In mix-and-match booster landscape, don’t rule out Johnson & Johnson, experts say

But vaccine experts agree it’s too early to say what impact that finding will have.

“The answer is it could, but it shouldn’t” make the J&J vaccine less attractive, said Dr. Peter Hotez, codirector of the Center for Vaccine Development of Texas Children’s Hospital, who had no role in the development of the three US vaccines. “It’s a very good vaccine, but probably always should have been put out as a two-dose vaccine to begin with.”

A separate scientific panel that advises the Centers for Disease Control and Prevention voted unanimously on Thursday to recommend boosters for people who received the Moderna and J&J vaccines, as it had in September for Pfizer recipients. The committee also said it was fine for people to select the booster they wanted, no matter which one they previously received.

Hotez is among several experts who say the first results of an ongoing National Institutes of Health study presented this month to the FDA advisory panel addressed only one of the immune responses stimulated by the three boosters, the quantity of antibodies, and even that was just an early snapshot.

The small study of about 450 vaccine recipients didn’t address other related matters, including the durability of the antibodies generated by the J&J shot, which appears greater than those generated by the messenger RNA vaccines of Pfizer and Cambridge-based Moderna.

The J&J vaccine, which uses a harmless cold virus to deliver part of the coronavirus to stimulate immunity, also can be refrigerated for prolonged periods rather than having to be kept frozen like the mRNA vaccines, a distinct advantage in rural America and in undeveloped countries. In addition, the mRNA vaccines have been linked to different rare side effects than those associated with the J&J vaccine, and different demographic groups are more at risk.

“The J&J vaccine still has very good protection against severe illness and death,” said Dr. Kirsten Lyke, a professor at the University of Maryland School of Medicine, who presented the results of the NIH study to the FDA committee that authorized J&J and Moderna boosters. Lyke, an investigator in studies of the Pfizer and Moderna vaccines, cautioned against making “two-dimensional” comparisons.

J&J’s vaccine accounted for less than 4 percent of coronavirus vaccine doses administered nationwide, or about 15 million shots as of Thursday, according to the US Centers for Disease Control and Prevention. That compares with more than 240 million doses of the Pfizer vaccine and over 154 million of Moderna’s.

The FDA cleared J&J’s vaccine for emergency use in late February, two months after the agency authorized the two-dose Pfizer and Moderna vaccines. From the onset, the shot has been marketed as an appealing “one and done” alternative.

But its rollout was hobbled by an 11-day pause in April, as regulators investigated an increased risk of rare but severe blood clots, chiefly in younger women. And millions of doses of the J&J vaccine produced by a problem-plagued Emergent BioSolutions plant in Baltimore were ordered thrown out in the spring because of possible contamination.

The J&J vaccine also has consistently shown a lower level of effectiveness than the Pfizer and Moderna vaccines, although comparisons are challenging because of differences in the designs and the timing of late-stage clinical trials.

In a large study, Pfizer’s vaccine showed efficacy of 95 percent at preventing symptomatic COVID-19, while Moderna’s was 94.1 percent effective.

In contrast, the J&J vaccine was shown to be 66 percent protective against moderate to severe COVID-19 infections, although that varied based on geographic locations. The vaccine was 72 percent protective in the United States, 66 percent protective in South America, and 57 percent protective in South Africa. One shot was shown to be 85 protective against severe cases of the disease, regardless of location.

As the highly contagious Delta variant surged in recent months and health officials reported breakthrough infections, the NIH launched a study to determine whether switching from one vaccine to another for booster doses provided more protection than sticking with the same vaccine. Scientists have long known that a mix-and-match approach can broaden immune responses against infectious diseases.

NIH researchers organized nine groups of roughly 50 people each. Each group received one of the three vaccines, followed by a booster. Volunteers in three groups received the same vaccine for a boost. Those in the other six were switched to a different shot.

Changing vaccines raised the level of antibodies, regardless of which combination people got, and there were no serious side effects. But the results for people who originally got the J&J shot revealed the stark disparities that the FDA panel was later told about.

Lyke, of the University of Maryland, emphasized that the NIH study is continuing and has yet to report how well different boosters increase T cells, a white blood cell considered an important weapon in the immune system. The J&J vaccine generates T cells better than Pfizer or Moderna, she said, and that could become clearer when the booster study yields more results, probably next month.

Although the World Health Organization declared COVID-19 a pandemic 19 months ago, scientists still haven’t established what biological benchmarks in the blood are necessary to indicate protection from the virus, and many questions remain unanswered.

For instance, if J&J recipients’ antibody levels rise by seventy-sixfold after they receive a Moderna booster compared with fourfold after a second J&J shot, does that mean the J&J booster is ineffective?

Not necessarily, said Lyke, adding, “I think fourfold isn’t bad.”

Dr. Dan Barouch, head of the Center for Virology and Vaccine Research at Beth Israel, which helped develop the J&J vaccine, said, “Fundamentally, we still don’t know the correlates of protection. Most people agree that neutralizing antibodies probably play some role, but also that they don’t play the entire role.”

As an example, he said one shot of the J&J vaccine produces higher levels of so-called killer T cells that clear an infection than two shots of either mRNA vaccine.

In addition, Barouch pointed to a study published Oct. 15 in the New England Journal of Medicine involving a few dozen subjects at Beth Israel. He was the lead author. The paper found that antibody levels in people who received two shots of the Pfizer or Moderna vaccines were much higher initially than those stimulated by the one-shot J&J vaccine, but those levels waned faster than J&J’s. All three vaccines had similar antibody levels after eight months.

Barouch said news outlets are focusing on whether J&J recipients may turn to an mRNA vaccine to boost immunity. But some recipients of Pfizer and Moderna vaccines may benefit from switching to J&J to broaden their immune responses, he said. His hospital is studying fully vaccinated Pfizer recipients who volunteered to receive a J&J booster. Barouch said he hopes to have results soon.

Dr. Ofer Levy, director of the Precision Vaccines Program at Boston Children’s Hospital and a member of the FDA advisory panel that cleared Moderna and J&J boosters, said other factors continue to make all three vaccines viable.

He said mRNA boosters might be a better choice for young women who are concerned about rare cases of blood clots linked to the J&J vaccine. A J&J booster, on the other hand, might be better suited for young men concerned about myocarditis, an inflammation of the heart muscle associated with the mRNA vaccines in rare instances.

And then there’s the challenge and cost of keeping the mRNA vaccines frozen, an advantage for the J&J shot in poor countries. Levy said his research laboratory at Children’s Hospital has a freezer set to minus-80 degrees Celsius. The freezer cost about $20,000, not including the expense of running a backup power supply and an alarm in case there’s a malfunction.

About 25 million J&J doses have gone to countries that the World Bank classifies as low income, according to a recent New York Times report. In contrast, only 8.4 million Pfizer doses and about 1 million Moderna doses have gone to those countries.

“Having a range of vaccines with different characteristics makes sense,” Levy said. “I wouldn’t say J&J is down for the count.”

Jonathan Saltzman can be reached at jonathan.saltzman@globe.com.