[Originally published: October 18, 2021. Updated: November 24, 2021.]
In October, the Food and Drug Administration (FDA) authorized a Johnson & Johnson COVID-19 booster shot. The booster allows anyone who got the company’s initial one-shot to get an added dose of protection at least two months later. In addition, a new “mixand-match” strategy provided the option of choosing another company’s vaccine as a booster.
The Centers for Disease Control and Prevention (CDC)’s approval of the FDA authorizations came after J&J announced in a press release in early October that new data—including 94% efficacy against symptomatic disease after a booster—put its vaccine on par with the mRNA COVID-19 vaccines from Pfizer-BioNTech and Moderna.
Late last year—after all three vaccines were authorized for use in the United States—some people expressed concern about the efficacy of J&J’s single-shot vaccine, which trailed behind the Pfizer and Moderna vaccines, based on data from their clinical trials at that time. (Pfizer’s and Moderna’s two-dose primary series were each around 94% protective against symptomatic disease; J&J’s was 66% and about 72% in the U.S. alone.) The J&J vaccine also hit roadblocks when rare complications made big news last spring, and the Centers for Disease Control and Prevention (CDC) and FDA recommended a brief pause in its use. These issues may have contributed to reduced public confidence in the vaccine.
Far more people in the U.S. are vaccinated with the Pfizer or Moderna vaccines. As of mid-October 2021, more than 15 million Americans were fully vaccinated with the J&J vaccine, compared to more than 69.6 million who received Moderna and 104.6 million who received Pfizer, according to the CDC.
We sat down with Yale Medicine infectious disease and community health doctors, who answered commonly asked questions about the J&J booster.
1. What does the new J&J data show?
J&J data on its vaccine’s efficacy—post-booster shot—is from a large global study, the details of which are available on the FDA’s website (as part of the Vaccines and Related Biological Products Advisory Committee [VRBPAC] briefing document used in the mid-October FDA panel meeting to discuss authorization of the booster). The company reports that, in addition to providing 94% protection against moderate-to-severe COVID-19 in the U.S. (that figure was 75% in all of the countries studied), a booster shot given two months after the initial dose increased antibody levels by four to six times, compared to one dose alone.
Leslie Sude, MD, a Yale Medicine pediatrician with an interest in community medicine, says the data, once it’s finalized, could put Johnson & Johnson’s vaccine in a new light.
A real-world study from the CDC, conducted from March through August, showed the J&J single shot to be only 71% effective against hospitalization from COVID-19 in U.S. adults without immunocompromising conditions, compared to 93% for Moderna and 88% for Pfizer. “But with the booster dose, the J&J vaccine could be equivalent to the mRNA vaccines,” Dr. Sude says. “Some vaccine experts feel that the J&J vaccine should have always been a two-dose series, but have only recently reached the phase of vaccine efficacy monitoring to confirm that idea.”
2. What does '71% effective against hospitalization' in the CDC study really mean?
Most studies of vaccine efficacy against hospitalization follow people who are vaccinated and those who are unvaccinated forward through time (in what’s called a “prospective” study) to determine risk of hospitalization.
The CDC study, however, is a retrospective case-control study, which uses information that occurred in the past. That means the study authors reviewed records of all adults (without immunocompromising conditions) who were admitted to the hospital with flu-like symptoms at a certain point in time. They then compared “cases” (i.e., those diagnosed with COVID-19) to “controls” (i.e., those who did not have COVID-19 and were instead diagnosed with something else) in terms of vaccination status and vaccination type. Overall, 12.9% of participants were fully vaccinated with Moderna, 20.0% with Pfizer, and 3.1% with J&J.
So, in the CDC study, the authors are saying that among people with symptoms of a respiratory infection who were admitted to the hospital, those diagnosed with something else were 71% more likely to have been vaccinated with J&J (93% with Moderna, 88% with Pfizer, respectively) compared to those who were diagnosed with COVID-19. Importantly, too, cases and controls were not matched on other characteristics that may affect vaccination status or health outcomes (such as age, race/ethnicity, sex, socioeconomic status, insurance status, medical comorbidities, etc.).
"All of this means that all three vaccines are highly effective at preventing hospitalization from COVID-19. If you are fully vaccinated and develop flu-like symptoms requiring hospitalization, you are likely to be infected with something else besides COVID-19. But that likelihood is even greater if you received Moderna or Pfizer vaccines," says Jaimie Meyer, MD, MS, a Yale Medicine infectious diseases physician. "This may be because the Moderna and Pfizer vaccines use a different type of technology and involved a 2-dose primary series, or because so many more people received Moderna and Pfizer vaccines that we have much more supportive data."
3. Why did the FDA question the strength of J&J’s data?
Even though the FDA advisory panel unanimously recommended authorization, the FDA had questioned a test Johnson & Johnson used in the trial to support its application for authorization. Regulators questioned the accuracy of a test called pseudovirus neutralization assay (psVNA), which is used to measure antibodies, suggesting that the low-test sensitivity could have affected the results of the clinical trial.
“The upshot, though, is that despite the concern for low sensitivity of the psVNA, the advisory panel still recommended the second dose,” says Dr. Sude. “They feel that everyone who received a first dose should be given the option to optimize protection based on the best data available at this time.”
4. Will the J&J booster be available to everyone?
The FDA advisory panel is recommending Johnson & Johnson’s booster be given to all adults ages 18 and older who got the single shot as soon as two months after the initial dose. CDC interim guidelines recommend moderately and severely immunocompromised people who received one dose of the J&J vaccine get a second dose of either an mRNA or J&J vaccine at least two months after their initial shot.
This broad recommendation for the J&J booster is in contrast to the specific recipient recommendations for the Pfizer booster, which was authorized in September. The CDC recommended the Pfizer booster only for people ages 65 and up, residents of long-term care settings, and people ages 18 to 64 with underlying medical conditions or whose work may put them at higher risk of exposure to COVID-19. The recommendation was for the booster shot to be given 6 months after the second Pfizer dose.
In October, the FDA made a similar booster recommendation—in terms of who should receive it—for Moderna. The Moderna booster is a reduced dose to be given at least 6 months after the second Moderna shot.
Dr. Meyer says it’s important to remember that authorizing boosters for everyone might not be the best strategy. “Boosters don't work equally as well across an entire population,” she says. “There are certain groups of people who stand to benefit more from boosters than others, in terms of the overall public health approach to the pandemic, either because they're at very high risk of severe disease—or because of exposure.”
5. If you had the J&J shot, can you get a booster of Pfizer or Moderna instead?
The CDC’s approval of the mix-and-match authorization follows a report of early data from a federal clinical trial suggested it might be better for J&J recipients to get an mRNA vaccine booster (from Pfizer or Moderna). The trial’s preliminary data showed that people who had gotten the J&J vaccine followed by a Moderna booster had a 76-fold rise in antibodies in 15 days; those who got Pfizer saw a 35-fold increase; while those who got the J&J booster had only a four-fold increase. That data was published in a preprint and has not yet undergone independent peer review.
6. Wouldn’t a J&J booster take away from its one-shot convenience?
Some people might still get J&J’s single shot, but not follow up with a booster if it becomes available. Although it’s ideal for people to get the booster, for those who don’t, getting one shot is still important, says Dr. Meyer, adding that it's better to have a baseline level of protection from a one-shot vaccination than it is to be completely unvaccinated. “It’s better to think of boosters as a way to get the most impact.”
Dr. Sude reminds people that in the world of vaccines, experts considered Johnson & Johnson’s shot to be a strong vaccine from the beginning. The cutoff for FDA authorization of any COVID-19 vaccine has been 50% efficacy, she says, and all of the vaccines authorized in the U.S. surpassed that. “While Johnson & Johnson has always been a very good vaccine for many people, a booster—or what we may eventually call a ‘standard second dose’—would make it a better one,” she says.
7. What should you know about the FDA warning labels attached to J&J’s vaccine?
All three vaccines available in the United States have had their setbacks, including reports of adverse events, but these have been rare. The FDA added warnings to the Pfizer and Moderna vaccines following reports of rare cases of myocarditis and pericarditis after mRNA vaccination, particularly in male adolescents and young adults.
For people who got Johnson & Johnson, the FDA has added two warnings to the vaccine. The first was this past April, after the vaccination was linked to a small number of cases of an uncommon, but potentially serious blood clotting disorder, prompting the agency to put a two-week pause on the vaccine while the issue was investigated. The second was in July, after reports linked the vaccine to Guillain-Barré syndrome, a rare neurological disorder. In both cases, the agency said the incidence was very rare, and the benefits of the vaccine still outweighed the risks.
8. Should you still choose the J&J vaccine?
Both doctors say that, from their perspective as clinicians—and from a “population health” standpoint—it’s most important to vaccinate as many people as possible against COVID-19, regardless of which vaccine is used. They say this will provide better protection for everyone—in the U.S. and around the world—because it will leave the virus with fewer people to infect and cases will go down.
“There are risks and benefits with anything we do,” Dr. Meyer says. “There are some people who are going to have trouble getting the mRNA two-dose primary series. For that group, J&J is absolutely the right choice. It’s good to be able to give people different options that work for their lives.”
Dr. Sude recalls time she spent earlier this year on a mobile health van, inoculating people in the community. Many chose the J&J single shot when they thought it might be difficult to come back for a second shot because they didn’t have a primary care doctor, regular contact with the health care system, or access to technology to help them schedule vaccinations.
Part of those decisions may simply have come down to the ability to choose. “We've noticed an uptick in vaccinations when we started offering brief explanations of each vaccine and then asking people which one they would prefer to receive,” says Dr. Sude. “Giving people the power to choose seems to bring them to vaccination with more confidence and security rather than being told, ‘This is your only option.’”
Giving J&J vaccine recipients the option of a booster can only help, she adds.