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.
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.
If you value our coronavirus coverage, please consider making a one-time contribution to support our journalism.
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.
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.
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.
The story of mRNA: How a once-dismissed idea became a leading technology in the Covid vaccine race
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.
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.
Sign up for Daily Recap
A roundup of STAT’s top stories of the day.
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.
‘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.
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.
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.
What do you think about this article? Let us know your comment.