Data fuels debate over whether J&J single dose Covid vaccine will be sufficient



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Johnson & Johnson released the first updated data on its Covid-19 vaccine on Wednesday, showing that it provided participants in a clinical trial with at least some immunity after a dose.

The data, published in the New England Journal of Medicine, only hints at a tantalizing question: Could the vaccine, given as a single injection, work as well as vaccines that US regulators have already licensed, which are administered in two?

In the study, participants had neutralizing antibodies, measured in a unit called the geometric mean titer, from 224 to 354, on day 29 after their first dose of vaccine; these levels reached 288 to 488 on day 57. These levels may be sufficient to produce immunity. But there was a big benefit to giving the participants a booster dose. It doubled or tripled their levels of neutralizing antibodies. The question is whether the levels of antibodies induced by the first dose are indeed sufficient, or whether there are other types of immunity stimulated by the vaccine which lead to protection.

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“Just because the neutralizing response is higher doesn’t mean it’s more effective,” said Paul Offit, director of the Vaccine Education Center at Children’s Hospital of Philadelphia. “It may be that the immune response induced by the first dose is sufficient and more is not necessarily better.”

The answer to the question will of course come from the results of the Phase 3 clinical trials. Carlos del Rio, a distinguished professor of medicine at Emory University’s School of Medicine, said: “The proof is in the pudding.

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A third licensed vaccine – and a vaccine that could be delivered in a single dose – could help reshape the fight against the Covid-19 pandemic, even if supplies are expected to be limited for some time.

“Part of the complication we have is this two-dose deal,” del Rio said. “If we can have a single dose vaccine, the J&J vaccine would undoubtedly become the vaccine of choice for the world.”

Two phase 3 studies are underway. A study of 40,000 volunteers on the single-dose vaccine, conducted in the United States, is expected to be read in the next two weeks. A second, equally large study is conducted using the same vaccine given in two doses, each given 57 days apart, in case the vaccine does not work in a single dose regimen or if there is would have other advantages, such as the durability of the vaccine. vaccine, to administer a second dose.

A previous version of the article published in NEJM was posted in September on a pre-print server, meaning it had not been peer reviewed. But there is new data on the safety and durability of the vaccine in the current document, which includes information on the safety of the vaccine, the duration of immune responses, and the effect of adding a second dose to the drug. first.

Del Rio is optimistic. He points out that after a dose of the current vaccines – one made by Pfizer and its partner, BioNTech, and one made by Moderna – only 60% of participants appeared to have neutralizing antibody levels against SARS-CoV-2, the virus that causes Covid19. With the J&J vaccine data in the NEJM, he said, that figure appears to be 90%. Del Rio was an investigator in the Moderna trial.

But Anna Durbin, a professor at the Johns Hopkins Bloomberg School of Public Health, was less confident about the levels of protection. In particular, she was skeptical that a single-dose vaccine would suffice for older adults, who don’t always develop as strong an immune response as younger people.

“I think it was a bit of a gamble to choose the single dose, and I think it was very responsible for the company to look at a two-dose regimen and a single-dose regimen,” Durbin said, one researcher in the Pfizer vaccine trials and another testing a vaccine made by AstraZeneca.

Johan Van Hoof, global head of J&J’s vaccines division, said animal data, which had shown strong protection on a single-dose basis, and data made available on Wednesday, gave J&J confidence required to attempt a single dose trial. But part of the reason, he said, was the need for a single-dose vaccine during a pandemic.

The World Health Organization, Van Hoof said, stresses that the ideal profile for a pandemic vaccine is different from that in normal times.

“The difference is that for use in an epidemic setting, where you [largest] vaccination campaign, there are huge advantages to opting for a single dose, although there will eventually be a trade-off in terms of durability or protection, ”said Van Hoof.

If the test result, expected in the coming weeks, is positive, the data will be sent to the Food and Drug Administration, setting up a possible emergency use authorization in February. But then there will be the question of how quickly the vaccine can be made. On Tuesday, in a call with reporters, Moncef Slaoui, the outgoing head of the government’s Operation Warp Speed ​​program, said the ramp-up could take time.

He said there would be “one-digit million” doses available in the second half of February, and efforts were being made to increase that number. There would be more in March, and many more in April, Slaoui predicted.

Johnson & Johnson said without regulatory approval it was too early to come up with month-to-month estimates on how many doses are available.

“We have started production of our vaccine candidate and are confident in our ability to meet our 2021 procurement commitments signed with governments, and plan to share more details once some of these milestones have been completed,” he said. the company said in a statement.



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