Johnson & Johnson published updated early data on its Covid-19 vaccine Wednesday, showing that it provided participants in a clinical trial with at least some immunity after one dose.
The data, published in the New England Journal of Medicine, offer only hints to a tantalizing question: Could the vaccine, given as a single shot, perform as well as the vaccines that U.S. regulators have already authorized, which are given as two?
In the study, participants had neutralizing antibodies, measured in a unit called a geometric mean titer, of 224 to 354, on day 29 after their first vaccine dose; those levels reached 288 to 488 by day 57. These levels could be enough 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 antibody levels induced by the first dose are indeed enough, or if there are other types of immunity spurred by the vaccine that lead to protection.
“Just because it’s higher in neutralizing response doesn’t necessarily mean it’s more efficacious,” said Paul Offit, director of the Vaccine Education Center at the Children’s Hospital of Philadelphia. “It may be that the immune response induced by the first dose is enough and that more is not necessarily better.”
The answer to the question, of course, will come from Phase 3 clinical trial results. Said Carlos del Rio, a distinguished professor of medicine at the Emory University School of Medicine: “The proof is in the pudding.”
A third authorized vaccine — and one that could be given 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 vaccine that is a single dose, the J&J vaccine would become, without doubt, the vaccine of choice for the world.”
There are two Phase 3 studies running. A 40,000-volunteer study of the one-dose vaccine, conducted in the U.S., is set to read out in the next two weeks. A second, equally big study is being conducted using the same vaccine given as two doses, each administered 57 days apart, in case the vaccine does not prove effective in a one-dose regimen or there are other advantages, such as the durability of the vaccine, to giving a second dose.
A previous version of the paper published in NEJM was released in September on a preprint server, meaning it had not been peer-reviewed. But there are new data on the safety and durability of the vaccine in the current paper, which includes information on the safety of the shot, the duration of immune responses, and the effect of adding a second dose to the first.
Del Rio is optimistic. He points out that after one dose of the current vaccines — one made by Pfizer and its partner, BioNTech, and another made by Moderna — only 60% of participants appeared to have neutralizing antibody levels against SARS-CoV-2, the virus that causes Covid-19. With J&J vaccine data in 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 a one-dose vaccine would be enough for older adults, who don’t always mount as strong an immune response as younger people.
“I think it was a bit of a gamble to go with the single dose, and I think it was very responsible of the company to look at a two-dose regimen and a one-dose regimen,” said Durbin, an investigator in trials of the Pfizer vaccine and another testing a vaccine made by AstraZeneca.
Johan Van Hoof, the global head of J&J’s vaccine division, said that both animal data, which had shown strong protection based on a single dose, and data made available on Wednesday, had given J&J confidence to attempt a one-dose trial. But part of the reason, he said, was the need for a one-dose vaccine in a pandemic.
The World Health Organization, Van Hoof said, points out that the ideal profile of a pandemic vaccine is different from one during normal times.
“The difference there is that for use in an epidemic setting, where you go for the [largest] vaccination campaign, there are huge advantages in going with a single dose, even if there will eventually be some trade-off eventually in terms of durability or protection,” Van Hoof said.
If the trial result, expected in the next few weeks, is positive, the data will be submitted to the Food and Drug Administration, setting up a possible emergency use authorization in February. But then there will be the question of how fast the vaccine can be manufactured. On Tuesday, on 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 “single digit million” doses available in the second half of February, and that efforts were being made to make that number higher. There would more in March, and much more in April, Slaoui predicted.
Johnson & Johnson said that, without regulatory approval, it was too soon to offer month-by-month estimates on the number of doses available.
“We have begun production of our vaccine candidate and are confident in our ability to meet our 2021 supply commitments signed with governments, and we expect to share more detail after some of these steps are achieved,” the company said in a statement.