccine, individuals are unlikely to 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. 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 SARS-2 spike protein and to introduce the spike to the immune system, prompting it to recognize SARS-2 and protect against it. J&J used this same approach to make an Ebola vaccine that has been authorized for use by the European Medicines Agency.

Target population

The Pfizer vaccine has been authorized for use for people aged 16 and older. 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, so for the time being, this vaccine won’t be available for use in children and teens under 18 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. 

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 efficacy in 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 were testing for slightly different criteria, with Pfizer counting cases from seven days after receipt of the second dose of vaccine and Moderna waiting till day 14 to start counting cases. Both tested for any symptomatic Covid infection.

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.

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 countries (eight) or regions (three) 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.

Side-effect profile

In the vernacular of vaccinology, vaccines 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, has advised hospitals they may want to stagger vaccinations among employees  — for instance, don’t vaccinate all emergency room staff at the same time — 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. 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.

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. 

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 2.1 cases per one million doses given of the Moderna vaccine, and 6.2 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. 

To date the J&J vaccine has not been associated with anaphylactic reactions.

Safety for those who are pregnant or lactating

None of the vaccines has been tested in these two groups.

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.

Pfizer has only interim data from its animal studies, but said it saw no concerning signs either.

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.

The J&J vaccine hasn’t yet been through the regulatory process, so it’s too early to say what the FDA and the CDC will recommend. The company plans to include pregnant women in clinical trials in the near future, a spokesman told STAT.

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 does not, which means this vaccine can be given easily anywhere, once supplies are adequate. Doctors’ offices, pharmacies, mass vaccination sites, public health clinics — this vaccine will be much easier to use. It can be stored for at least three months at the temperature of a regular refrigerator.

Of the mRNA vaccines, Moderna’s is far easier to use than Pfizer’s. For starters, Moderna’s must be shipped at -4 Fahrenheit; Pfizer’s must be shipped and stored at -94 Fahrenheit. The former is the temperature of a regular refrigerator freezer; the latter requires special ultracold freezers. Doctors’ offices do not have ultracold freezers; neighborhood pharmacies don’t either.

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. STAT asked J&J how long its vaccine will last once a vial has begun to be used, but so far the company has not provided that information.

Minimum purchase order

The ultracold storage requirement is not the only challenging aspect of the Pfizer vaccine. The minimum amount of vaccine a location can order is 975 doses. A large teaching hospital might need several of those. But there are plenty of places across the country that don’t need 975 doses to vaccinate the people currently eligible for vaccination — health workers and nursing home residents. This is the vaccine that needs to be kept at -94 F. The minimum order size will limit the locations in which this vaccine can be used.

The Moderna vaccine’s minimum order is 100 doses, a much more manageable number.

STAT asked J&J what its minimum order will be; it declined to say.

The Pfizer vaccine is shipped in six-dose vials. Moderna’s vaccine comes in 10-dose vials. J&J’s vaccine will be 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.