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One Dose of J.&J. Vaccine Is Ineffective Against Delta, Study Suggests

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The coronavirus vaccine made by Johnson & Johnson is much less effective against the Delta and Lambda variants than against the original virus, according to a new study posted online on Tuesday.

The findings add to evidence that the 13 million people inoculated with the J.&J. vaccine may need to receive a second dose — ideally of one of the mRNA vaccines made by Pfizer-BioNTech or Moderna, the authors said.

But the conclusions are at odds with those from smaller studies published by Johnson & Johnson earlier this month suggesting that a single dose of the vaccine is effective against the variant even eight months after inoculation.

The new study has not yet been peer reviewed nor published in a scientific journal, and relied on laboratory experiments. But it is consistent with observations that a single dose of the AstraZeneca vaccine — which has a similar architecture to the J.&J. vaccine — shows only about 33 percent efficacy against symptomatic disease caused by the Delta variant.

“The message that we wanted to give was not that people shouldn’t get the J.&J. vaccine, but we hope that in the future, it will be boosted with either another dose of J.&J. or a boost with Pfizer or Moderna,” said Nathaniel Landau, a virologist at N.Y.U.’s Grossman School of Medicine, who led the study.

Other experts said the results are what they would have expected, because all of the vaccines seem to work better when given in two doses. “I have always thought, and often said, that the J.&J. vaccine is a two-dose vaccine,” said John Moore, a virologist at Weill Cornell Medicine in New York.

Dr. Moore pointed to several studies in monkeys and people that have shown greater efficacy with two doses of the J.&J. vaccine, compared with one dose. He said the new study was particularly credible because it was published by a team with no ties to any of the vaccine manufacturers.

But the data from the new study “do not speak to the full nature of immune protection,” said Seema Kumar, a spokeswoman for J.&J. Studies sponsored by the company indicate that the vaccine “generated strong, persistent activity against the rapidly spreading Delta variant,” she said.

The Delta variant is the most contagious version yet of the coronavirus. It accounts for 83 percent of infections in the United States, Dr. Rochelle Walensky, director of the Centers for Disease Control and Prevention, said at a Senate hearing on Tuesday.

The variant may also be mainly responsible for a recent rise in infections: Although they are still low relative to last winter, cases are rising in all 50 states, and hospitalizations are increasing in nearly all of them. In the two weeks ending on Tuesday, the nation averaged 268 deaths per day.

Delta may cause more breakthrough infections than earlier forms of the virus, but more than 99 percent of the hospitalizations and deaths are occurring among unvaccinated people. Rates of immunization in the country have stalled, with just under 60 percent of adults fully protected against the virus.

Several studies have suggested that the mRNA vaccines made by Pfizer-BioNTech and Moderna will maintain their efficacy against the coronavirus, including all variants identified so far. One recent study showed, for example, that the vaccines trigger a persistent immune reaction in the body that may protect against the coronavirus for years.

But evidence on the J.&J. vaccine has been limited, because it was rolled out later than the mRNA vaccines. Most studies of effectiveness of the coronavirus vaccines were conducted at medical centers and hospitals that relied on samples from staff members who received the mRNA vaccines.

The J.&J. vaccine has also been dogged by reports of blood clots and a rare neurological syndrome, as well as problems with contamination at a manufacturing plant in Baltimore.

Small studies published by researchers affiliated with J.&J. suggested that the vaccine was only slightly less effective against the Delta variant than against the original virus, and that antibodies stimulated by the vaccine grew in strength over eight months.

Dr. Landau’s team would probably have seen a similar increase in the vaccine’s potency if they had looked at the data over time, said Dr. Dan Barouch, a virologist at Beth Israel Deaconess Medical Center in Boston. The data on the J.&J. vaccine’s strength against the Delta variant at Day 29 is not much different from those reported in his own study, Dr. Barouch said.

“Fundamentally I don’t see that there’s any discordance,” he said. “The question is that of kinetics, it’s not just magnitude, because immune responses are not static over time.” The new study also did not consider other components of immune defense, he added.

Dr. Landau and his colleagues looked at blood samples taken from 17 people who had been immunized with two doses of an mRNA vaccine and 10 people with one dose of the J.&J. vaccine.

The J.&J. vaccine started out with a lower efficacy than the mRNA vaccines and showed a bigger drop in efficacy against the Delta and Lambda variants. “The lower baseline means that what’s left to counter Delta is very weak,” Dr. Moore said. “That is a substantial concern.”

Very few vaccines are given as a single dose, because the second dose is needed to amp up antibody levels, noted Akiko Iwasaki, an immunologist at Yale University. People who were inoculated with the J.&J. vaccine “are relying on that primary response to maintain high levels of antibodies, which is difficult, especially against the variants,” she said.

Boosting immunity with a second dose should raise the antibody levels high enough to counter the variants, she said.

Turning to an mRNA vaccine for the second shot, rather than another J.&J. shot, may be better: Several studies have shown that combining one dose of the AstraZeneca vaccine with a dose of the Pfizer-BioNTech or Moderna vaccines kicks up the immune response more effectively than two doses of AstraZeneca.

The Food and Drug Administration has said “Americans who have been fully vaccinated do not need a booster shot at this time,” and the agency is unlikely to change its recommendations based on laboratory studies. But the new data should prompt the F.D.A. to revisit its recommendations, Dr. Landau said: “I hope that they read our paper and think about it.”



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