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Russians Publish Early Coronavirus Vaccine Results - The New York Times

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On Friday, a team of Russian scientists published the first report on their Covid-19 vaccine, which had been roundly criticized because of President Vladimir Putin’s decision last month to approve it before clinical trials had proved it safe and effective.

In a small group of volunteers, the scientists found that the vaccine produced a modest level of antibodies against the coronavirus, while causing only mild side effects. The research has not yet shown, however, whether people who are vaccinated are less likely to become infected than those who are not.

In August, Mr. Putin announced with great fanfare that the vaccine — called Sputnik V — “works effectively enough” to be approved. He declared its approval to be a “very important step for our country, and generally for the whole world.”

But vaccine developers denounced the decision, observing that no data had been published on the vaccine. In addition, the critics pointed out, the Russian scientists had yet to run a large trial of tens of thousands of people, which is required to demonstrate that a vaccine works.

The new paper, published in the Lancet, contains the first batch of public data from Sputnik V’s clinical trials. Independent scientists were impressed by the rigor of the work.

“The science looks like it was done impeccably well,” said Naor Bar-Zeev of the Johns Hopkins Bloomberg School of Public Health, who is the co-author of a commentary on the new paper. Still, he cautioned that no one will know if Sputnik V is safe and effective until the larger trials are completed.

“We should welcome a Russian vaccine if it’s successful, and we should welcome other vaccines if they’re successful,” Dr. Bar-Zeev said. “But they should all be equally rigorously evaluated.”

Researchers at the Gamaleya Research Institute in Moscow used a design for the vaccine that they had previously developed and tested for MERS, a disease caused by another coronavirus.

The Sputnik V vaccine stimulates the immune system by coaxing a person’s cells to make a protein normally found on the coronavirus that causes Covid-19. The researchers loaded the gene for this viral protein into a second virus, called an adenovirus.

When injected into the arm, the adenovirus slips into muscle cells. It has been genetically engineered so that it cannot make copies of itself or cause illness. But once it delivers the coronavirus gene into a cell, the cell starts making the protein.

Similar adenovirus-based vaccines are also being tested by several other teams, including AstraZeneca, CanSinoBio and Johnson & Johnson.

Each team is testing a different strain of adenovirus. Unlike the rest, the Russian team is combining two adenoviruses into one vaccine. For their initial clinical trial, the Gamaleya researchers gave volunteers an initial shot of an adenovirus called Ad26, and then, three weeks later, a shot of one known as Ad5.

Credit...Yuri Kochetkov/EPA, via Shutterstock

In the Lancet paper, the researchers said that they tested the vaccine on hamsters and monkeys. They claimed the animals were protected against the coronavirus without any harmful side effects but did not present any data about these studies in their new paper.

The trial they ran on human volunteers was what’s known as a Phase 1 / 2 trial. It was small: Only 40 volunteers received the full vaccine with both kinds of adenoviruses. No one received a placebo.

By comparison, the Chinese firm CanSinoBio ran a Phase 1 / 2 trial that included 382 people who received the vaccine and another 126 who were given a placebo.

The Russian vaccine produced mild symptoms in a number of subjects, the most common of which were fevers and headaches. Other adenovirus-based vaccines have produced similar side effects.

“You expect to have some symptoms — that’s normal,” Dr. Bar-Zeev said.

The researchers found that volunteers who received the full vaccine produced antibodies that could block the virus from replicating in cells.

To gauge the performance of their vaccine, the Russian researchers compared the level of antibodies with samples taken from people who had recovered from natural infections of Covid-19. Convalescent plasma, as these samples are known, contain antibodies to the virus that people make on their own.

In the paper, the researchers said that vaccinated people had the same levels of antibodies as those found in convalescent plasma.

Akiko Iwasaki, an immunologist at Yale University who was not involved in the study, said the vaccine produced “good antibody levels in all volunteers.”

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In their paper, the authors said that the levels of neutralizing antibodies produced by their vaccine were lower than those reported for vaccines made by AstraZeneca and Moderna, two of the candidates furthest along in clinical trials.

But in a news release, the Gamaleya Institute implied that its vaccine was superior to AstraZeneca’s. It said that the level of antibodies from vaccinated volunteers was “1.4-1.5 times higher than the level of antibodies of patients who had recovered from Covid-19.”

AstraZeneca, they claimed, only produced antibody levels equal to that in convalescent plasma.

It is not clear why the paper presents a different picture. The authors of the study did not respond to a request for comment.

John Moore, a virologist at Weill Cornell Medicine in New York who was not involved in the study, said that it was too early to make any meaningful comparisons among the various Covid-19 vaccines. Each team uses different tests to measure antibody levels. And each group of recovered patients they study for convalescent plasma may have different levels of antibodies.

“We have long been suffering from the apples-versus-oranges scenario, but now we’re into fruit salad territory, and it drives me bananas trying to figure it all out,” he said.

One thing is clear, however: No Phase 1 / 2 trial can demonstrate protection against Covid-19.

That requires a so-called Phase 3 trial, in which a large number of volunteers are given either a vaccine or a placebo. A Phase 3 trial can also reveal harmful side effects missed by small preliminary studies.

In their paper, the Russian scientists wrote that they got approval on Aug. 26 to run a Phase 3 trial on 40,000 people. There are seven other vaccines currently in these late-stage trials. Johnson & Johnson is expected to start its own Phase 3 trial later this month, and Novavax is expected to start its own in October, bringing the total to 10.

Phase 3 trials can take months to yield clear results, Dr. Bar-Zeev said, and even then they have to be carefully reviewed before any decision is made about using a vaccine widely.

“Yes, we all want a vaccine, but we don’t want to make a mistake,” he said. “So hang in there and wait, so we know what we’re getting into.”

Andrew Kramer contributed reporting from Moscow.

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