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The first vaccine that wasn’t Russia approves a coronavirus immunization, but a lack of clinical trials means those getting inoculated are rolling the dice

Source: Meduza

Russian news headlines

What prompted these reports?

On Tuesday, August 11, during a teleconference with Russian Health Minister Mikhail Murashko, Vladimir Putin noted that Russia’s prototype vaccine “works well enough, forms stable immunity, and has passed all the necessary checks.” Murashko then told the president: “Allow me to report that the state has registered the first vaccine against the novel coronavirus infection.”

This wasn’t news for Putin, who promptly revealed that one of his own daughters has already been inoculated with Russia’s new vaccine. “After the first injection, she had a temperature of 38 [degrees Celsius, 100.4 degrees Fahrenheit] and the next day it was a little over 37 degrees [98.6 degrees Fahrenheit] and that was it. Her temperature rose a bit after the second shot, too, but then it went back down. She’s feeling good,” said Putin.

What’s this vaccine Putin is talking about?

This is the vaccine created by scientists at the Gamaleya Research Institute. In late July, to learn more about this project, Meduza interviewed Denis Logunov, the deputy research director leading the group that developed the vaccine.

Named “Sputnik V,” the two-vector (two-staged) vaccine comprises one shot of human adenovirus type 26 and, administered three weeks later, one shot of human adenovirus type 5 (both containing the SARS-CoV-2 S protein gene). In late July, Logunov told Meduza that his team measured better immune responses to vaccines using different vectors, whereas booster shots that rely on the same vector sometimes lead to weaker immunity that fades after 3–6 months.

Russia isn’t betting the farm on Sputnik V. Scientists there are still developing other types of coronavirus vaccines, as well. Around the world, researchers are working on many kinds of vaccines against the coronavirus — some very similar to what Russia has created and some radically different.

Is this really the world’s first registered coronavirus vaccine?

No. Back on June 29, a vaccine developed by the biotech firm “CanSino Biologics” received approval for military use in China. Like Sputnik V, it uses the adenovirus serotype 5. When speaking to President Putin, Health Minister Mikhail Murashko was clearly aware that Russia’s vaccine will be compared to the one developed in China, but he emphasized that Russia is the first country to approve a coronavirus vaccine “in full.”

In fact, Russia’s vaccine has received the same limited “provisional approval” already awarded to the Chinese drug. In this sense, the two vaccines are the same. The approval issued to the Gamaleya Research Institute expires on January 1, 2021. Based on plans released by the Russian Direct Investment Fund, which is financing the project, the only difference between the approval conditions in Russia and China is which patients will be inoculated first: in Russia, it will be doctors and teachers, not soldiers. 

The Russian vaccine’s provisional approval was issued under conditions established by Government Decree 441 concerning medicines needed in emergencies and against dangerous diseases. This is the regulatory measure that allows limited approval (effective only until the end of the year) of treatments on the basis of preclinical studies alone (in other words, animal tests). For vaccine developers, however, these conditions still require large-scale Phase III trials that typically involve hundreds or thousands of human test subjects. Denis Logunov told Meduza that these trials for his team’s vaccine should begin soon. If the results of the large-scale study fail to confirm the vaccine’s effectiveness, provisional approval could be revoked.

So Russia’s vaccine is at what stage of development exactly?

It’s still at the first stage. Around the world, several other drug manufacturers are already significantly further ahead in their development of a coronavirus vaccine. This includes Moderna, Pfizer-BioNTech, Oxford University, AstraZeneca, the Wuhan Institute of Biological Products (Sinopharm), and Sinovac, as well as CanSino Biologics. These researchers have already begun Phase III trials, while the Gamaleya Research Institute is only just starting such tests.

The paucity of information available about Russia’s vaccine research is another ignoble distinction. Around the world, most foreign scientists working on a coronavirus vaccine have published at least some of their trial results in peer-reviewed scientific journals. In Russia, the Gamaleya Research Institute has yet to share with the expert community any details about its vaccine tests.

So far, Sputnik V has only been administered to two groups of 38 healthy volunteers and these patients are still under observation. This isn’t much. Limited testing like this is typical for Phase-I trials when researchers are evaluating a drug’s minimum safety. During Phase II, researchers first conduct an immunogenicity study (to confirm that the vaccine produces the needed immune response) and determine the necessary dosage. It’s not until Phase III, when the vaccine is compared to a placebo, that scientists can establish the immunization’s effectiveness. In other words, researchers don’t know until completing the third round of tests if their vaccine actually protects against severe infections of the disease they’re fighting. 

According to records published by the U.S. National Library of Medicine, the team at the Gamaleya Research Institute has already confirmed its vaccine’s safety and immunogenicity, which is why these scientists now say they’ve combined Phase I and II testing. But these trials involved incomparably fewer test subjects than even initial testing conducted by other drug manufacturers. (For example, before Phase III, Oxford University tested its vaccine on hundreds of volunteers.) This means that researchers in Russia simply haven’t had the opportunity to “catch” any infrequent, albeit entirely possible, dangerous side effects, no matter how good their vaccine actually is.

Some have defended the accelerated approval of Russia’s coronavirus vaccine by pointing out that its developers had a headstart because they were already working on a vaccine against the Middle East Respiratory Syndrome (MERS), but it’s worth remembering that this vaccine still needs additional clinical trials, as well.

What do we know about Sputnik V’s safety and effectiveness (other than the fact that Putin’s daughter received it and survived)? 

Very little. There are two reasons for that.

First, and this can’t be overstressed, the Gamaleya Research Institute has failed to publish the details of its vaccine trials in any scientific journals, despite promises to do this. Sharing such test results is standard practice in the expert community and many others working on a coronavirus vaccine have already released their preliminary data. Almost everything we know about Russia’s vaccine (which animals underwent preclinical studies, what immunological tests were carried out, and so on) comes from Denis Logunov’s July 23 interview with Meduza. According to a website launched the same day Sputnik V was granted provisional approval, the Gamaleya Research Institute will publish its data later this month.

Second, it’s important to understand that the developers themselves won’t know how effective their vaccine is at producing an immune response until full-fledged Phase-III trials. In fact, drugs often fail at this stage of testing. It is fundamentally impossible to verify Sputnik V’s effectiveness on the basis of the tests conducted so far.

So nothing has actually changed, despite Putin’s announcement?

The vaccine’s availability has changed. Sputnik V will now be obtainable not just by clinical trial subjects but also select groups of people who will not be required to sign certain paperwork or maintain volunteer journals. Neither will they be protected by the World Media Association’s Helsinki Declaration on Ethical Principles for Medical Research Involving Human Subjects, and the Gamaleya Research Institute won’t be responsible for monitoring their condition or including their health information in their research. In other words, these individuals will be getting vaccinated at their own risk and there will be no clinical study of what happens to them.

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