Yesterday, the people behind Russia’s leading vaccine, termed Sputnik V, issued a preliminary analysis of its function. The news was quite good: while the trial is ongoing and final results will have to wait, the interim data suggests that the vaccine could be over 90 percent effective.
Sputnik V is based on similar technology to the vaccines being developed by Johnson & Johnson and the Oxford/AstraZeneca collaboration. Strikingly, however, the preliminary efficiency is quite a bit higher than those vaccines are showing, and it’s not clear how the Sputnik-specific features could account for the difference.
The results come out of a Phase III clinical trial involving roughly 21,000 participants being run in Moscow. Participants were all over the age of 18, hadn’t received other vaccinations recently, weren’t pregnant or drug users, and met a number of other criteria. PCR-based SARS-CoV-2 tests were performed at enrollment, and participants were also tested for the presence of antibodies against the virus.
While the data gathering was integrated with the Russian health system—which allowed researchers to obtain data from any participant who got health care within the Moscow area—the trial itself was run by a commercial third party based in the Netherlands.
The participants were divided so that three times as many received the vaccine instead of a placebo. This assignment was randomized, and everyone involved was kept in the dark about who got what. While the full trial will continue for several more months, the researchers took advantage of the fact that the vaccine requires two doses separated by 21 days to do an interim analysis of how effective the first dose was. So researchers repeated the PCR and antibody tests, and they checked for its efficacy after a single dose.
The results were remarkably good. There were 16 cases among those who had received the vaccine, compared to 62 cases among those who got a placebo. But remember there were three times as many people in the vaccine group, which makes the effectiveness even higher; the researchers calculated it at just over 90 percent. None of the people who received the vaccine had cases that hit the researchers’ definition of moderate or severe, while 20 people in the placebo group did. This suggests that the vaccine also lowers the chances of severe illness (something that’s been seen with other vaccines).
At 21 days, nearly all of those who received the vaccine had antibodies against SARS-CoV-2, as you’d expect. But 15 percent of those in the placebo group also had antibodies against the virus, suggesting that they’d had asymptomatic cases in the mean time. Based on the trial’s protocol, these weren’t counted as COVID-19 cases for the purpose of the statistics.
A number of people had already been identified as having SARS-CoV-2 ahead of the 21-day time point, and they weren’t included in the analysis that suggested a 90 percent efficacy. That’s because these infections could have started before the vaccine had a chance to generate any significant immune response. If these are included, however, the efficacy of the vaccine drops a bit, to 73 percent.
Complications, medical and otherwise
There was one death each in the vaccine and placebo groups due to random events in the first 21 days of the study. And two people who were vaccinated developed severe COVID-19 within a week of the vaccination and eventually died. Due to the timing of the onset of symptoms there, the researchers estimate that the deceased were probably already infected when they were vaccinated, but the virus hadn’t built up to levels that were detectable via PCR.
Adverse effects were typical of those caused by effective vaccines: fevers, muscle aches, and fatigue were common. When more serious adverse events were considered, however, they were more common in the placebo group (0.4 percent) than in the vaccine recipients (0.3 percent).
So overall, this looks great. In fact, it looks oddly great.
As mentioned above, the Sputnik V vaccine uses the same technology tried by other companies: it places a key coronavirus protein into a harmless cold virus named adenovirus. The unique feature of Sputnik V is that it used two doses, with different strains of adenovirus in each dose. This limits the chance of the immune reaction being focused on the adenovirus itself, instead of the coronavirus protein it carries.
But that advantage wouldn’t be at play with a single dose, meaning we might expect similar effectiveness to that seen from the two other adenovirus-based vaccines. In fact, given that the immune response is likely to still be ramping up at 21 days, we’d probably expect to see reduced effectiveness from any vaccine using the study protocol done here. Yet Sputnik V seems to be significantly more effective than the offerings of Johnson & Johnson or AstraZeneca.
Was data fudged?
On its own, that would be unexpected. But the results are arriving after a somewhat bizarre history for Sputnik V. Concerns include suggestions of manipulated data in the paper describing the Phase I trials of the vaccine, along with Russia starting widespread use of the vaccine ahead of the clinical trial data. Russia also went on to approve a second untested vaccine for good measure. So there’s certainly a fair number of reasons to be skeptical of Russia’s vaccine approach by this point.
Still, given the reasonable successes generated by other adenovirus-based vaccines, don’t be surprised if Sputnik V works. And there’s still the prospect that using two different virus strains will make the vaccine more effective than others based on this technology. But we’ll have to wait for the full trial data to know whether that’s the case—along with some clear answers about the odd history of these trials.
The Lancet, 2021. DOI: 10.1016/S0140-6736(21)00234-8 (About DOIs).